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Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

World Cup is a mega sports event enjoyed and built in the name of sport. However, as the community grows, World Cup becomes a sporting event and a political encounter. Each country is trying to be the best, and in order to achieve this, many seek mutual profit or increase power value during the event. Multivector Analysis was used to analyse social media content related to the Qatar 2022 World Cup. With the help of social media and Political Correctness, it becomes visible that these countries are trying to obtain their goals and match victory. Vulnerabilities, powers, and many faces accompany the condiments of the Qatar World Cup 2022. With a historical ancestry in FIFA, Political Correctness is like their anthems. Having a non-Western host would be a struggle against a larger country, resulting in a player exchange that allows them to become immigrants embroiled in heated political tensions because any country by nature still has a strong bias towards its land and its race.

Background and hypothesis Deficits in performing and interpreting communicative nonverbal behaviors, such as gesture, have been linked to varied psychopathology and dysfunction. Some evidence suggests that individuals at risk for psychosis have deficits in gesture interpretation and performance; however, individuals with internalizing disorders (eg, depression) may have similar deficits. No previous studies have examined whether gesture deficits in performance and interpretation are specific to those at risk for psychosis. Additionally, the underlying mechanisms (eg, cognition) and consequences (eg, functioning) of these deficits are poorly understood. Study design This study examined self-reported gesture interpretation (SRGI) and performance (SRGP) in those at clinical high risk for psychosis (CHR; N = 88), those with internalizing disorders (INT; N = 51), and healthy controls (HC; N = 53). Participants completed questionnaires, clinical interviews, and neurocognitive tasks. Study results Results indicated that the CHR group was characterized by significantly lower SRGI scores than the HC or INT groups (d = 0.41); there were no differences among groups in SRGP. Within CHR participants, greater deficits in SRGP were associated with lower verbal learning and memory (r = −.33), but not general intelligence or processing speed. Furthermore, gesture deficits were associated with higher cross-sectional risk for conversion to a full psychotic disorder in the CHR group. Conclusions Overall, these findings suggest that specific subdomains of gesture may reflect unique vulnerability for psychosis, self-report may be a viable assessment tool in understanding these phenomena, and gesture dysfunction may signal risk for transition to psychosis.

OBJECTIVE Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher’s exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Mechanisms underlying pain after axonal injury remain elusive. A small subgroup of patients experience pain after corneal refractive surgery, providing a human pain model after well-defined injury to axons. Here we analyze a mutation (P610T) in Nav1.7, a threshold sodium channel expressed in nociceptors, found in two siblings with persistent ocular pain after refractive surgery. We show that it impairs channel slow inactivation, thereby triggering inappropriate repetitive activity in trigeminal ganglion axons that signal eye pain.

Background: Hypertension-related increased arterial stiffness predicts development of target organ damage (TOD) and cardiovascular disease. We hypothesized that blood pressure (BP)–related increased arterial stiffness is present in youth with elevated BP and is associated with TOD. Methods: Participants were stratified by systolic BP into low- (systolic BP Results: Pulse wave velocity increased across groups. Aortic distensibility, distensibility coefficient, and compliance were greater in low than in the mid or high group. Significant determinants of arterial stiffness were sex, age, adiposity, BP, and LDL (low-density lipoprotein) cholesterol. Pulse wave velocity and aortic compliance were significantly associated with TOD (systolic and diastolic cardiac function and urine albumin/creatinine ratio) after controlling for BP. Conclusions: Higher arterial stiffness is associated with elevated BP and TOD in youth emphasizing the need for primary prevention of cardiovascular disease.

Facies variability of mudstones is likely greater than generally perceived, with important implications for their behaviour in major civil engineering, energy and waste disposal applications. Here, we explore this variability for the UK Oxford Clay, a widely studied Middle/Upper Jurassic mudstone. Evidence from wire-line logs, geochemistry, sequence stratigraphy and biofacies analyses are combined to reveal heterogeneity within the Peterborough Member (Lower Oxford Clay) and to explore the extent to which it blanketed basin features or responded dynamically to them. Thickness modelling suggests that the Mid North Sea High, formed by Mid Jurassic thermal doming, likely influenced sediment pathways, favouring thick sediment accumulation in the Wessex Basin, thinner successions across the East Midlands Shelf, and sediment starvation in the Weald Basin. Biofacies patterns, determined using a novel combination of detrended correspondence and cluster analysis, vary significantly and suggest a complex patchwork of environments related to local basin setting. The Type Section of the Peterborough Member seems to represent only a narrow range of conditions that influenced its deposition, and cautions against developing basin-scale models based on a few well exposed and heavily researched outcrop successions.

