CUNY School of Law

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2's linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.

While a potential causal factor in Alzheimer's disease (AD), brain insulin resistance has not been demonstrated directly in that disorder. We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway. Reduced insulin responses were maximal at the level of IRS-1 and were consistently associated with basal elevations in IRS-1 phosphorylated at serine 616 (IRS-1 pS⁶¹⁶) and IRS-1 pS⁶³⁶/⁶³⁹. In the HF, these candidate biomarkers of brain insulin resistance increased commonly and progressively from normal cases to mild cognitively impaired cases to AD cases regardless of diabetes or APOE ε4 status. Levels of IRS-1 pS⁶¹⁶ and IRS-1 pS⁶³⁶/⁶³⁹ and their activated kinases correlated positively with those of oligomeric Aβ plaques and were negatively associated with episodic and working memory, even after adjusting for Aβ plaques, neurofibrillary tangles, and APOE ε4. Brain insulin resistance thus appears to be an early and common feature of AD, a phenomenon accompanied by IGF-1 resistance and closely associated with IRS-1 dysfunction potentially triggered by Aβ oligomers and yet promoting cognitive decline independent of classic AD pathology.

BACKGROUND: Major depression is associated with significant disability, morbidity, and mortality. The current study estimated trends in the prevalence of major depression in the US population from 2005 to 2015 overall and by demographic subgroups. METHODS: Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons ages 12 and over (total analytic sample N = 607 520). Past-year depression prevalence was examined annually among respondents from 2005 to 2015. Time trends in depression prevalence stratified by survey year were tested using logistic regression. Data were re-analyzed stratified by age, gender, race/ethnicity, income, and education. RESULTS: Depression prevalence increased significantly in the USA from 2005 to 2015, before and after controlling for demographics. Increases in depression were significant for the youngest and oldest age groups, men, and women, Non-Hispanic White persons, the lowest income group, and the highest education and income groups. A significant year × demographic interaction was found for age. The rate of increase in depression was significantly more rapid among youth relative to all older age groups. CONCLUSIONS: The prevalence of depression increased significantly in the USA from 2005 to 2015. The rate of increase in depression among youth was significantly more rapid relative to older groups. Further research into understanding the macro level, micro level, and individual factors that are contributing to the increase in depression, including factors specific to demographic subgroups, would help to direct public health prevention and intervention efforts.

BACKGROUND: The US Preventive Services Task Force recently recommended screening all adult patients for obesity due in part to the strong association between obesity and numerous chronic diseases. However, how obesity affects health-related quality-of-life (HRQL), particularly for persons without any chronic diseases, is less clear. METHODS: The relationship between obesity and HRQL was examined using data from the 2000 Medical Expenditure Panel Survey. Respondents > or =18 years were classified as underweight, normal weight, overweight, class I obesity, and class II obesity based on their BMI. HRQL was measured by the 12-item Short Form physical and mental summary scores (PCS-12 and MCS-12, respectively) and EuroQol EQ-5D index and visual analogue scale (EQ VAS). The impact of obesity on HRQL was examined through multivariate regression, adjusting for sociodemographics and disease status. RESULTS: After adjustment, HRQL decreased with increasing level of obesity. Compared to normal weight respondents, persons with severe obesity had significantly lower scores with scores on the PCS-12, MCS-12, EQ-5D index, and EQ VAS being 4.0, 1.1, 0.073, and 4.8 points lower, respectively. Such decrements of HRQL for severe obesity were similar to the decrements seen for diabetes or hypertension. Persons with moderate obesity or who were overweight also had significantly lower HRQL scores, particularly on the PCS-12 and EQ-5D index. Underweight persons also had lower MCS-12 and EQ VAS scores. CONCLUSIONS: Persons with obesity had significantly lower HRQL than those who were normal weight and such lower scores were seen even for persons without chronic diseases known to be linked to obesity.

As is well known Walter Benjamin devoted his unfinished magnum opus to arcades, the covered shopping galleries that emerged in the mid 19th century, as the central image revealing the economic, socio-political, and cultural features of that era. From Benjamin’s point of view these were the direct material embodiment of self-consciousness, or rather, of an unconscious society fascinated by the capitalist spectacle unfolding before its eyes. Arcades reflect all the errors and shortcomings of bourgeois consciousness — commodity fetishism, reification, taking the world as a “thing in itself”, they reflect its utopian fantasies (fashion, prostitution, and gambling). In addition, they represented the first truly international style of modern architecture that became a commonplace for a whole generation of metropolitan residents the world over. By the end of the 19th century, arcades had become an integral element of any «modern» metropolis, and were imitated from Cleveland to Istanbul, from Glasgow to Johannesburg, from Buenos Aires to Melbourne. And, as Benjamin well knew, they could be found in each of the cities that had become vectors of his intellectual compass: Naples, Moscow, Paris and Berlin, setting points of intersection between vectors leading from west to east and from south to north. If the first vector indicates the movement of historical progress in terms of the realization of social and technological potential, the second evaluates history retrospectively, seeing in it mainly the ruins of an unrealized past.

