New York Proton Center

The performance of prediction models can be assessed using a variety of methods and metrics. Traditional measures for binary and survival outcomes include the Brier score to indicate overall model performance, the concordance (or c) statistic for discriminative ability (or area under the receiver operating characteristic [ROC] curve), and goodness-of-fit statistics for calibration.Several new measures have recently been proposed that can be seen as refinements of discrimination measures, including variants of the c statistic for survival, reclassification tables, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Moreover, decision-analytic measures have been proposed, including decision curves to plot the net benefit achieved by making decisions based on model predictions.We aimed to define the role of these relatively novel approaches in the evaluation of the performance of prediction models. For illustration, we present a case study of predicting the presence of residual tumor versus benign tissue in patients with testicular cancer (n = 544 for model development, n = 273 for external validation).We suggest that reporting discrimination and calibration will always be important for a prediction model. Decision-analytic measures should be reported if the predictive model is to be used for clinical decisions. Other measures of performance may be warranted in specific applications, such as reclassification metrics to gain insight into the value of adding a novel predictor to an established model.

In Brief Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage −3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage −1) and early postmenopause (Stage +1), and recommended application regardless of women’s age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive and the early postmenopause stages, provided information on the duration of the late transition and early postmenopause, and recommended application regardless of women’s age, ethnicity, body size, or lifestyle characteristics.

PURPOSE: To establish the safety, pharmacokinetics, and recommended dose of sunitinib, a novel oral multitargeting tyrosine kinase inhibitor with antiangiogenic and antitumor properties, in patients with advanced malignancies. PATIENTS AND METHODS: Sunitinib was given orally for 4 weeks every 6 weeks. RESULTS: Twenty-eight patients received doses ranging from 15 to 59 mg/m2 (ranging from 50 mg every other day to 150 mg/d). Dose-limiting toxicities reported at the maximum-tolerated doses > or = 75 mg/d were reversible grade 3 fatigue, grade 3 hypertension, and grade 2 bullous skin toxicity. Therefore, the recommended dose was 50 mg/d. At this dose, the main adverse effects were sore mouth, edema, and thrombocytopenia. Hair discoloration and yellow coloration of the skin were observed at doses > or = 50 mg/d. Pharmacokinetic data indicate that potentially active target plasma concentrations > or = 50 ng/mL can be achieved with moderate interpatient variability and a long half-life compatible with a single daily dosing. Six objective responses were observed in three renal cell carcinomas, one neuroendocrine tumor, one stromal tumor, and one unknown primary adenocarcinoma patient. At higher doses (> or = 75 mg/d), tumor responses were often associated with reduced intratumoral vascularization and central tumor necrosis, eventually resulting in organ perforation or fistula. CONCLUSION: At the dose of 50 mg/d (4 weeks on, 2 weeks off), sunitinib displays manageable toxicity. Antitumor activity supports further studies in patients with renal cell carcinoma, gastrointestinal, neuroendocrine, and stromal tumors. Future studies may consider including prospective imaging techniques such as high frequency ultrasound to monitor tumor density.

To estimate the current incidence and prevalence in the United States of 12 neurologic disorders.We summarize the strongest evidence available, using data from the United States or from other developed countries when US data were insufficient.For some disorders, prevalence is a better descriptor of impact; for others, incidence is preferable. Per 1,000 children, estimated prevalence was 5.8 for autism spectrum disorder and 2.4 for cerebral palsy; for Tourette syndrome, the data were insufficient. In the general population, per 1,000, the 1-year prevalence for migraine was 121, 7.1 for epilepsy, and 0.9 for multiple sclerosis. Among the elderly, the prevalence of Alzheimer disease was 67 and that of Parkinson disease was 9.5. For diseases best described by annual incidence per 100,000, the rate for stroke was 183, 101 for major traumatic brain injury, 4.5 for spinal cord injury, and 1.6 for ALS.Using the best available data, our survey of a limited number of disorders shows that the burden of neurologic illness affects many millions of people in the United States.

