Universidad de Panamá

CONTEXT: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. OBJECTIVE: The main objective of this article is to present the research behind the new definition. METHODS: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. RESULTS: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. CONCLUSION: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span.

Abstract Systematic assessments of species extinction risk at regular intervals are necessary for informing conservation action 1,2 . Ongoing developments in taxonomy, threatening processes and research further underscore the need for reassessment 3,4 . Here we report the findings of the second Global Amphibian Assessment, evaluating 8,011 species for the International Union for Conservation of Nature Red List of Threatened Species. We find that amphibians are the most threatened vertebrate class (40.7% of species are globally threatened). The updated Red List Index shows that the status of amphibians is deteriorating globally, particularly for salamanders and in the Neotropics. Disease and habitat loss drove 91% of status deteriorations between 1980 and 2004. Ongoing and projected climate change effects are now of increasing concern, driving 39% of status deteriorations since 2004, followed by habitat loss (37%). Although signs of species recoveries incentivize immediate conservation action, scaled-up investment is urgently needed to reverse the current trends.

When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.

Most eukaryotic organisms are arthropods. Yet, their diversity in rich terrestrial ecosystems is still unknown. Here we produce tangible estimates of the total species richness of arthropods in a tropical rainforest. Using a comprehensive range of structured protocols, we sampled the phylogenetic breadth of arthropod taxa from the soil to the forest canopy in the San Lorenzo forest, Panama. We collected 6144 arthropod species from 0.48 hectare and extrapolated total species richness to larger areas on the basis of competing models. The whole 6000-hectare forest reserve most likely sustains 25,000 arthropod species. Notably, just 1 hectare of rainforest yields >60% of the arthropod biodiversity held in the wider landscape. Models based on plant diversity fitted the accumulated species richness of both herbivore and nonherbivore taxa exceptionally well. This lends credence to global estimates of arthropod biodiversity developed from plant models.

A new microplate assay for cytotoxicity testing using A. salina has been developed and shown to give results comparable to a previously published test-tube method. The assay reliably detected all of the compounds toxic to KB cells in a series of 21 pharmacologically active agents, except for two which require metabolic activation in man. Four quassinoids with cytotoxic and antiplasmodial activity were also toxic to the brine shrimp while quassin itself was inactive in all three systems. It is proposed that this assay provides a convenient means by which the presence of cytotoxic quassinoids may be detected during the fractionation of plant extracts.

Abstract Many insect species are under threat from the anthropogenic drivers of global change. There have been numerous well‐documented examples of insect population declines and extinctions in the scientific literature, but recent weaker studies making extreme claims of a global crisis have drawn widespread media coverage and brought unprecedented public attention. This spotlight might be a double‐edged sword if the veracity of alarmist insect decline statements do not stand up to close scrutiny. We identify seven key challenges in drawing robust inference about insect population declines: establishment of the historical baseline, representativeness of site selection, robustness of time series trend estimation, mitigation of detection bias effects, and ability to account for potential artefacts of density dependence, phenological shifts and scale‐dependence in extrapolation from sample abundance to population‐level inference. Insect population fluctuations are complex. Greater care is needed when evaluating evidence for population trends and in identifying drivers of those trends. We present guidelines for best‐practise approaches that avoid methodological errors, mitigate potential biases and produce more robust analyses of time series trends. Despite many existing challenges and pitfalls, we present a forward‐looking prospectus for the future of insect population monitoring, highlighting opportunities for more creative exploitation of existing baseline data, technological advances in sampling and novel computational approaches. Entomologists cannot tackle these challenges alone, and it is only through collaboration with citizen scientists, other research scientists in many disciplines, and data analysts that the next generation of researchers will bridge the gap between little bugs and big data.