OBJECTIVES: To determine what effect driving cessation may have on subsequent health and well-being in older adults. DESIGN: Systematic review of the evidence in the research literature on the consequences of driving cessation in older adults. SETTING: Community. PARTICIPANTS: Drivers aged 55 and older. MEASUREMENTS: Studies pertinent to the health consequences of driving cessation were identified through a comprehensive search of bibliographic databases. Studies that presented quantitative data for drivers aged 55 and older; used a cross-sectional, cohort, or case-control design; and had a comparison group of current drivers were included in the review. RESULTS: Sixteen studies met the inclusion criteria. Driving cessation was reported to be associated with declines in general health and physical, social, and cognitive function and with greater risks of admission to long-term care facilities and mortality. A meta-analysis based on pooled data from five studies examining the association between driving cessation and depression revealed that driving cessation almost doubled the risk of depressive symptoms in older adults (summary odds ratio = 1.91, 95% confidence interval = 1.61-2.27). CONCLUSION: Driving cessation in older adults appears to contribute to a variety of health problems, particularly depression. These adverse health consequences should be considered in making the decision to cease driving. Intervention programs ensuring mobility and social functions may be needed to mitigate the potential adverse effects of driving cessation on health and well-being in older adults.

Abstract It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses general linear models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g. counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2’s linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel disease (IBD) across multiple time points and omics profiles.

Endothelial cells (ECs) line all blood vessel walls and are exposed to the mechanical forces of blood flow which modulate their function and play a role in vascular regulation, remodelling and disease. The principal mechanical forces sensed by ECs are the shear stress of flowing blood on their apical surface, and the circumferential stress resisting blood pressure, which induces stretch in the cell body. 'Mechanotransduction' refers to the mechanisms by which these forces are transduced into biomolecular responses of the cells. Given the importance of endothelial mechanotransduction in cardiovascular physiology and pathology, numerous research efforts have been dedicated to identifying the mechanosensory component(s) of ECs. This review focuses on mechanotransduction of shear stress by ECs and considers the evidence in support of the surface glycocalyx acting as a mechanotransducer.

Transdisciplinarity originated in a critique of the standard configuration of knowledge in disciplines in the curriculum, including moral and ethical concerns. Pronouncements about it were first voiced between the climax of government-supported science and higher education and the long retrenchment that began in the 1970s. Early work focused on questions of epistemology and the planning of future universities and educational programs. After a lull, transdisciplinarity re-emerged in the 1990s as an urgent issue relating to the solution of new, highly complex, global concerns, beginning with climate change and sustainability and extending into many areas concerning science, technology, social problems and policy, education, and the arts. Transdisciplinarity today is characterized by its focus on “wicked problems” that need creative solutions, its reliance on stakeholder involvement, and engaged, socially responsible science. In simultaneously studying multiple levels of, and angles on, reality, transdisciplinary work provides an intriguing potential to invigorate scholarly and scientific inquiry both in and outside the academy.

Scholars and practitioners alike in recent years have suggested that real and lasting progress in the fight against gun violence requires changing the social norms and attitudes that perpetuate violence and the use of guns. The Cure Violence model is a public health approach to gun violence reduction that seeks to change individual and community attitudes and norms about gun violence. It considers gun violence to be analogous to a communicable disease that passes from person to person when left untreated. Cure Violence operates independently of, while hopefully not undermining, law enforcement. In this article, we describe the theoretical basis for the program, review existing program evaluations, identify several challenges facing evaluators, and offer directions for future research.

