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Purpose To describe methods that can be used to quantify and compare harm caused by surgical interventions in ophthalmology trials. Design Perspective study Methods A published landmark glaucoma trial was used as an exemplar. A consensus-derived classification system of severity of complications was applied to published data of the Tube versus Trabeculectomy (TVT) glaucoma trial. The severity grade of each complication was multiplied to the number of patients who incurred that complication to estimate a total harm score for each intervention. Graphical tools were also used to display the differences in complications between trial arms. A review of literature on best practice for reporting ham data was also conducted. Results Analyzing treatment harm is challenging with the relatively small number of events and sample sizes used in randomized controlled trials. However quantification and graphical representation of harm after surgery is possible. Reframing the research question to one for detecting signals of adverse reactions and use of Bayesian analyses can be useful. Conclusions Analysis of harm data in clinical trials needs further attention. A severity classification system and a total harm score can be used to quantify harm after glaucoma surgery. Graphical tools can also help interpret complications data.

The current study examined the impact of the COVID-19 pandemic on perceived everyday discrimination and internalized racism among Asians compared to Latinxs. Recently, researchers have attempted to tackle institutional and interpersonal racism during this pandemic outbreak, however, few studies have addressed the internalized component of the racism. We launched this survey study during the critical months of the national pandemic lockdown (April 2020 to April 2021) with a sample (N = 360) of 170 Asians and 190 Latinxs college students self-reporting their experiences related to everyday discrimination and internalized racism. Findings indicated that Asians experienced more internalized racism and perceived a change in everyday discrimination during the COVID-19 pandemic compared to Latinxs. Furthermore, the perceived everyday discrimination during the COVID-19 pandemic emerged as a mediator for the race effect on internalized racism. That is, Asians perceived a significant change in everyday discrimination frequency during the COVID-19 pandemic compared to Latinxs and this change was related to higher levels of internalized racism. According to our findings, Asians perceived more daily discriminatory and inferiorizing messages, compared to Latinxs, which also explained the reasons for higher levels of internalized racism during the COVID-19 pandemic. Our findings suggest that Asians might be rationalizing their encounters with discrimination and even believing their communities deserve these daily attacks during the COVID-19 pandemic outbreak.

In the last two decades, urban insurgencies have become a major concern for scholars and practitioners. It is widely assumed that because half the human population now live in cities in often appalling conditions, it is inevitable that conflict has migrated to cities, not least because urban areas offer would-be insurgents the best opportunity to evade state security forces and their advanced technologies. Demography and asymmetry have been all but universally accepted in the literature as the sole causes of urban insurgency. They are certainly important. Yet, scholars have overlooked a third vital factor: the size of state forces. In the twentieth century, urban insurgencies were common. However, because states commanded very large military forces at that time, insurgents found it very difficult to operate in urban areas. By contrast, as their forces have contracted in the twenty-first century, states have been unable to dominate urban areas, as they typically did in the twentieth century. Consequently, urban enclaves have appeared inside cities from which insurgents have mounted their attacks and contested with state forces.

Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. Aim 1: Perform an interventional response phenotyping study in a cohort of cLBP patients (n = 400), who will receive a sequence of interventions known to be effective in cLBP. For 4 weeks, all cLBP participants will receive a web-based pain self-management program as part of a run-in period, then individuals who report no or minimal improvement will be randomized to: a) mindfulness-based stress reduction, b) physical therapy and exercise, c) acupressure self-management, and d) duloxetine. After 8 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 8 weeks. Using those data, we will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone.

When Israeli scientists tested vegetables for the epilepsy drug carbamazepine, they detected it in cucumbers, carrots, lettuce, and peppers. More surprisingly, people who ate the vegetables had a surge of the epilepsy drug in their urine—albeit in the nanograms.

BackgroundCurrent clinical assessments of Posttraumatic stress disorder (PTSD) rely solely on subjective symptoms and experiences reported by the patient, rather than objective biomarkers of the illness. Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. Here we aimed to classify individuals with PTSD versus controls using heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.MethodsWe analyzed brain MRI data from 3,527 structural-MRI; 2,502 resting state-fMRI; and 1,953 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls (TEHC and HC) using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality.ResultsWe found lower performance in classifying PTSD vs. controls with data from over 20 sites (60% test AUC for s-MRI, 59% for rs-fMRI and 56% for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history across all three modalities (75% AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance.ConclusionOur findings highlight the promise offered by machine learning methods for the diagnosis of patients with PTSD. The utility of brain biomarkers across three MRI modalities and the contribution of DVAE models for improving generalizability offers new insights into neural mechanisms involved in PTSD.Significance⍰Classifying PTSD from trauma-unexposed healthy controls (HC) using three imaging modalities performed well (∼75% AUC), but performance suffered markedly when classifying PTSD from trauma-exposed healthy controls (TEHC) using three imaging modalities (∼60% AUC).⍰Using deep learning for feature reduction (denoising variational auto-encoder; DVAE) dramatically reduced the number of features with no concomitant performance degradation.⍰Utilizing denoising variational autoencoder (DVAE) models improves generalizability across heterogeneous multi-site data compared with the traditional machine learning frameworks