The purpose of this document is to update key concepts in the management of postpartum hemorrhage (PPH) and give clear and precise tools to health personnel in low- and middle-income countries (LMICs) to perform evidence-based treatments, with the aim of reducing related maternal morbidity and mortality. Gynecologists, obstetricians, midwives, nurses, general practitioners, and other health personnel in charge of the care of pregnant women with PPH. The recommendations were developed as a synthesis and update of evidence from the literature. They are based on the FIGO Safe Motherhood and Newborn Health Committee (SMNH) guidelines that were published in 20121 and include research and consensus guidelines. For the present document, a bibliographic review was performed, and studies from LMICs and across regions were identified using the search engines PubMed, Medline, Embase, Science Direct, and Google Scholar. According to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, this update does not generate a universal level of evidence. However, each section and the generated conclusions and recommendations use the degrees of evidence that were identified in the bibliographic review. Conceptualization: MFE, AN, GT, EB, WN, DR, IL. Manuscript writing: MFE, AN, GT, TB, EB, WN, DR, IL, EC, SM, RB, GO, JC, IR, MAI, SL, DN. Review and approval of manuscript: MFE, AN, GT, EB, WN, DR. GT reports a research grant from the South African Medical Research Council to fund Sinapi Biomedical to develop the Ellavi UBT and conduct associated research. EB reports part ownership of BioIncept. EC was a member of the Guideline Development Group for the RCOG's PPH Greentop Guideline (2016), and the FIGO Guideline on Placenta Acreta Spectrum (2018). SM reports that Regents, University of California receives a royalty fee from LifeWrap-NASG for the use of the trademark name ("LifeWrap") for a Non-pneumatic Anti-Shock Garment (NASG). TB reports PPH research funded by the Gates Foundation; PPH Implementation efforts funded by RzHC; PPH Implementation efforts funded by UK AID; PPH Implementation efforts funded by Grand Challenges Canada; PPH efforts and research funded by USAID; PPH efforts by Norway Government. Other authors report no conflicts of interest. These FIGO recommendations are not intended to be a sole source of guidance or prescriptive protocol in managing PPH. They are designed to assist stakeholders by providing an evidence-based framework for decision-making in a PPH setting. The clinical judgment of the doctor or other practitioner, in the context of the clinical presentation of the patient and the available resources for diagnosis and treatment, should always inform the choice of clinical procedure and treatment plan. 6.1. Guidelines that address the prevention of postpartum hemorrhage 6.2 Guidelines that address the treatment of postpartum hemorrhage FIGO (International Federation of Gynecology and Obstetrics) is actively contributing to the global effort to reduce maternal death and disability around the world. Its mission statement reflects a commitment to promoting health, human rights, and well-being of all women, especially those at the most significant risk of death and disability associated with childbearing. FIGO provides evidence-based interventions that can reduce the incidence of maternal morbidity and mortality when applied with informed consent. Postpartum hemorrhage (PPH) continues to be the leading cause of maternal morbidity and mortality in most countries around the world. Despite multiple collaborative efforts at all levels, there is still a lack of implementation or adherence to the recommendations for management of PPH when faced with this obstetric emergency. In part, this delay in implementation lies in the lack of information from current evidence and a lack of unification of the multiple guidelines for diagnosis and strategies to control bleeding. To provide clear and practical tools to approach this obstetric emergency, especially for low- and middle-income countries (LMICs), the FIGO Safe Motherhood and Newborn Health Committee (SMNH), supported by a group of experts worldwide, developed this updated review. It aims to provide multiple alternatives for the diagnosis and management of PPH tailored to the resources available at the institutional, local, or regional level. This document reflects the best available evidence, drawn from scientific literature and expert opinion, on the prevention and treatment of PPH in low-resource settings. FIGO believes that the greatest impediment in the adoption of a given strategy is the absence of an effective implementation tool. Health workers at all levels of care (particularly in LMICs) need to have access to appropriate medications1 and training in PPH prevention and management procedures. All attempts should be made to reduce PPH using cost-effective, resource-appropriate interventions. At first, all should be done to avoid PPH and reduce the need for expensive, lifesaving surgical interventions. The routine use of active management of the third stage of labor by all attendants, regardless of where they practice, should be recommended.2 All birth attendants must know how to provide safe care (physiologic management) to prevent PPH in the absence of uterotonic drugs.3 Postpartum hemorrhage (PPH) is an obstetric emergency complicating 1%–10% of all deliveries.1 It continues to be the leading obstetric cause of maternal death.1 In 2015, it was reported to be responsible for more than 80 000 maternal deaths worldwide.1 Its distribution varies across regions, with the highest prevalence of 5.1%–25.7% reported in Africa, followed by North America at 4.3%–13% and Asia at 1.9%–8%.2 The incidence of PPH has also been on the rise,2-5 increasing from 5.1%–6.2% in Canada between 2003 and 2010,3 and from 2.9%–3.2% in the USA between 2010 and 2014.4 FIGO has made several recommendations in the past 20 years for the management and treatment of PPH (Table 1). This document will update the recommendations and discuss new approaches. The lack of consistency in the definition of PPH has been a major limitation to the ability to compare prevalence in different studies (Table 2). Classically, it was defined as quantified bleeding of more than 500 ml for vaginal deliveries and more than 1000 ml for cesarean deliveries, occurring within the first 24 h of delivery.1 However, this definition did not focus on clinical signs and symptoms of hemorrhage, and thus prevented early detection in many cases. Therefore, in 2017, the American College of Obstetricians and Gynecologists (ACOG) changed the definition to blood loss of more than or equal to 1000 ml, or blood loss that was accompanied by signs or symptoms of hypovolemia occurring within 24 h after birth, regardless of the mode of delivery.6 In contrast, the Royal College of Obstetricians and Gynaecologists (RCOG) defines PPH according to the volume of blood lost: minor (between 500 and 1000 ml) and major (>1000 ml).7 However, the volume of estimated blood loss remains unreliable in many cases, and therefore much attention should be directed to the general clinical status of the patient instead.8 Several tools for assessment of blood loss have been used as accurate estimation will directly influence the diagnosis and management of PPH. Many groups cite visual estimation as part of blood loss assessment, but as it has high potential to underestimate hemorrhage, use of additional tools for more objective estimation, such as gravimetric measurement, direct blood collection techniques, and evaluation of clinical parameters, have been proposed.9-17 Recently, some guidelines have incorporated the shock index9, 11, 14, 17 and obstetric early warning systems into their recommendations to evaluate bleeding.11, 14, 17 American College of Obstetricians and Gynecologists (2017) Dutch Society of Obstetrics and Gynecology (2012) >1000 ml regardless of route of delivery Any blood loss that causes hemodynamic instability Federation of Obstetric and Gynaecological Societies of India (2015) French College of Gynaecologists and Obstetricians/French Society of Anesthesiology and Intensive Care (2016) The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (2017) World Health Organization (2012) >500 ml regardless of route of delivery Severe PPH >1000 ml International Federation of Gynecology and Obstetrics (2012) Society of Obstetricians and Gynaecologists of Canada (2018) Vaginal delivery >500 ml, cesarean delivery >1000 ml Any blood loss that has the potential to produce hemodynamic instability >500 ml regardless of the route of delivery PPH mild: 500–1000 ml, moderate: 1000–2000 ml, severe: >2000 ml Uterine atony can be anticipated after prolonged labor particularly with the use of oxytocin, in pregnancies complicated with chorioamnionitis, high parity, general anesthesia, and other factors that lead to uterine overdistension such as multiple fetal gestation, polyhydramnios, and fetal macrosomia.6, 20 Trauma accounts for 15%–20% of cases,21 and is mostly attributed to perineal or cervical lacerations, perineal hematomas, episiotomies, or uterine rupture.6, 20 These occur in the setting of precipitous uncontrolled deliveries or operative vaginal deliveries.6 Retained products of conception can increase the risk of PPH by 3.5 times.22 Risk factors include succenturiate placenta and previous instrumentation.6 Coagulation problems can be divided into inherited, such as von Willebrand diseases, hemophilia, and idiopathic thrombocytopenic purpura, and acquired, such as the use of anticoagulant therapy20 and the occurrence of disseminated intravascular coagulopathy after placental abruption, pre-eclampsia with severe features, intrauterine fetal demise, sepsis, or amniotic fluid embolism.6, 20, 23 Other etiologies include uterine inversion and abnormal placentation. Multimodal strategies have been implemented in high-income countries to control pathologies with high mortality rates such as PPH. These initiatives that involve multiple intervention points and actors have been called "bundles" or intervention packages, which consist of the implementation of a group of interventions as well as multidisciplinary programs that standardize and comprehensively address the management of pathologies.1-6 Bundles represent a selection of existing guidelines and recommendations in a form that aids systematic implementation and a consistency of practice. The California Maternal Quality Care Collaborative (CMQCC) Working Group on obstetrical hemorrhage developed the Improving the Health Care Response to Obstetric Bleeding Toolkit in 2010 to help obstetric providers, clinical staff, hospitals, and healthcare organizations develop methods within their facility for timely recognition and an organized and rapid response to bleeding. In March 2015, version 2.0 was updated with the latest evidence-based changes.6 In 2015, work groups of the National Partnership for Maternal Safety — within the Council on Patient Safety in Women's Health Care that represents all major women's healthcare professional organizations in the USA — developed an obstetric hemorrhage safety bundle. The goal of the partnership was the adoption of the safety bundle by every birthing facility. This consensus bundle is organized into four action domains: readiness; recognition and prevention; response; and reporting and systems learning. There are 13 key elements within these four action domains (Table 3). In 2017, the World Health Organization (WHO) carried out a technical consultation among international maternal health experts to evaluate the development of care bundles for PPH. A total of 730 articles were reviewed and 430 were used for the construction of the theoretical framework of the process. The consultation led to a definition of two care bundles, which are summarized in Table 4. Uterotonic drugs Isotonic crystalloids Tranexamic acid Uterine massage Notes: Initial fluid resuscitation is performed together with intravenous (IV) administration of uterotonics. If IV uterotonics are not available, fluid resuscitation should be started in parallel with sublingual misoprostol or other parenteral uterotonics. If PPH is in the context of placental retention, the placenta should be extracted, and a single dose of antibiotics should be administered. If lacerations are encountered, they should be repaired. Compressive measures (aortic compression or bimanual uterine compression) Intrauterine balloon tamponade Non-pneumatic antishock garment Notes: A continuing dose of uterotonics (e.g. oxytocin diluted in isotonic crystalloids) and a second dose of tranexamic acid should be administered during the application of this bundle. The first response PPH bundle must be implemented at both the primary healthcare and hospital levels. The discussion about the response to refractory PPH bundle raised some controversy. For the first response PPH bundle, the next phase is the development of an implementation strategy, culminating in a model for use at the facility level in LMICs. For the response to refractory PPH bundle, it is a priority to solve pending controversies, including the operational definition of refractory PPH, and to better understand the effectiveness of various uterine balloon tamponade (UBT) devices. FIGO considers that the bundle care approach can improve patient outcomes when adherence to all components is high. Every health system needs to adopt a bundle and there are many available for use. Place the bundle in every maternity hospital and train to all elements of bundle, from arrival on obstetrics service to transfer to higher level of care. Shock refers to a reduction in tissue perfusion, which is insufficient to meet the metabolic requirements of tissues and organs. Insufficient blood flow may be clinically identified as the development of one or more of the following: lactic acidosis, altered mental status, oliguria, and tachycardia. Vital signs monitoring is key to hemodynamic assessment and prompt intervention.1 In healthy pregnant and postpartum women, cardiologic physiologic compensatory mechanisms prevent changes in vital signs until a large volume of blood has been lost (usually >1000 ml). Hence, changes in clinical and vital signs that result from hemorrhage appear late in the process and may not lead to early identification of PPH. This in turn makes it difficult to establish cutoff points to trigger clinical interventions. Moreover, because traditional vital signs change late and are less reliable as triggers for clinical actions, other indicators could help to characterize maternal hypovolemia caused by bleeding.2 Although the use of conventional individual vital signs (pulse and systolic blood pressure) may lack accuracy in the assessment of hypotension, a simple combination of both may transform routine clinical parameters into a more accurate indicator of hypovolemia, such as the shock index (SI). SI is defined as the ratio of heart rate to systolic blood pressure.3, 4 The SI may improve the predictive capability of individual clinical signs, which aids early identification of women at risk of hypovolemia as the result of obstetric causes.5 Moreover, the SI has been proposed as a reliable indicator of adverse maternal outcomes,6 and its values have been set to indicate clinical management.7 However, the association between shock parameters and advanced treatment modalities in severe PPH has yet to be reported. The essential cornerstone of management of PPH involves prompt diagnosis and rapid replacement of lost blood volume, as well as the oxygen-carrying capacity of blood, accompanied by immediate medical and surgical measures to address the underlying cause(s), and hence prevent more loss. To assess the patient's condition, SI has been introduced as a