Justice and Nature THOMAS NAGEL THOMAS NAGEL **School of Law, New York UniversityNY, USA Search for other works by this author on: Oxford Academic Google Scholar Oxford Journal of Legal Studies, Volume 17, Issue 2, Summer 1997, Pages 303–321, https://doi.org/10.1093/ojls/17.2.303 Published: 01 July 1997

Ecosystem recovery from anthropogenic disturbances, either without human intervention or assisted by ecological restoration, is increasingly occurring worldwide. As ecosystems progress through recovery, it is important to estimate any resulting deficit in biodiversity and functions. Here we use data from 3,035 sampling plots worldwide, to quantify the interim reduction of biodiversity and functions occurring during the recovery process (that is, the 'recovery debt'). Compared with reference levels, recovering ecosystems run annual deficits of 46-51% for organism abundance, 27-33% for species diversity, 32-42% for carbon cycling and 31-41% for nitrogen cycling. Our results are consistent across biomes but not across degrading factors. Our results suggest that recovering and restored ecosystems have less abundance, diversity and cycling of carbon and nitrogen than 'undisturbed' ecosystems, and that even if complete recovery is reached, an interim recovery debt will accumulate. Under such circumstances, increasing the quantity of less-functional ecosystems through ecological restoration and offsetting are inadequate alternatives to ecosystem protection.

Upgraded electronics, improved water system dynamics, better calibration and analysis techniques allowed Super-Kamiokande-IV to clearly observe very low-energy 8 B solar neutrino interactions, with recoil electron kinetic energies as low as 3.5 MeV. Super-Kamiokande-IV data-taking began in September of 2008; this paper includes data until February 2014, a total livetime of 1664 days. The measured solar neutrino flux is (2.308 0.020(stat.) +0.039 -0.040 (syst.)) 10 6 /(cm 2 sec) assuming no oscillations. The observed recoil electron energy spectrum is consistent with no distortions due to neutrino oscillations. An extended maximum likelihood fit to the amplitude of the expected solar zenith angle variation of the neutrino-electron elastic scattering rate in SK-IV results in a day/night asymmetry of (-3.6 1.6(stat.) 0.6(syst.))%. The SK-IV solar neutrino data determine the solar mixing angle as sin 2 12 = 0.327 +0.026 -0.031 , all SK solar data (SK-I, SK-II, SK III and SK-IV) measures this angle to be sin 2 12 = 0.334 +0.027 -0.023 , the determined mass-squared splitting is m 2 21 = 4.8 +1.5 -0.8 10 -5 eV 2 .

A pooled post-hoc analysis of the phase 3, randomized, placebo-controlled BLISS trials (1684 patients with active systemic lupus erythematosus (SLE)) was performed to evaluate the effect of belimumab on renal parameters in patients with renal involvement at baseline, and to explore whether belimumab offered additional renal benefit to patients receiving mycophenolate mofetil at baseline. In addition to belimumab or placebo, all patients received standard SLE therapy. Patients with severe active lupus nephritis were excluded from the trials. Over 52 weeks, rates of renal flare, renal remission, renal organ disease improvement (assessed by Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group), proteinuria reduction, grade 3/4 proteinuria, and serologic activity favored belimumab, although the between-group differences in most renal outcomes were not significant. Among the 267 patients with renal involvement at baseline, those receiving mycophenolate mofetil or with serologic activity at baseline had greater renal organ disease improvement with belimumab than with placebo. Limitations of this analysis included the small patient numbers and the post-hoc nature of this pooled analysis. The results suggest that belimumab may offer renal benefit in patients with SLE. Further study is warranted in patients with severe active lupus nephritis.

Amazonian environments are being degraded by modern industrial and agricultural activities at a pace far above anything previously known, imperiling its vast biodiversity reserves and globally important ecosystem services. The most substantial threats come from regional deforestation, because of export market demands, and global climate change. The Amazon is currently perched to transition rapidly from a largely forested to a nonforested landscape. These changes are happening much too rapidly for Amazonian species, peoples, and ecosystems to respond adaptively. Policies to prevent the worst outcomes are known and must be enacted immediately. We now need political will and leadership to act on this information. To fail the Amazon is to fail the biosphere, and we fail to act at our peril.

We assessed the appropriate geographic scale to apply an area deprivation index (ADI), which reflects a geographic area's level of socioeconomic deprivation and is associated with health outcomes, to identify and screen patients for social determinants of health. We estimated the relative strength of the association between the ADI at various geographic levels and a range of hospitalization rates by using age-adjusted odds ratios in an 8-county region of New York State. The 10-km local ADI estimates had the strongest associations with all hospitalization rates (higher odds ratios) followed by estimates at 20 km, 30 km, and the regional scale. A locally sensitive ADI is an ideal measure to identify and screen for the health care and social services needs and to advance the integration of social determinants of health with clinical treatment and disease prevention.