The human brain has evolved for group living [1Dunbar I.R. The social brain hypothesis.in: Cacioppo J.T. Foundations in Social Neuroscience. MIT Press, 2002: 69-88Google Scholar]. Yet we know so little about how it supports dynamic group interactions that the study of real-world social exchanges has been dubbed the “dark matter of social neuroscience” [2Schilbach L. Timmermans B. Reddy V. Costall A. Bente G. Schlicht T. Vogeley K. Toward a second-person neuroscience.Behav. Brain Sci. 2013; 36: 393-414Crossref PubMed Scopus (890) Google Scholar]. Recently, various studies have begun to approach this question by comparing brain responses of multiple individuals during a variety of (semi-naturalistic) tasks [3Babiloni F. Astolfi L. Social neuroscience and hyperscanning techniques: past, present and future.Neurosci. Biobehav. Rev. 2014; 44: 76-93Crossref PubMed Scopus (289) Google Scholar, 4Dmochowski J.P. Bezdek M.A. Abelson B.P. Johnson J.S. Schumacher E.H. Parra L.C. Audience preferences are predicted by temporal reliability of neural processing.Nat. Commun. 2014; 5: 4567Crossref PubMed Scopus (164) Google Scholar, 5Dumas G. Nadel J. Soussignan R. Martinerie J. Garnero L. Inter-brain synchronization during social interaction.PLoS ONE. 2010; 5: e12166Crossref PubMed Scopus (495) Google Scholar, 6Hasson U. Ghazanfar A.A. Galantucci B. Garrod S. Keysers C. Brain-to-brain coupling: a mechanism for creating and sharing a social world.Trends Cogn. Sci. 2012; 16: 114-121Abstract Full Text Full Text PDF PubMed Scopus (545) Google Scholar, 7Hari R. Himberg T. Nummenmaa L. Hämäläinen M. Parkkonen L. Synchrony of brains and bodies during implicit interpersonal interaction.Trends Cogn. Sci. 2013; 17: 105-106Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Jiang J. Chen C. Dai B. Shi G. Ding G. Liu L. Lu C. Leader emergence through interpersonal neural synchronization.Proc. Natl. Acad. Sci. USA. 2015; 112: 4274-4279Crossref PubMed Scopus (168) Google Scholar, 9Pfeiffer U.J. Timmermans B. Vogeley K. Frith C.D. Schilbach L. Towards a neuroscience of social interaction.Front. Hum. Neurosci. 2013; 7: 22Crossref PubMed Scopus (30) Google Scholar, 10Stephens G.J. Silbert L.J. Hasson U. Speaker-listener neural coupling underlies successful communication.Proc. Natl. Acad. Sci. USA. 2010; 107: 14425-14430Crossref PubMed Scopus (546) Google Scholar, 11Babiloni C. Buffo P. Vecchio F. Marzano N. Del Percio C. Spada D. Rossi S. Bruni I. Rossini P.M. Perani D. Brains “in concert”: frontal oscillatory alpha rhythms and empathy in professional musicians.Neuroimage. 2012; 60: 105-116Crossref PubMed Scopus (84) Google Scholar, 12Duan L. Dai R.N. Xiao X. Sun P.P. Li Z. Zhu C.Z. Cluster imaging of multi-brain networks (CIMBN): a general framework for hyperscanning and modeling a group of interacting brains.Front. Neurosci. 2015; 9: 267Crossref PubMed Scopus (28) Google Scholar, 13Hasson U. Nir Y. Levy I. Fuhrmann G. Malach R. Intersubject synchronization of cortical activity during natural vision.Science. 2004; 303: 1634-1640Crossref PubMed Scopus (1063) Google Scholar, 14Nummenmaa L. Glerean E. Viinikainen M. Jääskeläinen I.P. Hari R. Sams M. Emotions promote social interaction by synchronizing brain activity across individuals.Proc. Natl. Acad. Sci. USA. 2012; 109: 9599-9604Crossref PubMed Scopus (287) Google Scholar, 15Dikker S. Silbert L.J. Hasson U. Zevin J.D. On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.J. Neurosci. 2014; 34: 6267-6272Crossref PubMed Scopus (71) Google Scholar]. These experiments reveal how stimulus properties [13Hasson U. Nir Y. Levy I. Fuhrmann G. Malach R. Intersubject synchronization of cortical activity during natural vision.Science. 2004; 303: 1634-1640Crossref PubMed Scopus (1063) Google Scholar], individual differences [14Nummenmaa L. Glerean E. Viinikainen M. Jääskeläinen I.P. Hari R. Sams M. Emotions promote social interaction by synchronizing brain activity across individuals.Proc. Natl. Acad. Sci. USA. 2012; 109: 9599-9604Crossref PubMed Scopus (287) Google Scholar], and contextual factors [15Dikker S. Silbert L.J. Hasson U. Zevin J.D. On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.J. Neurosci. 2014; 34: 6267-6272Crossref PubMed Scopus (71) Google Scholar] may underpin similarities and differences in neural activity across people. However, most studies to date suffer from various limitations: they often lack direct face-to-face interaction between participants, are typically limited to dyads, do not investigate social dynamics across time, and, crucially, they rarely study social behavior under naturalistic circumstances. Here we extend such experimentation drastically, beyond dyads and beyond laboratory walls, to identify neural markers of group engagement during dynamic real-world group interactions. We used portable electroencephalogram (EEG) to simultaneously record brain activity from a class of 12 high school students over the course of a semester (11 classes) during regular classroom activities (Figures 1A–1C; Supplemental Experimental Procedures, section S1). A novel analysis technique to assess group-based neural coherence demonstrates that the extent to which brain activity is synchronized across students predicts both student class engagement and social dynamics. This suggests that brain-to-brain synchrony is a possible neural marker for dynamic social interactions, likely driven by shared attention mechanisms. This study validates a promising new method to investigate the neuroscience of group interactions in ecologically natural settings.