simple and clinically effective vital sign. The SI has been shown to have an inverse linear relationship with left ventricular stroke work in acute circulatory failure. Therefore, a concurrent reduction of left ventricular stroke work (induced by hemorrhage, trauma, or sepsis) was associated with an elevation of the SI and a deterioration in left ventricular mechanical performance. Poor left ventricular function or persistent abnormal elevation of the SI after aggressive therapy and hemodynamic stabilization was associated with increased mortality in critically ill, traumatized patients.8 In obstetric and nonobstetric circumstances, the absence of a significant drop in blood pressure in patients with PPH may mask the actual hypovolemic status due to physiological compensatory mechanisms.9 For that reason, the SI was the only promising marker that indicated the severity of blood loss.2, 5 The SI, together with the rule of 30, are important tools that may aid clinicians in an emergency to determine the amount of blood loss and the degree of hemodynamic instability. Before the fall in systolic blood pressure, heart rate rises to compensate for the blood loss, and thus the SI increases. The rule of 30 is an approximated blood loss of 30% of normal (70 ml/kg in adults, 100 ml/kg throughout pregnancy), defined by a fall of 30% in hematocrit, a fall of 30% in hemoglobin (approximately 3 g/dl), a fall of 30 mm Hg in systolic blood pressure, and a rise in pulse rate by 30 beats per minute.10 It has been shown that an SI ≥0.9 is associated with increased mortality and an SI>1 increases the likelihood of blood transfusion.11, 12 To date, standard obstetric SI has been defined as 0.7–0.9 compared with 0.5–0.7 for the nonpregnant population, taking into account that the hemodynamic changes of pregnancy may delay the recognition of hypovolemia.5 If intravascular volume depletion is suspected, a rapid clinical assessment is required because the patient's clinical condition can deteriorate, leading to the development of hemorrhagic shock rapidly. Proper medical record-taking skills may highlight symptoms associated with shock such as pain and overt blood loss, as well as general malaise, anxiety, and dyspnea. Notably, in settings where few PPH treatment options exist, and in cases of home deliveries, diagnosis and treatment or referral must occur even earlier than in hospital settings to improve outcomes. For that reason, SI may be a valuable threshold in LMICs, where mortality is highest and is often related to delays in complication recognition, transportation, and level of care at the facility.2 A threshold of SI ≥0.9 should be tested to alert community healthcare providers of the need for urgent transfer.13 FIGO considers that the shock index can be a marker of the severity of PPH and can alert teams to hemodynamic instability when its value is greater than 0.9. Guidelines are defined as systematically developed statements that assist practitioners to take decisions about appropriate health care in specific clinical circumstances.1 Over the past decades, many and international PPH guidelines have been developed and part of obstetric clinical around the world. PPH guidelines address (e.g. and treatment of but may in their These are because most of the recommendations are based on clinical and expert There are few available to produce recommendations for the management of PPH due to the emergency of the condition that this of In the absence of guidelines the best available evidence. In resources as well as and of may influence the and some management of third stage of labor is in There is consensus that all women should uterotonics after delivery as it has to reduce PPH has been as the of choice by most but its and route of administration especially when mode of In FIGO recommendations for the prevention of and in updated its for PPH prevention and the use of oxytocin or as the of also the use of or there are no or misoprostol in settings where oxytocin is not available or its be is also when the use of other uterotonics is not due to or to use such as in the context of 13 The Society of Obstetricians and Gynaecologists of Canada has updated its and the use of as a uterotonic for prevention at cesarean delivery or vaginal delivery with one risk The that during cesarean delivery can consist of oxytocin or Other strategies have been proposed in but many no consensus or no clear Table 5 various PPH prevention strategies by different of uterotonics after delivery Uterotonic at the of birth, late and administration of uterotonics after delivery Vaginal 5 may be used in the absence of not Uterine massage is of no for prevention of uterotonics after delivery 5 or or IV At can be performed as as it does not administration of uterotonics after delivery or has no on and placenta delivery or If uterotonics are not 100 or its is to other effective uterotonics Vaginal oxytocin is not available or oxytocin is not available or PPH guidelines a multidisciplinary approach for effective early control of bleeding. should be directed to the specific cause of PPH trauma, and should from the less to the more and A set of measures also to be in most guidelines and consist of of two large IV of monitoring of women, crystalloids and measures to avoid and evaluate the PPH If atony is the most guidelines mechanical such as uterine massage or uterine bimanual with concurrent are the treatment for uterine oxytocin is the and route of but its varies oxytocin to control PPH, guidelines the use of an additional such as or as a uterotonic available for and the guidelines highlight that the use of to PPH is not (Table or in of normal at per oxytocin in of IV fluid at per until hemorrhage If oxytocin is not available or administration is not dose of or every in every be used as in of is with or sublingual than are with than with or can be every to a of is a 100 or IV in ml of IV If it is followed by oxytocin in as a of oxytocin can be administered only If with adverse should not be used as IV not If uterotonics are not or administration of oxytocin may be If uterotonics are 500 in 500 ml IV Initial 100 1000 h or application is use to be as of the World Maternal tranexamic acid an has been incorporated into PPH guidelines around the 13 has updated this and the use of as as within the first 3 h from birth, at a dose of regardless of the route of 13 However, some guidelines not cite or not it in a because their update the that has been in many guidelines is for there is no consensus about its treatment in hemorrhage, guidelines some and more surgical The available guidelines are summarized in Table The most are uterine balloon tamponade uterine and Uterine with is also in some but its use is 5 the use of a with guidelines cite the use of intrauterine with a with a to the lack of evidence, guidelines not these in a and their on the of professional with and clinical UBT is indicated as the treatment of choice when uterine atony is refractory to uterotonics after vaginal delivery as it is less than the other This should be after out products of or vaginal or cervical as a contributing If UBT to control bleeding in these cases, by most by surgical are (Table are to avoid when is The most in guidelines are the most are uterine less and can also be used uterine for atony at vaginal uterotonics or are not Uterine is not than discuss with a second is of the the uterine Research was to evaluate the potential and of this intervention uterine when uterotonics and bimanual uterine massage If balloon system is not available, with treatment for atony to medical and can be associated with less uterine uterine until measures are or when medical therapy for uterine uterine uterine compression does not other with at not Uterine with with not be or left should be for placental the procedure of choice for atony Uterine massage compression of bleeding after uterine