High photoluminescent InP/ZnS QDs synthesis by in situ H2S interface engineering.

Photocatalytic activity of titania is investigated during phenol degradation in standard water and brines. We demonstrate how solubilised chlorides can affect the hydroxyl radical formation and the photodegradation properties of titania.

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in May 2021. This summary describes how the vaccine worked in participants 12- to 15-years old. The part of the study described in the article is ongoing and expected to finish March 2023. This means that the final results may be different from the results included in this summary. What happened in this study? The part of the study described in this summary included participants 12- to 15-years old who had no serious health issues. The BNT162b2 vaccine had already been studied in participants 16 years of age or older. In this part of the study, the researchers wanted to find out: How effective and safe the vaccine was in participants 12- to 15-years old. What the immune response to the vaccine and the vaccine safety were like in 12- to 15-year-olds compared with 16- to 25-year-olds. How well the vaccine prevented SARS-CoV-2 infections in participants who received the vaccine compared to those who did not. This is also called efficacy of the BNT162b2 vaccine Half of the participants in this study received 2 injections of the BNT162b2 vaccine and half received 2 injections of a placebo in a muscle of the upper arm. The placebo looked like the BNT162b2 vaccine but did not have any active vaccine in it. What were the results? BNT162b2 had a favorable safety profile. The most common reactions were pain at the injection site, fatigue, and headache. None of the participants had serious reactions to the vaccine. The 12- to 15-year-old participants' immune system responses to the BNT162b2 vaccine were as good as or stronger than the 16- to 25-year-old participants' immune responses. The participants who received the BNT162b2 vaccine were less likely to get COVID-19 compared with the participants who got the placebo. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

This paper investigates the mechanical properties and microstructure of additively manufactured, continuous fiber reinforced composites made by the Continuous Fiber 3D Printing (CF3D®) process. We specifically investigate composites of GF-2, a high temperature thermosetting acrylic polymer, and T-1100, a high strength carbon fiber, with a 41.5% fiber volume fraction. The resulting composites have a longitudinal tensile modulus of 122 GPa and a strength of 1599 MPa, which is 89% and 55% of the theoretical value by rule of mixtures, respectively. This appears to be the highest strength additively manufactured composites to date, largely due to the high mechanical properties of the T-1100 fiber, low defects, and substantial fiber volume fraction. Comparable results are obtained for a cationic cure resin, CATPRO14. We optically measured the fiber–fiber contact surface area fraction of GF-2 and employing the unidirectional strength model of Karam to predict a strength efficiency of 0.6, which is in good agreement with mechanical estimate of 0.55. Comparing results with the efficiency factors of high fiber volume prepreg laminates, we determine the printing process yields composites with 88%–95% of the anticipated longitudinal modulus and 65%–70% of the anticipated longitudinal tensile strength of those processed by traditional methods. To extend the printing to multifunctional microvascular composites, we consider the mechanical implications of including sacrificial filaments of 100–300 μm within each tow. A modest decrease in longitudinal strength in proportion to the microchannel volume fraction is predicted, where the decrease is mainly attributed to the increased fiber-to-fiber interactions in more tightly packed tows.

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in September 2021. The part of the study described in the article began in July 2020 and is ongoing. This means that the final results may be different from the results included in this summary. What happened in this study? The participants in this study received 2 injections of either the BNT162b2 vaccine or a placebo, 21 days apart. The placebo looked like the BNT162b2 vaccine but had no active vaccine in it. None of the trial participants or study teams knew who received vaccine or placebo. What were the results? Most of the reactions to the injections were mild or moderate and lasted for a short period of time. The most common reactions were pain at the injection site, extreme tiredness (fatigue), and headache. These reactions usually happened in the first 7 days after receiving a vaccine dose. A small number of participants had severe reactions to the vaccine. Compared to participants who received the placebo, participants who received the BNT162b2 vaccine were much less likely to become ill if they were infected with the virus that causes COVID-19. The vaccine also had very good efficacy at preventing severe COVID-19. Participants in South Africa who received the BNT162b2 vaccine were less likely to become ill after infection with the beta variant of the virus compared to participants who received the placebo. The beta variant was very common in South Africa when the study was taking place. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )

The widespread comorbidity among psychiatric disorders demonstrated in epidemiological studies1–5 is mirrored by non-zero, positive genetic correlations from large-scale genetic studies6–10. To identify shared biological processes underpinning this observed phenotypic and genetic covariance and enhance molecular characterization of general psychiatric disorder liability11–13, we used several strategies aimed at uncovering pleiotropic, that is, cross-trait-associated, single-nucleotide polymorphisms (SNPs), genes and biological pathways. We conducted cross-trait meta-analysis on 12 psychiatric disorders to identify pleiotropic SNPs. The meta-analytic signal was driven by schizophrenia, hampering interpretation and joint biological characterization of the cross-trait meta-analytic signal. Subsequent pairwise comparisons of psychiatric disorders identified substantial pleiotropic overlap, but mainly among pairs of psychiatric disorders, and mainly at less stringent P-value thresholds. Only annotations related to evolutionarily conserved genomic regions were significant for multiple (9 out of 12) psychiatric disorders. Overall, identification of shared biological mechanisms remains challenging due to variation in power and genetic architecture between psychiatric disorders.

The monopoly capitalism literature has traditionally approached advertising from the vantage point of its role in sustaining the economic order. However, digitalised forms of advertising in contexts dominated by giant digital platform technology companies like Google, Facebook and Amazon are disrupting the existing order through a combination of subsidy and location effects, shored up by the capabilities of the new technology for real-time data collection on users. This poses significant challenges for theory and policy. In both respects the case is made for rehabilitating the earlier approach of Nicholas Kaldor, which emphasises both heterogeneity of advertising forms and questions of subsidy, to complement the dominant approaches of the monopoly capitalism school as exemplified by Paul Baran and Paul Sweezy on one side, and Keith Cowling on the other.

Background and Hypothesis: Persecutory delusions are among the most common delusions in schizophrenia and represent the extreme end of the paranoia continuum. Paranoia is accompanied by significant worry and distress. Identifying cognitive mechanisms underlying paranoia is critical for advancing treatment. We hypothesized that aberrant belief updating, which is related to paranoia in human and animal models, would also contribute to persecutory beliefs in individuals with schizophrenia. Study Design: Belief updating was assessed in 42 schizophrenia and 44 healthy participants, using a 3-option probabilistic reversal learning (3-PRL) task. Hierarchical Gaussian filter (HGF) was used to estimate computational parameters of belief updating. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS). Unusual thought content was measured with the Psychosis Symptom Rating Scale (PSYRATS) and the Peters et al. Delusions Inventory (PDI-21). Worry was measured using the Dunn Worry Questionnaire. Results: Consistent with prior work, paranoia was significantly associated with elevated win-switch rate, prior on volatility and sensitivity to volatility in both schizophrenia and across the whole sample. These relationships were specific to paranoia and did not extend to unusual thought content or measures of anxiety. We did, however, find a significant indirect effect of paranoia on the relationship between prior beliefs about volatility and worry. Conclusions: This work provides evidence that relationships between belief updating parameters and paranoia extend to schizophrenia, may be specific to persecutory beliefs, and contribute to theoretical models implicating worry in the maintenance of persecutory delusions.

This Special Issue of the Cambridge Journal of Economics (CJE) marks and celebrates forty years since the publication of Keith Cowling’s (1982) seminal Monopoly Capitalism, which synthesised, updated, and extended the earlier work of scholars such as Steindl (1952), Baran and Sweezy (1966), Hymer (1970, 1972) and Kalecki (1971). Since the publication of Monopoly Capitalism, the critical transformative event has been the latest (fourth) technological revolution and the emergence of Big Tech companies such as Facebook, Apple, Amazon, Netflix and Google (aka FAANGs), alongside Microsoft and so-called ‘gig’ or ‘sharing economy’ firms (such as Uber, Airbnb). While initially regarded as exemplars of the dynamics of contemporary capitalism, in recent years there has been a public backlash against Big Tech, and its impact and influence within the global economy. Indeed, several commentators have raised concerns that beneath the veneer of Big Tech lies potentially insidious business models and practices that have led to a rise in corporate power and the monopolisation of markets. These criticisms, however, largely ignore the contributions of earlier scholars of monopoly capitalism. This Special Issue addresses this oversight with a series of papers re-examining and extending the work of Cowling and others in the monopoly capitalism tradition, in the specific context of Big Tech. The Introduction opens with a portrait of Keith Cowling, as a person and his scholarly contribution to the field. It then provides a critical assessment of the papers in this Special Issue. In the Epilogue, we summarise and conclude.