Past research indicates strong monetary motives for gambling often elevate an individual’s risk of experiencing symptoms of gambling disorder, with personal relative deprivation (PRD) and upward mobility (UM) identified as key factors in this relationship. Nevertheless, few studies have examined how financial motives, PRD, and UM might interact for people playing modern video games—many of which offer financial incentives to encourage participation. Due to the overlap between gambling and (video) gaming, evidence suggests disordered gambling and disordered gaming might also share similarities. Therefore, the present study explored whether PRD influences associations between playing video games for financial motives, symptoms of Internet gaming disorder (IGD), and UM in two samples: 797 college students (Study 1) and 179 adult gamers over 25 years old (Study 2). Results from Study 1 revealed more PRD predicted more IGD symptoms, with higher financial gaming motives mediating the relationship. In Study 2, PRD also predicted IGD severity, but only coping motives appeared to mediate the positive association between PRD and IGD severity. In both samples, perceived UM inversely moderated the effect of PRD on one’s financial or coping gaming motives. These findings suggest financial motives for video games might lead to more problematic forms of participation for younger adults and negative perceptions of PRD and UM might interact, similar to gambling, to elevate a gamer’s vulnerability for IGD.

A number of studies of posttraumatic stress disorder (PTSD) report thinner cerebral cortical gyri using gyrus-based analysis or thinner foci within the gyri using vertex-based analysis. However, the locations of these findings are inconsistent across studies, and the spatial transformations required during vertex-based analysis may affect the focal findings. A mega-analysis using a large number of subjects from multiple PTSD studies could potentially identify more reproducible cortical thickness abnormalities. Investigating both the vertex and gyral thicknesses simultaneously may verify the vertex-based focal findings using gyral data without imposing any spatial transformation. Here we aggregated data from 24 international laboratories using ENIGMA standardized procedures for 949 adult PTSD patients and 1493 controls without PTSD (age 18 to 65 years). We examined whether gyral and vertex cortical thickness are (a) different between subjects with PTSD and controls and (b) associated with PTSD symptom severity in trauma-exposed subjects. Regions with overlapping thinner cortical gyri and thinner vertex clusters were located in frontal, temporal, parietal, and occipital cortices. Thinner right lateral orbitofrontal and right lingual gyri and concomitantly thinner vertex clusters in the anterior portions of both gyri were associated with PTSD symptom severity. Convergent findings in these locations suggest focally thinner cortex in these gyri, which may be involved in altered processing and regulation of emotion and sensory inputs underlying posttraumatic stress symptoms.

More Australians die in the hospital than in any other setting. This study aimed to (i) evaluate the quality of end-of-life (EOL) care in the hospital against an Australian National Standard, (ii) describe the characteristics of intensive care unit (ICU) clinician involvement in EOL care, and (iii) explore the demographic and clinical factors associated with quality of EOL care.A retrospective descriptive medical record audit was conducted on 297 adult inpatients who died in 2017 in a private acute care hospital in Melbourne, Australia. Data collected related to 20 'Processes of Care', considered to contribute to the quality of EOL care. The decedent sample was separated into three cohorts as per ICU clinician involvement.The median age of the sample was 81 (25th-75th percentile = 72-88) years. The median tally for EOL care quality was 16 (25th-75th percentile = 13-17) of 20 care processes. ICU clinicians were involved in 65.7% (n = 195) of cases; however, contact with the ICU outreach team or an ICU admission during the final inpatient stay was negatively associated with quality of EOL care (coefficient = -1.51 and -2.07, respectively). Longer length of stay was positively associated with EOL care (coefficient = .05). Specialist palliative care was involved in 53% of cases, but this was less likely for those admitted to the ICU (p .001). Evidence of social support, bereavement follow-up, and religious support were low across all cohorts.Statistically significant differences in the quality of EOL care and a negative association between ICU involvement and EOL care quality suggest opportunities for ICU outreach clinicians to facilitate discussion of care goals and the appropriateness of ICU admission. Advocating for inclusion of specialist palliative care and nonclinical support personnel in EOL care has merit. Future research is necessary to investigate the relationship between ICU intervention and EOL care quality.

Pavements, oddly enough, weren't really made for walking on. It's high time for a rethink, says Anthony King

Constipation in children is common and is a frequent cause for healthcare attendances in both primary and secondary care. The Bristol Stool Chart has become ubiquitous as an aid in the diagnosis and treatment of constipation, but many clinicians may not be aware of its origins or strengths and weaknesses. In this article, we outline the history and rationale behind the development of the Bristol Stool Chart and how it should be used in childhood constipation.