Amphibian populations around the world are experiencing unprecedented declines attributed to a chytrid fungal pathogen, Batrachochytrium dendrobatidis. Despite the severity of the crisis, quantitative analyses of the effects of the epidemic on amphibian abundance and diversity have been unavailable as a result of the lack of equivalent data collected before and following disease outbreak. We present a community-level assessment combining long-term field surveys and DNA barcode data describing changes in abundance and evolutionary diversity within the amphibian community of El Copé, Panama, following a disease epidemic and mass-mortality event. The epidemic reduced taxonomic, lineage, and phylogenetic diversity similarly. We discovered that 30 species were lost, including five undescribed species, representing 41% of total amphibian lineage diversity in El Copé. These extirpations represented 33% of the evolutionary history of amphibians within the community, and variation in the degree of population loss and decline among species was random with respect to the community phylogeny. Our approach provides a fast, economical, and informative analysis of loss in a community whether measured by species or phylogenetic diversity.

The decomposition of plant litter is one of the most important ecosystem processes in the biosphere and is particularly sensitive to climate warming. Aquatic ecosystems are well suited to studying warming effects on decomposition because the otherwise confounding influence of moisture is constant. By using a latitudinal temperature gradient in an unprecedented global experiment in streams, we found that climate warming will likely hasten microbial litter decomposition and produce an equivalent decline in detritivore-mediated decomposition rates. As a result, overall decomposition rates should remain unchanged. Nevertheless, the process would be profoundly altered, because the shift in importance from detritivores to microbes in warm climates would likely increase CO(2) production and decrease the generation and sequestration of recalcitrant organic particles. In view of recent estimates showing that inland waters are a significant component of the global carbon cycle, this implies consequences for global biogeochemistry and a possible positive climate feedback.