Intramanchette transport (IMT) and intraflagellar transport (IFT) share similar molecular components: a raft protein complex transporting cargo proteins mobilized along microtubules by molecular motors. IFT, initially discovered in flagella of Chlamydomonas, has been also observed in cilia of the worm Caenorhabditis elegans and in mouse ciliated and flagellated cells. IFT has been defined as the mechanism by which protein raft components (also called IFT particles) are displaced between the flagellum and the plasma membrane in the anterograde direction by kinesin-II and in the retrograde direction by cytoplasmic dynein 1b. Mutation of the gene Tg737, encoding one of the components of the raft protein complex, designated Polaris in the mouse and IFT88 in both Chlamydomonas and mouse, results in defective ciliogenesis and flagellar development as well as asymmetry in left-right axis determination. Polaris/IFT88 is detected in the manchette of mouse and rat spermatids. Indications of an IMT mechanism originated from the finding that two proteins associated with the manchette (Sak57/K5 and TBP-1, the latter a component of the 26S proteasome) repositioned to the centrosome and sperm tail once the manchette disassembled. IMT has the features of the IFT machinery but, in addition, facilitates nucleocytoplasmic exchange activities during spermiogenesis. An example is Ran, a small GTPase present in the nucleus and cytoplasm of round spermatids and in the manchette of elongating spermatids. Upon disassembly of the manchette, Ran GTPase is found in the centrosome region of elongating spermatids. Because defective molecular motors and raft proteins result in defective flagella, cilia, and cilia-containing photoreceptor cells in the retina, IMT and IFT are emerging as essential mechanisms for managing critical aspects of sperm development. Details of specific role of Ran GTPase in nucleocytoplasmic transport and its relocation from the manchette to the centrosome to the sperm tail await elucidation.

BACKGROUND/OBJECTIVE: The understanding and practice of public health crisis communication are improved through the study of responses to past crises, but require retooling for present challenges. The 'Addressing Ebola and other outbreaks' checklist contains guiding principles built upon maxims developed from a World Health Organization consultation in response to the mad cow (bovine spongiform encephalopathy) crisis that were later adopted for Ebola. The purpose of this article is to adapt the checklist for the health communication challenges and public health practices that have emerged during the coronavirus disease 2019 (COVID-19) pandemic. The communication challenges of promoting vaccine acceptance are used to illustrate a key area that requires strengthened communication. Type of program or service: Effective communication principles for application during the COVID-19 pandemic. RESULTS: The COVID-19 pandemic has introduced unique challenges for public health practitioners and health communicators that warrant an expansion of existing health communication principles to take into consideration: the new infodemic (or mis/disinfodemic) challenge - particularly as treatments and vaccines are being developed; communication of risk and uncertainty; health-information behaviours and the instantaneous nature of social media, and the relationship between media literacy and health literacy; the effects of the pandemic on other health issues; and the need for a flexible communication strategy that adapts to the different stages of the pandemic. LESSONS LEARNT: Principles discussed in this article will help build preparedness capacity and offer communication strategies for moving from the acute phase to the 'next normal' with likely prevention (e.g. herd immunity achieved through vaccination) and societal COVID-19 resilience.

The granular convoluted tubule (GCT) is a segment of the duct system of all rodents, situated between the striated and intercalated ducts. It has the peculiar property of synthesizing a large variety of biologically active polypeptides whose role in saliva remains unknown. The literature on the fine structure of GCT cells is critically reviewed. Some recent developments on endocrine regulation of the structure and contents of rodent GCT cells are summarized, with emphasis on EGF, NGF, renin, and kallikrein proteases. A survey of the distribution of GCT cells in several vertebrate families is presented.

PURPOSE: Infection with COVID-19 potentially can result in severe outcomes and death from "cytokine storm syndrome", resulting in novel coronavirus pneumonia (NCP) with severe dyspnea, acute respiratory distress syndrome (ARDS), fulminant myocarditis and multiorgan dysfunction with or without disseminated intravascular coagulation. No published treatment to date has been shown to adequately control the inflammation and respiratory symptoms associated with COVID-19, apart from oxygen therapy and assisted ventilation. We evaluated the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients with dyspnea secondary to COVID-19 pneumonia. METHODS: Two patients living in New York City (NYC) with a history of Lyme and tick-borne co-infections experienced a cough and dyspnea and demonstrated radiological findings consistent with novel coronavirus pneumonia (NCP). A trial of 2 g of PO or IV glutathione was used in both patients and improved their dyspnea within 1 h of use. Repeated use of both 2000 mg of PO and IV glutathione was effective in further relieving respiratory symptoms. CONCLUSION: Oral and IV glutathione, glutathione precursors (N-acetyl-cysteine) and alpha lipoic acid may represent a novel treatment approach for blocking NF-κB and addressing "cytokine storm syndrome" and respiratory distress in patients with COVID-19 pneumonia.