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.

Background Imaging migraine premonitory studies show increased midbrain activation consistent with the ventral tegmental area, an area involved in pain modulation and hedonic feeding. We investigated ventral tegmental area pharmacological modulation effects on trigeminovascular processing and consequent glycemic levels, which could be involved in appetite changes in susceptible migraine patients. Methods Serotonin and pituitary adenylate cyclase-activating polypeptide receptors immunohistochemistry was performed in ventral tegmental area parabrachial pigmented nucleus of male Sprague Dawley rats. In vivo trigeminocervical complex neuronal responses to dura mater nociceptive electrical stimulation, and facial mechanical stimulation of the ophthalmic dermatome were recorded. Changes in trigeminocervical complex responses following ventral tegmental area parabrachial pigmented nucleus microinjection of glutamate, bicuculline, naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole were measured, and blood glucose levels assessed pre- and post-microinjection. Results Glutamatergic stimulation of ventral tegmental area parabrachial pigmented nucleus neurons reduced nociceptive and spontaneous trigeminocervical complex neuronal firing. Naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole inhibited trigeminovascular spontaneous activity, and trigeminocervical complex neuronal responses to dural-evoked electrical and mechanical noxious stimulation. Trigeminovascular sensory processing through modulation of the ventral tegmental area parabrachial pigmented nucleus resulted in reduced circulating glucose levels. Conclusion Pharmacological modulation of ventral tegmental area parabrachial pigmented nucleus neurons elicits changes in trigeminovascular sensory processing. The interplay between ventral tegmental area parabrachial pigmented nucleus activity and the sensory processing by the trigeminovascular system may be relevant to understand associated sensory and homeostatic symptoms in susceptible migraine patients.

Anthropogenic alteration of physical habitat structure in streams and rivers is increasingly recognized as a major cause of impairment worldwide. As part of their assessment of the status and trends in the condition of rivers and streams in the U.S., the U.S. Environmental Protection Agency's (USEPA) National Aquatic Resource Surveys (NARS) quantify and monitor channel size and slope, substrate size and stability, instream habitat complexity and cover, riparian vegetation cover and structure, anthropogenic disturbance activities, and channel-riparian interaction. Like biological assemblages and water chemistry, physical habitat is strongly controlled by natural geoclimatic factors that can obscure or amplify the influence of human activities. We developed a systematic approach to estimate the deviation of observed river and stream physical habitat from that expected in least-disturbed reference conditions. We applied this approach to calculate indices of anthropogenic alteration of three aspects of physical habitat condition in the conterminous U.S. (CONUS): streambed sediment size and stability, riparian vegetation cover, and instream habitat complexity. The precision and responsiveness of these indices led the USEPA to use them to evaluate physical habitat condition in CONUS rivers and streams. The scores of these indices systematically decreased with greater anthropogenic disturbance at river and stream sites in the CONUS and within ecoregions, which we interpret as a response of these physical habitat indices to anthropogenic influences. Although anthropogenic activities negatively influenced all three physical habitat indices in the least-disturbed sites within most ecoregions, natural geoclimatic and geomorphic factors were the dominant influences. For sites over the full range of anthropogenic disturbance, analyses of observed/expected sediment characteristics showed augmented flood flows and basin and riparian agriculture to be the leading predictors of streambed instability and excess fine sediments. Similarly, basin and riparian agriculture and non-agricultural riparian land uses were the leading predictors of reduced riparian vegetation cover complexity in the CONUS and within ecoregions. In turn, these reductions in riparian vegetation cover and complexity, combined with reduced summer low flows, were the leading predictors of instream habitat simplification. We conclude that quantitative measures of physical habitat structure are useful and important indicators of the impacts of human activities on stream and river condition.