ABSTRACT We surveyed the population status of the Neotropical toad genus Atelopus , and document recent catastrophic declines that are more severe than previously reported for any amphibian genus. Of 113 species that have been described or are candidates for description, data indicate that in 42 species, population sizes have been reduced by at least half and only ten species have stable populations. The status of the remaining taxa is unknown. At least 30 species have been missing from all known localities for at least 8 yr and are feared extinct. Most of these species were last seen between 1984 and 1996. All species restricted to elevations of above 1000 m have declined and 75 percent have disappeared, while 58 percent of lowland species have declined and 38 percent have disappeared. Habitat loss was not related to declines once we controlled for the effects of elevation. In fact, 22 species that occur in protected areas have disappeared. The fungal disease Batrachochytrium dendrobatidis has been documented from nine species that have declined, and may explain declines in higher elevation species that occur in undisturbed habitats. Climate change may also play a role, but other potential factors such as environmental contamination, trade, and introduced species are unlikely to have affected more than a handful of species. Widespread declines and extinctions in Atelopus may reflect population changes in other Neotropical amphibians that are more difficult to survey, and the loss of this trophic group may have cascading effects on other species in tropical ecosystems.

Abstract. We evaluate a three‐part hypothesis explaining why gall‐inducing insect species richness is so high in scleromorphic vegetation: (1) persistence of low nutrient status scleromorphic leaves facilitates the galling habit in warm temperate latitudes; (2) favourable colonization sites for gallers result from reduced hygrothermal stress, high phenolics in the outer cortex of the gall, and reduced carnivore and fungal attack in the gall; and (3) in more mesic sites, mortality is high due to carnivore attack and invasion of galls by fungi. Over 280 samples of local species of galling herbivorous insects from fourteen countries on all continents except Antarctica revealed a strong pattern of highest richness in warm temperate latitudes, or their altitudinal equivalents. The peak of galling species richness on the latitudinal gradient from the equator into the Arctic was between 25 to 38° N or S. Galling species were particularly diverse in sclerophyllous vegetation, which commonly had greater than twelve species per local sample. In mesic, non‐sclerophyllous vegetation types the number of galling species was lower with twelve or fewer species present. Many sites in sclerophyllous vegetation supported between thirteen and forty‐six galling species locally, including campina islands in Amazonia, cerrado savanna in central Brazil, the Sonoran Desert in Arizona and Mexico, shrubland in Israel, fynbos in South Africa and coastal scleromorphic vegetation in Australia. At the same latitude, or its elevational equivalent, galling species richness was significantly higher in relatively xeric sites when compared to riparian or otherwise mesic habitats, even when scleromorphic vegetation dominated the mesic sites. The results were consistent with the hypothesis and extend to a more general level the patterns and predictions on the biogeography of gall‐inducing insects.