The incorporation of silica nanoparticles into polyethylene increased the breakdown strength and voltage endurance significantly compared to the incorporation of micron scale fillers. In addition, dielectric spectroscopy showed a decrease in dielectric permittivity for the nanocomposite over the base polymer, and changes in the space charge distribution and dynamics have been documented. The most significant difference between micron scale and nanoscale fillers is the tremendous increase in interfacial area in nanocomposites. Because the interfacial region (interaction zone) is likely to be pivotal in controlling properties, the bonding between the silica and polyethylene was characterized using Fourier transformed infrared (FTTR) spectroscopy, electron paramagnetic resonance (EPR), and x-ray photoelectron spectroscopy (XPS). The picture which is emerging suggests that the enhanced interfacial zone, in addition to particle-polymer bonding, plays a very important role in determining the dielectric behavior of nanocomposites.

Anti-infectives, including antibiotics, are essentially different from all other drugs; they not only affect the individual to whom they are given but also the entire community, through selection for resistance to their own action. Thus, their use resides at the intersection of personal and public health. Antibiotics can be likened to a four-edged sword against bacteria. The first two edges of the antibiotic sword were identified immediately after their discovery and deployment in that they not only benefit an individual in treating their infection but also benefit the community in preventing the spread of that infectious agent. The third edge was already recognized by Alexander Fleming in 1945 in his Nobel acceptance speech, which warned about the cost to the community of antibiotic resistance that would inevitably evolve and be selected for during clinical practice. We have seen this cost mount up, as resistance curtails or precludes the activities of some of our most effective drugs for clinically important infections. But the fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.

and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

The subject here is generalized (i.e., non-Gaussian) noise models, and specifically their first-order probability density functions (PDFs). Attention is focused primarily on the author's canonical statistical-physical Class A and Class B models. In particular, Class A noise describes the type of electromagnetic interference (EMI) often encountered in telecommunication applications, where this ambient noise is largely due to other, "intelligent" telecommunication operations. On the other hand, ambient Class B noise usually represents man-made or natural "nonintelligent"-i.e., nonmessage-bearing noise-and is highly impulsive. Class A noise is not an /spl alpha/-stable process, nor is it reducible to such, except in the limiting Gaussian cases of high-density noise (by the central limit theorem). Class B noise is also asymptotically normal (before model approximation). Under rather broad conditions, principally governed by the source propagation and distribution scenarios, the PDF of Class B noise alone (no Gaussian component) can usually be approximated by (1) a symmetric Gaussian /spl alpha/-stable (S/spl alpha/S) model in the case of narrowband reception, or when the PDF /spl omega//sub 1/(/spl alpha/) of the amplitude is symmetric; and (2) a nonsymmetric /spl alpha/-stable (NS/spl alpha/S) model (no Gaussian component) can be constructed in broadband regimes. New results here include: (i) counting functional methods for constructing the general qth-order characteristic functions (CFs) of Class A and Class B noise, from which (all) moments and (in principle), the PDFs follow; (ii) the first-order CFs, PDFs, and cumulative probabilities (APDs) of nonsymmetric broadband Class B noise, extended to include additive Gauss noise (AGN); (iii) proof of the existence of all moments in the basic Class A and Class B models; (iv) the key physical role of AGN and the fact that AGN removes /spl alpha/-stability; (v) the explicit roles of the propagation and distribution scenarios; and (vi) extension to noise fields. Although telecommunication applications are emphasized, Class A and Class B noise models apply selectively, but equally well, to other physical regimes, e.g., underwater acoustics and EM (radar, optics, etc.). Supportive empirical data are included.