Taxonomic inconsistency in species-level identifications has constrained use of diatoms as biological indicators in aquatic assessments. We addressed this problem by developing diatom multimetric indices (MMIs) of ecological condition using genus-level taxonomy and trait-based autecological information. The MMIs were designed to assess river and stream chemical, physical and biological condition across the conterminous United States. Trait-based approaches have the advantage of using both species-level and genus-level data, which require less effort and expense to acquire than traditional species-based approaches and eliminate the persistent taxonomic biases introduced over vast geographic extents. For large-extent assessment programs that require multiple taxonomic laboratories to process samples, such as the United States Environmental Protection Agency's (U.S. EPA's) National Rivers and Streams Assessment (NRSA), the trait approach can eliminate discrepancies in species-level identification or nomenclature that hinder diatom data interpretation. We developed trait-based MMIs using NRSA data for each of the three large ecoregions across the U.S. - the East, Plains, and West. All three MMIs performed well in discriminating least-disturbed from most-disturbed sites. The MMI for the East had the greatest discrimination ability, followed by MMIs for the Plains and West, respectively. The performance of the MMIs was comparable to that observed in existing NRSA fish and macroinvertebrate MMIs. Our research shows that trait-based diatom indices constructed on genus-level taxonomy can be effective for large-scale assessments, and may also allow programs such as NRSA to assess trends in freshwater condition retrospectively, by revisiting older diatom datasets. Moreover, our genus-based approach facilitates including of diatoms into other assessment programs that have limited monitoring resources.

This article examines the disruptive role that fog and associated weather conditions play in human livelihood activities undertaken on and around the Grand Banks of the north-western Atlantic, the affective atmosphere they create and their effect on human participants. After an introduction to the position and nature of the Grand Banks, relevant weather systems, ocean currents and iceberg trajectories through the region, the article profiles the nature of fishing (and, subsequently, oil extraction) in the area, of the precarity of livelihood activities undertaken and their reflection and inscription in various media. This approach identifies the manner in which aquapelagos (integrated terrestrial and marine systems) are not necessarily safe or stable entities – even in the shortest of terms – and can, indeed, represent assemblages in which humans are stressed and threatened. Within this, the case study examines the manner in which fog is not so much an uncomfortable intrusion into an otherwise manageable industrial operation as a key characteristic to be accommodated. The experience of fog is crucial to the social experience of the Grand Banks and of the aquapelago that is constituted around it. Substantial consideration is also given to the atmospherics of Grand Banks fog in literature and visual art and of the imaginative space created for it.

We introduce and study a new optimization problem on digraphs, termed Maximum Weighted Digraph Partition (MWDP) problem. We prove three complexity dichotomies for MWDP: on arbitrary digraphs, on oriented digraphs, and on symmetric digraphs. We demonstrate applications of the dichotomies for binary-action polymatrix games and several graph theory problems., arXiv admin note: substantial text overlap with arXiv:2305.07124

This study aims to describe end-of-life (EOL) care in older patients with cancer and investigate the association between geriatric assessment (GA) results and specialized palliative care (SPC) use. Older patients with a new cancer diagnosis (2009–2015) originally included in a previous multicentric study were selected if they died before the end of follow-up (2019). At the time of cancer diagnosis, patients underwent geriatric screening with Geriatric 8 (G8) followed by GA in case of a G8 score ≤14/17. These data were linked to the cancer registry and healthcare reimbursement data for follow-up. EOL care was assessed in the last three months before death, and associations were analyzed using logistic regression. A total of 3546 deceased older patients with cancer with a median age of 79 years at diagnosis were included. Breast, colon, and lung cancer were the most common diagnoses. In the last three months of life, 76.3% were hospitalized, 49.1% had an emergency department visit, and 43.5% received SPC. In total, 55.0% died in the hospital (38.5% in a non-palliative care unit and 16.4% in a palliative care unit). In multivariable analyses, functional and cognitive impairment at cancer diagnosis was associated with less SPC. Further research on optimizing EOL healthcare utilization and broadening access to SPC is needed.

This study aimed to quantify the confirmation of gallstones on ultrasound (US) in patients with suspicion of gallstone disease. To aid general practitioners (GPs) in diagnostic workup, a model to predict gallstones was developed. A prospective cohort study was conducted in two Dutch general hospitals. Patients (≥18 years) were eligible for inclusion when referred by GPs for US with suspicion of gallstones. The primary outcome was the confirmation of gallstones on US. A multivariable regression model was developed to predict the presence of gallstones. In total, 177 patients were referred with a clinical suspicion of gallstones. Gallstones were found in 64 of 177 patients (36.2%). Patients with gallstones reported higher pain scores (VAS 8.0 vs. 6.0, p < 0.001), less frequent pain (21.9% vs. 54.9%, p < 0.001), and more often met criteria for biliary colic (62.5% vs. 44.2%, p = 0.023). Predictors for the presence of gallstones were a higher pain score, frequency of pain less than weekly, biliary colic, and an absence of heartburn. The model showed good discrimination between patients with and without gallstones (C-statistic 0.73, range: 0.68–0.76). Clinical diagnosis of symptomatic gallstone disease is challenging. The model developed in this study may aid in the selection of patients for referral and improve treatment related outcomes.

Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and resistance. This study aimed to develop an intravenous ganciclovir population pharmacokinetic model for post-alloHCT patients and to determine dosing regimens likely to achieve suggested therapeutic exposure targets. We performed a prospective observational single-center pharmacokinetic study in adult alloHCT patients requiring treatment with intravenous ganciclovir for CMV viremia or disease. Samples were analyzed using a validated ultraperformance liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. Twenty patients aged 18 to 69 years were included in the study. A 2-compartment model with linear elimination from the central compartment and between occasion variability best described the data. Incorporating creatinine clearance (CLCR) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and presence of continuous renal replacement therapy as covariates for ganciclovir clearance improved the model. Compared to current dosing recommendations, simulations demonstrated loading doses were required to achieve a target AUC24 of 80 to 120 mg.h/L on day 1 of induction therapy. Increased individualization of post-loading induction and maintenance doses based on CLCR is required to achieve the suggested exposures for efficacy (AUC24 >80/>40 mg.h/L for induction/maintenance) while remaining below the exposure thresholds for toxicity (AUC24

Refereed/Peer-reviewed Background: Different software applications have been developed to support health care professionals in individualized drug dosing. However, their translation into clinical practice is limited, partly because of poor usability and integration into workflow, which can be attributed to the limited involvement of health care professionals in the development and implementation of drug dosing software. This study applied codesign principles to inform the design of a drug dosing software to address barriers in therapeutic drug monitoring using vancomycin as an example. Methods: Three workshops (face-to-face and online) were conducted by design researchers with pharmacists and prescribers. User journey storyboards, user personas, and prototyping tools were used to explore existing barriers to practice and opportunities for innovation through drug dosing software design. A prototype of the software interface was developed for further evaluation. Results: Health care professionals (11 hospital pharmacists and 6 prescribers) with ≥2 years of clinical experience were recruited. Confidence and software usability emerged as the main themes. Participants identified a lack of confidence in vancomycin dosing and pharmacokinetic understanding and difficulty in accessing practice guidelines as key barriers that could be addressed through software implementation. Accessibility to information (eg, guidelines and pharmacokinetic resources) and information presentation (eg, graphical) within the dosing software were dependent on the needs and experience of the user. A software prototype with a speedometer-dial visual to convey optimal doses was well received by participants. Conclusions: The perspectives of health care professionals highlight the need for drug dosing software to be user centered and adaptable to the needs and workflow of end users. Continuous engagement with stakeholders on tool usability, training, and education is needed to promote the implementation in practice.

A recent paper in

Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci. This extreme polygenicity suggested that many more loci remain to be discovered. The current study almost doubled the sample size to 593,724 cases and 1,771,286 controls, thereby increasing statistical power, and identified 554 risk loci (including 364 novel loci). To capitalize on this large number of loci, we propose a novel strategy to prioritize genes using external biological resources and functional interactions between genes across risk loci. Of all 3,898 genes naively implicated from the risk loci, we prioritize 289 and find brain-tissue expression specificity and enrichment in specific gene sets of synaptic signaling functions and neuronal differentiation. We show that this novel gene prioritization strategy yields specific hypotheses on underlying mechanisms of insomnia that would have been missed by traditional approaches.

The hippocampus and cingulate gyrus are strongly interconnected brain regions that have been implicated in the neurobiology of post-traumatic stress disorder (PTSD). These brain structures are comprised of functionally distinct subregions that may contribute to the expression of PTSD symptoms or associated cardio-metabolic markers, but have not been well investigated in prior studies.Two divisions of the cingulate cortex (i.e., rostral and caudal) and 11 hippocampal subregions were investigated in 22 male combat-exposed veterans with PTSD and 22 male trauma-exposed veteran controls (TC). Cardio-metabolic measures included cholesterol, body mass index, and mean arterial pressure.Individuals with PTSD had less caudal cingulate area compared to TC even after controlling for caudal cingulate thickness. Total hippocampus volume was lower in PTSD compared to TC, accounted for by differences in CA1-CA4, granule cell layer of the dentate gyrus, molecular layer, and subiculum. Individuals with PTSD had higher mean arterial pressure compared to TC, which correlated with hippocampus volume only in the PTSD group.Sample size, cross-sectional analysis, no control for medications and findings limited to males.These data demonstrate preferential involvement of caudal cingulate area (vs. thickness) and hippocampus subregions in PTSD. The inverse association between hippocampus volume and mean arterial pressure may contribute to accelerated aging known to be associated with PTSD.