1 We examined the abundance and distribution patterns of pioneer seeds in the soil seed bank, and of pioneer seedlings in 53 recently formed gaps, in a 50‐ha forest dynamics plot on Barro Colorado Island (BCI), Panama. The aim was to assess the importance of dispersal limitation (failure of seeds to arrive at all sites suitable for their germination) and establishment limitation (failure of seeds having reached a site to germinate successfully and establish as seedlings) in determining patterns of gap occupancy. 2 The abundance of seeds in the soil seed bank was strongly negatively correlated with seed size, but was not correlated with the abundance of reproductive‐sized adult trees in the plot. In contrast, the abundance of pioneer seedlings > 10 cm height in natural gaps was strongly correlated with adult abundance, but was not correlated with seed size. 3 Seedlings were non‐randomly distributed among gaps, but seedling abundance was not directly related to gap size, and there was no evidence of partitioning of the light environment of gaps by small seedlings. Large differences in growth and mortality rates among species were observed after 1 year, and this may result in the gap size partitioning previously found in saplings of the same species. 4 Seedlings of most species, particularly those with large seeds, were relatively more abundant than expected in gaps close to their conspecific adults. Proximity to reproductives, and by inference dispersal limitation, therefore exerts some effect on seedling distribution. None the less, large differences between seed and seedling abundances for some species, and low seedling occupancy rates in some gaps close to adult conspecifics, suggest that seedling emergence probabilities and species‐specific establishment requirements may also be important determinants of local abundance.

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.

Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2 km of distance, 40 m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.