INTRODUCTION: Accurate estimates of prevalence/incidence are important in understanding the true burden of male and female sexual dysfunction and in identifying risk factors for prevention efforts. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the epidemiology/risk factors of sexual dysfunctions in men and women. METHODS: An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a 2-year period. Concerning the Epidemiology/Risk Factors Committee, there were seven experts from four countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Standard definitions of male and female sexual dysfunctions are needed. The incidence rate for erectile dysfunction is 25-30 cases per thousand person years and increases with age. There are no parallel data for women's sexual dysfunctions. The prevalence of sexual dysfunction increases as men and women age; about 40-45% of adult women and 20-30% of adult men have at least one manifest sexual dysfunction. Common risk factor categories associated with sexual dysfunction exist for men and women including: individual general health status, diabetes mellitus, cardiovascular disease, other genitourinary disease, psychiatric/psychological disorders, other chronic diseases, and socio-demographic conditions. Endothelial dysfunction is a condition present in many cases of erectile dysfunction and there are common etiological pathways for other vascular disease states. Increasing physical activity lowers incidence of ED in males who initiate follow-up in their middle ages. CONCLUSIONS: There is a need for more epidemiologic research in male and female sexual dysfunction.

We report on the synthesis of a phase-pure, 2-dimensional transition metal carbide Nb4C3, produced by immersing Nb4AlC3 powders in hydrofluoric acid. The structure of this, only second MXene with formula M4X3, was investigated with pair distribution function analysis. The resistivity of a cold-pressed disc was 0.0046 Ω m, rendering this MXene one of the most conductive to date.

Established tumors are typified by an immunosuppresive microenvironment. Countering this naturally occurring phenomenon, emerging evidence suggests that radiation promotes a proimmunogenic milieu within the tumor capable of stimulating host cancer-specific immune responses. Three cryptic immunogenic components of cytotoxic-agent induced cell death-namely, calreticulin cell surface exposure, the release of high mobility group box 1 (HMGB1) protein, and the liberation of ATP-have been previously shown to be critical for dendritic cell (DC) activation and effector T-cell priming. Thus, these immune-mobilizing components commonly presage tumor rejection in response to treatment. We initially set out to address the hypothesis that radiation-induced immunogenic cell death (ICD) is dose-dependent. Next, we hypothesized that radiation would enhance chemotherapy-induced ICD when given concomitantly, as suggested by the favorable clinical outcomes observed in response to analogous concurrent chemoradiation regimens. Thus, we designed an in vitro assay to examine the 3 hallmark features of ICD at clinically relevant doses of radiation. We then tested the immunogenic-death inducing effects of radiation combined with carboplatin or paclitaxel, focusing on these combinations to mimic chemoradiation regimens actually used in clinical trials of early stage triple negative [NCT0128953/NYU-10-01969] and locally advanced [NYU-06209] breast cancer patients, respectively. Despite the obvious limitations of an in vitro model, radiotherapy produced both a dose-dependent induction and chemotherapeutic enhancement of ICD. These findings provide preliminary evidence that ICD stimulated by either high-dose radiotherapy alone, or concurrent chemoradiation regimens, may contribute to the establishment of a peritumoral proimmunogenic milieu.