Eleanor Harris Rowland Wembridge, one of the first women psychologists in the country, advocated tirelessly for the delivery of psychological services to enhance the lives of marginalized girls and women. Eleanor launched forward professionally with her doctorate at the young age of 22 and began work 5 years later at the Bedford reformatory that would ultimately lead to the first published correctional psychology research study. This precedent sets the historical marker at the interface of offender assessment, programs, and reentry. A harbinger of the scientist-practitioner model in clinical psychology, Eleanor retained a scholarly approach to her public service psychology work in various academic, correctional, forensic, and military settings across the country. In those public service settings, she heard and reflected the voices of the underserved through her distinctive advocacy, service, and justice writing. Eleanor left behind a largely invisible, but important legacy inside the walls of the correctional institution as an advocate for programs for justice-involved women, and outside the walls of corrections as a model for women psychologists. She is a remarkable figure in the history of public service psychology, and this article eliminates the problem of her absence from the general history of psychology literature. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Plasma separation cards represent a viable approach for expanding testing capabilities away from clinical settings by generating cell-free plasma with minimal user intervention. These devices typically comprise a basic structure of plasma separation membrane (PSM), unconstrained porous collection pad, and utilize either (i) lateral or (ii) vertical fluidic pathways for separating plasma. Unfortunately, these configurations are highly susceptible to (i) inconsistent sampling volume due to differences in patient hematocrit or (ii) severe contamination due to leakage of red blood cells (RBCs) or release of hemoglobin (i.e., hemolysis). Herein, we combine the enhanced sampling of our previously reported patterned dried blood spot (pDBS) cards with an assembly of porous separation materials to produce a patterned dried plasma spot (pDPS) card for direct processing and storage of cell-free plasma. Linking both vertical separation and lateral distribution of plasma yields discrete plasma collection zones that are spatially protected from potential contamination due to hemolysis and an inlet zone enriched with blood cells for additional testing. We evaluate the versatility of this card by quantitation of three classes of analytes and techniques including: (i) soluble transferrin receptor by enzyme-linked immunosorbent assay (ELISA), (ii) potassium by inductively coupled plasma atomic emission spectroscopy (ICP-AES), and (iii) 18S rRNA by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). We achieve quantitative recovery of each class of analyte with no statistically significant difference between dried and liquid reference samples. We anticipate that this sampling approach can be applied broadly to improve access to critical blood testing in resource limited settings or at the point of care.

We contribute to the literature on cluster dynamics to show that the outcome for declining industrial clusters are not necessarily restricted to death or renewal or replacement. We do so by considering upward and downward causation pressures in the evolution of the North Staffordshire’s ceramics cluster and the role of actors, their visions and the modification of their assets as influenced by both local knowledge sharing and exposure to ‘global buzz’ at international trade fairs. Efforts by cluster-level actors to reinvigorate the cluster appear to be having an effect, and we highlight the types of knowledge being infused into the cluster through these activities. We find the cluster is experiencing two different pathways simultaneously: the first is one of renewal, where traditional ceramicware firms have been supported by cluster-level actors to find new knowledge and make incremental innovations to support the aesthetic appeal of their product offerings and market reach; the second is a form of cluster exaptation where technical ceramics firms have moved onto a pathway with radical innovative potential associated with the properties of ceramics as advanced materials. We conclude with some policy suggestions for the revival of declining clusters.