The indigenous Kuna who live on islands in the Panamanian Caribbean were among the first communities described with little age-related rise in blood pressure or hypertension. Our goals in this study were to ascertain whether isolated island-dwelling Kuna continue to show this pattern, whether migration to Panama City and its environs changed the patterns, and whether the island-dwelling Kuna have maintained their normal blood pressure levels despite partial acculturation, reflected in an increased salt intake. We enrolled 316 Kuna participants who ranged in age from 18 to 82 years. In 50, homogeneity was confirmed by documentation of an O+ blood group. In 92 island dwellers, diastolic hypertension was not identified and blood pressure levels were as low in volunteers over 60 years of age as in those between 20 and 30 years of age. In Panama City, conversely, hypertension prevalence was 10.7% and exceeded 45% in those over 60 years of age (P < .01), blood pressure levels were higher in the elderly, and there was a statistically significant positive relationship between age and blood pressure (P < .01). In Kuna Nega, a Panama City suburb designed to maintain a traditional Kuna lifestyle but with access to the city, all findings were intermediate. Sodium intake and excretion assessed in 50 island-dwelling Kuna averaged 135 +/- 15 mEq/g creatinine per 24 hours, exceeding substantially other communities free of hypertension and an age-related rise in blood pressure. Despite partial acculturation, the island-dwelling Kuna Indians are protected from hypertension and thus provide an attractive population for examining alternative mechanisms.

Due to their particular water absorption capacity, hydrogels are the most widely used scaffolds in biomedical studies to regenerate damaged tissue. Hydrogels can be used in tissue engineering to design scaffolds for three-dimensional cell culture, providing a novel alternative to the traditional two-dimensional cell culture as hydrogels have a three-dimensional biomimetic structure. This material property is crucial in regenerative medicine, especially for the nervous system, since it is a highly complex and delicate structure. Hydrogels can move quickly within the human body without physically disturbing the environment and possess essential biocompatible properties, as well as the ability to form a mimetic scaffold in situ. Therefore, hydrogels are perfect candidates for biomedical applications. Hydrogels represent a potential alternative to regenerating tissue lost after removing a brain tumor and/or brain injuries. This reason presents them as an exciting alternative to highly complex human physiological problems, such as injuries to the central nervous system and neurodegenerative disease.

CONTEXT AND OBJECTIVE: Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). DESIGN AND PARTICIPANTS: We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. RESULTS: Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, -0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001). CONCLUSION: Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

BACKGROUND: Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time. DESIGN: Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for the primary analyses which will compare mean levels of nutrients at baseline and over time. Initial commitments to collaboration have been obtained from 21 countries. CONCLUSIONS: This collaborative approach to the collation and sharing of data will enable objective and transparent tracking of processed food composition around the world. The information collected will support government and food industry efforts to improve the nutrient composition of processed foods around the world.

Most hypotheses explaining the general gradient of higher diversity toward the equator are implicit or explicit about greater species packing in the tropics. However, global patterns of diversity within guilds, including trophic guilds (i.e., groups of organisms that use similar food resources), are poorly known. We explored global diversity patterns of a key trophic guild in stream ecosystems, the detritivore shredders. This was motivated by the fundamental ecological role of shredders as decomposers of leaf litter and by some records pointing to low shredder diversity and abundance in the tropics, which contrasts with diversity patterns of most major taxa for which broad-scale latitudinal patterns haven been examined. Given this evidence, we hypothesized that shredders are more abundant and diverse in temperate than in tropical streams, and that this pattern is related to the higher temperatures and lower availability of high-quality leaf litter in the tropics. Our comprehensive global survey (129 stream sites from 14 regions on six continents) corroborated the expected latitudinal pattern and showed that shredder distribution (abundance, diversity and assemblage composition) was explained by a combination of factors, including water temperature (some taxa were restricted to cool waters) and biogeography (some taxa were more diverse in particular biogeographic realms). In contrast to our hypothesis, shredder diversity was unrelated to leaf toughness, but it was inversely related to litter diversity. Our findings markedly contrast with global trends of diversity for most taxa, and with the general rule of higher consumer diversity at higher levels of resource diversity. Moreover, they highlight the emerging role of temperature in understanding global patterns of diversity, which is of great relevance in the face of projected global warming.

This paper describes the development of a novel microfluorimetric assay to measure the inhibition of Plasmodium falciparum based on the detection of parasitic DNA by intercalation with PicoGreen. The method was used to determine parasite inhibition profiles and 50% inhibitory concentration values of known or potential antimalarial drugs. Values for parasite inhibition with known anti-malarial drugs using the PicoGreen assay were comparable with those determined by the standard method based upon the uptake of 3H-hypoxanthine and the Giemsa stain microscopic technique. The PicoGreen assay is rapid, sensitive, reproducible, easily interpreted, and ideally suited for screening of large numbers of samples for anti-malarial drug development.