Importance: To our knowledge, there have been no clinical trials of ultra-high-dose-rate radiotherapy delivered at more than 40 Gy/sec, known as FLASH therapy, nor first-in-human use of proton FLASH. Objectives: To assess the clinical workflow feasibility and treatment-related toxic effects of FLASH and pain relief at the treatment sites. Design, Setting, and Participants: In the FAST-01 nonrandomized trial, participants treated at Cincinnati Children's/UC Health Proton Therapy Center underwent palliative FLASH radiotherapy to extremity bone metastases. Patients 18 years and older with 1 to 3 painful extremity bone metastases and life expectancies of 2 months or more were eligible. Patients were excluded if they had foot, hand, and wrist metastases; metastases locally treated in the 2 weeks prior; metal implants in the treatment field; known enhanced tissue radiosensitivity; and implanted devices at risk of malfunction with radiotherapy. One of 11 patients who consented was excluded based on eligibility. The end points were evaluated at 3 months posttreatment, and patients were followed up through death or loss to follow-up for toxic effects and pain assessments. Of the 10 included patients, 2 died after the 2-month follow-up but before the 3-month follow-up; 8 participants completed the 3-month evaluation. Data were collected from November 3, 2020, to January 28, 2022, and analyzed from January 28, 2022, to September 1, 2022. Interventions: Bone metastases were treated on a FLASH-enabled (≥40 Gy/sec) proton radiotherapy system using a single-transmission proton beam. This is consistent with standard of care using the same prescription (8 Gy in a single fraction) but on a conventional-dose-rate (approximately 0.03 Gy/sec) photon radiotherapy system. Main Outcome and Measures: Main outcomes included patient time on the treatment couch, device-related treatment delays, adverse events related to FLASH, patient-reported pain scores, and analgesic use. Results: A total of 10 patients (age range, 27-81 years [median age, 63 years]; 5 [50%] male) underwent FLASH radiotherapy at 12 metastatic sites. There were no FLASH-related technical issues or delays. The average (range) time on the treatment couch was 18.9 (11-33) minutes per patient and 15.8 (11-22) minutes per treatment site. Median (range) follow-up was 4.8 (2.3-13.0) months. Adverse events were mild and consistent with conventional radiotherapy. Transient pain flares occurred in 4 of the 12 treated sites (33%). In 8 of the 12 sites (67%) patients reported pain relief, and in 6 of the 12 sites (50%) patients reported a complete response (no pain). Conclusions and Relevance: In this nonrandomized trial, clinical workflow metrics, treatment efficacy, and safety data demonstrated that ultra-high-dose-rate proton FLASH radiotherapy was clinically feasible. The treatment efficacy and the profile of adverse events were comparable with those of standard-of-care radiotherapy. These findings support the further exploration of FLASH radiotherapy in patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT04592887.

CONTEXT: Universal screening for mental health problems and suicide risk is at the forefront of the national agenda for youth suicide prevention, yet no study has directly addressed the potential harm of suicide screening. OBJECTIVE: To examine whether asking about suicidal ideation or behavior during a screening program creates distress or increases suicidal ideation among high school students generally or among high-risk students reporting depressive symptoms, substance use problems, or suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled study conducted within the context of a 2-day screening strategy. Participants were 2342 students in 6 high schools in New York State in 2002-2004. Classes were randomized to an experimental group (n = 1172), which received the first survey with suicide questions, or to a control group (n = 1170), which did not receive suicide questions. MAIN OUTCOME MEASURES: Distress measured at the end of the first survey and at the beginning of the second survey 2 days after the first measured on the Profile of Mood States adolescent version (POMS-A) instrument. Suicidal ideation assessed in the second survey. RESULTS: Experimental and control groups did not differ on distress levels immediately after the first survey (mean [SD] POMS-A score, 5.5 [9.7] in the experimental group and 5.1 [10.0] in the control group; P = .66) or 2 days later (mean [SD] POMS-A score, 4.3 [9.0] in the experimental group and 3.9 [9.4] in the control group; P = .41), nor did rates of depressive feelings differ (13.3% and 11.0%, respectively; P = .19). Students exposed to suicide questions were no more likely to report suicidal ideation after the survey than unexposed students (4.7% and 3.9%, respectively; P = .49). High-risk students (defined as those with depression symptoms, substance use problems, or any previous suicide attempt) in the experimental group were neither more suicidal nor distressed than high-risk youth in the control group; on the contrary, depressed students and previous suicide attempters in the experimental group appeared less distressed (P = .01) and suicidal (P = .02), respectively, than high-risk control students. CONCLUSIONS: No evidence of iatrogenic effects of suicide screening emerged. Screening in high schools is a safe component of youth suicide prevention efforts.