Against pacifist calls for peace at any price in Ukraine, Hans-Herbert Kögler argues that the west has a moral obligation to support Ukraine in its war against Russia. Kögler’s argument is well-made. However, he does not mention the war at all. This may be an oversight because while moral principles may be universal, in practice, the context defines how morals are applied. Drawing on Clausewitz’s concept of the Trinity, this response seeks to develop Kögler’s moral argument by examining the practical, military implications of the war. It argues that because the war is heavily urbanised, the west’s moral commitment is likely to be very deep and long.

Gallantry medals are invested with deep significance not only by the armed forces but also by civilian society. In the last decade, there has been a debate in sociology about whether the medallic regime has become post-heroic or whether it has professionalized. This article contributes to these debates by focusing on the topic of fraudulent medals. Fake medals are very rare; there has been one proven case in the United Kingdom in the last 20 years. However, precisely because fake medals are the exception, their pathologies illustrate the processes by which medals are actually awarded with particular clarity. This analysis of the fake medal shows that gallantry awards have professionalized; in the UK medals have become more meritocratic, recognizing skill not status. The awarding process is also more objective. Yet, its very professionalism is ironically vulnerable to a specific type of fraud by skilful but cynical citation writers.

to compare visual field (VF) progression between the 2 arms of the Treatment of Advanced Glaucoma Study (TAGS).Post hoc analysis of VF data from a 2-arm, multicenter, randomized controlled clinical trial.A total of 453 patients with newly diagnosed advanced open-angle glaucoma in at least 1 eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (n = 227) or medication in their index eye (n = 226) and followed-up for 2 years with 2 24-2 VF tests at baseline, 4, 12, and 24 months. Data were analyzed for participants with a reliable VF (false positive rate15%) at baseline and at least 2 other time points. Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5, and 2 dB) was compared using survival analysis.This study analyzed 211 eyes in the trabeculectomy first arm and 203 eyes in the medication first arm. The average RoP (estimate [95% credible intervals]) was -0.59 [-0.88, -0.31] dB/year in the medication first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy first arm. The difference was not significant (Bayesian P-value = .353). More eyes progressed in the medication first arm, but this difference was not significant.There was no significant difference in the average RoP at 2 years.

The body’s immune response to viruses has long been thought to spark autoimmune disease. A virus affecting millions of people could help researchers to finally know for sure. The body’s immune response to viruses has long been thought to spark autoimmune disease. A virus affecting millions of people could help researchers to finally know for sure.

Hew Strachan’s contribution to military history has been widely recognized. Signally, he brought a new global perspective to the study of the First World War, while simultaneously arguing for the irretrievably political nature of war. This article makes an unusual and implausible argument. It maintains that in addition to Strachan’s undoubted historical contribution, his work can be read as a form of sociology. Specifically, Strachan’s analysis of the politics of war and the armed forces highlights the way in which interest groups at every level influence defence policy and the conduct of war itself. By prioritizing political interests as a prime explanatory factor, Strachan has, perhaps unwittingly, developed a highly sophisticated sociology of war.

The covid-19 virus isn't the first coronavirus to jump from animals to humans. What can we learn from previous encounters, asks Anthony King.

In Soldiers of empire, Tarak Barkawi addresses a simple question: ‘How are soldiers made? Why do they fight?’ Barkawi is absolutely correct to highlight a question of profound importance to the his...

Constipation is common in childhood. It is a frequent presentation to primary care and common reason for referral to secondary and tertiary care. In the majority of cases, childhood constipation is idiopathic, with no significant underlying cause, but still presents a significant issue to patients, families and healthcare providers. We consider a case of idiopathic constipation, review the current evidence base for investigations and treatment and suggest practical management strategies.

Lessons learned from the vaccines against SARS-CoV-2 has encouraged research and vaccine development aimed at mustering strong T cell responses against the pathogen.

The muscles of elite endurance athletes boast high numbers of extra-efficient mitochondria. Unlocking the secrets of these cellular components could yield gains for future Olympians. The muscles of elite endurance athletes boast high numbers of extra-efficient mitochondria. Unlocking the secrets of these cellular components could yield gains for future Olympians.

Until COVID‐19, coronaviruses were largely overlooked by virologists. Yet, their abundance in mammalian species could cause new spillover events into humans. [Image: see text]

The current technique requires a person’s own cells, but using the cells of healthy donors could allow more people to benefit. The current technique requires a person’s own cells, but using the cells of healthy donors could allow more people to benefit.

As the first vaccine against the malaria parasite begins to roll out, scientists are working on a wide variety of alternatives that they hope will provide more protection. As the first vaccine against the malaria parasite begins to roll out, scientists are working on a wide variety of alternatives that they hope will provide more protection.