BACKGROUND: Diagnosis and reduction of syndesmosis injuries in ankle fractures can be challenging. Previous studies have demonstrated that standard radiographic measurements used to evaluate the integrity of the syndesmosis are inaccurate. The purpose of this study was to determine the adequacy of standard postoperative radiographic measurements in assessing syndesmotic reduction compared to CT and to determine the prevalence of postoperative syndesmotic malreduction in a patient cohort. METHODS: Twenty-five patients with ankle fractures and syndesmotic instability who had open reduction and syndesmotic fixation were evaluated. All patients had a standard radiographic series postoperatively followed by a CT scan. Radiographic measurements were made by three observers to determine the tibiofibular relationship. Axial CT scan images were judged for quality of reduction of the syndesmosis by measuring the distance between the fibula and the anterior and posterior facets of the incisura. Differences between the anterior and posterior measurements of more than 2 mm were considered incongruous. RESULTS: Six patients (24%) had evidence of postoperative diastasis using the radiographic criteria, four of whom had evidence of malreduction on postoperative CT scan. Conversely, 13 patients (52%) had incongruity of the fibula within the incisura on CT scan (average 3.6 mm, range 2.0 to 8.0 mm), only four of whom had one or more abnormal radiographic measurements. In 10 (77%) of the 13 malreductions seen on CT scan, the posterior measurement was greater, indicating that internal rotation or anterior translation of the fibula may have occurred. Sensitivity of radiographs was 31% and the specificity was 83% compared to CT. CONCLUSIONS: Many syndesmoses were malreduced on CT scan but went undetected by plain radiographs. Radiographic measurements did not accurately reflect the status of the distal tibiofibular joint in this series of ankle fractures. Furthermore, postreduction radiographic measurements were inaccurate for assessing the quality of the reduction. Although we did not seek to correlate functional outcomes, the known morbidity of postoperative syndesmotic malreduction should lead to heightened vigilance for assessing accurate syndesmosis reduction intraoperatively.

Acid-aspiration pneumonitis is a significant cause of anesthetic maternal mortality. A study of 100 patients for cesarean section (c-section) showed that the presence of a high gastric content volume or a low pH cannot be excluded in any patient, irrespective of the time between the last meal and either onset of labor or delivery. Patients for elective c-section are equally, if not more, at risk. Administration of oral antacid within 4 hours of inducing anesthesia did not affect the gastric content volume but significantly raised the pH. The number of patients at risk of developing acid-aspiration pneumonitis was reduced tenfold. The authors conclude that every parturient should receive oral antacid before induction of general anesthesia.

The Atg1/ULK1 complex plays a central role in starvation-induced autophagy, integrating signals from upstream sensors such as MTOR and AMPK and transducing them to the downstream autophagy pathway. Much progress has been made in the last few years in understanding the mechanisms by which the complex is regulated through protein-protein interactions and post-translational modifications, providing insights into how the cell modulates autophagy, particularly in response to nutrient status. However, how the ULK1 complex transduces upstream signals to the downstream central autophagy pathway is still unclear. Although the protein kinase activity of ULK1 is required for its autophagic function, its protein substrate(s) responsible for autophagy activation has not been identified. Furthermore, examples of potential ULK1-independent autophagy have emerged, indicating that under certain specific contexts, the ULK1 complex might be dispensable for autophagy activation. This raises the question of how the autophagic machinery is activated independent of the ULK1 complex and what are the biological functions of such noncanonical autophagy pathways.

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

The authors calculated the progression rate (ΔFS) using the total revised ALS Functional Rating Scale (ALSFRS-R) and symptom duration at diagnosis in 82 Japanese patients with ALS. Survival (death or tracheostomy) differed significantly with the ΔFS and postdiagnostic period according to log-rank testing, but Cox proportional hazards modeling revealed no strong association between total ALSFRS-R and mortality, suggesting that the ΔFS provides an additional predictive index beyond ALSFRS-R alone.