To document the prevalence of, and the effect on outcomes, operatively treated bilateral femur fractures treated using contemporary treatments.A retrospective cohort using data from the National Trauma Data Bank.In total, 119,213 patients in the National Trauma Data Bank between the years 2007 and 2015 who had operatively treated femoral shaft fractures.Complication rates, hospital length of stay (LOS), days in the intensive care unit (ICU LOS), days on a ventilator, and mortality rates.Patients with bilateral femur fractures had increased overall complications (0.74 vs. 0.50, P0.0001), a longer LOS (14.3 vs. 9.2, P0.0001), an increased ICU LOS (5.3 vs. 2.4, P0.0001), and more days on a ventilator (3.1 vs. 1.3, P0.0001), when compared with unilateral fractures. Bilateral femoral shaft fractures were independently associated with worse outcomes in all primary domains when adjusted by Injury Severity Score (P0.0001), apart from mortality rates. Age-adjusted bilateral injuries were independently associated with worse outcomes in all primary domains (P0.0001) except for the overall complication rate. A delay in fracture fixation beyond 24 hours was associated with increased mortality (P0.0001) and worse outcomes for all other primary measures (P0.0001 to P = 0.0278) for all patients.Bilateral femoral shaft fractures are an independent marker for increased hospital and ICU LOS, number of days on a ventilator, and increased complication rates, when compared with unilateral injuries and adjusted for age and Injury Severity Score. Timely definitive fixation, in a physiologically appropriate patient, is critical because a delay is associated with worse inpatient outcome measures and higher mortality rates.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

This study evaluated whether lifetime traumatic stress compared to deployment-related traumatic stress differentially affected the likelihood of insomnia in military personnel.Data were obtained from the Army Study to Assess Risk and Resilience in Servicemembers (unweighted N = 21,499; weighted N = 670,335; 18-61 years; 13.5% Female). DSM-5 criteria were applied to the Brief Insomnia Questionnaire to determine past month insomnia diagnostic status. A lifetime stress survey was used to assess traumatic stress encountered outside of the military, and a deployment-related stress survey assessed for various types of deployment-related traumatic stress.Adjusting for sex and psychiatric disorders, lifetime traumatic stress increased the prevalence for insomnia among those who endorsed combat death of close friend or relative, 1.021 (95% CI, 1.02-1.02), followed by those who reported other experiences that put them at risk of death or serious injury, 1.013 (95% CI, 1.01-1.01), whereas deployment-related traumatic stress showed that the prevalence for insomnia was highest for those who reported being sexually assaulted or raped, 1.059 (95% CI, 1.04-1.08), followed by those who endorsed being hazed or bullied by one or more members of their unit 1.042 (95% CI, 1.04-1.05).The cross-sectional nature of the assessment limits causal inferences and there was no clinician determined diagnosis for insomnia.Findings suggest that traumas over both one's lifetime and during deployment are associated with a higher prevalence for insomnia among Army soldiers. Results highlight the importance of considering both lifetime and deployment traumas into mental health assessment and treatment for active-duty soldiers.

The COVID-19 pandemic created pressure to implement telepsychiatry across practice models.We sought to evaluate the overall success of this change and to identify what types of practice settings, provider groups, and patient groups were best served by telepsychiatry and telepsychotherapy utilization. We were particularly interested in how providers of consultation-liaison psychiatry adapted to remote care.An anonymous provider survey querying demographics, education, training, technological experience, practice setting, treatment modalities, patient groups, transition process, and outcomes was made openly available via social media and professional listservs. We used multivariable regression modeling to evaluate for predictors of the positive outcomes of overall satisfaction, subjective ability to diagnose and treat patients adequately using exclusively telepsychiatric platforms, and patient satisfaction by proxy.Three hundred thirty-three respondents, mostly young (59.4% younger than 50 years), female (69.7%), and physicians (67.9%), completed the survey. One hundred ninety-seven (59.1%) worked in consultation-liaison psychiatry. Of the total, 85.9% gave affirmative answers to overall satisfaction. Multivariable linear regression models found that satisfaction was predicted by general comfort with technology (P0.001), but negatively correlated with having technical issues (P0.001), a priori skepticism (P0.001), clinician being male (P = 0.004), and treating LGBTQ+ patients (P = 0.022). Completeness was associated with having training in telehealth (P = 0.039) and general comfort with technology (P 0.001) but negatively associated with treating LGBTQ+ patients (P = 0.024) or inpatients (P = 0.002). Patient satisfaction by proxy was positively associated with general comfort with technology (P0.001) and the respondent being a nonphysician (P = 0.004) and negatively associated with encountering a technical issue (P = 0.013) or treating inpatients (P = 0.045). Consultation-liaison psychiatrists had similar results overall and were more likely to have other staff assist in making televisits effective (mean [standard deviation]: -1.25 [3.57] versus -2.76 [3.27], P 0.001) especially if consultative (mean [standard deviation]: -0.87 [3.67] versus -2.39 [3.01], P = 0.010).This study suggests high rates of overall satisfaction in telepsychiatry adoption, even in consultation-liaison psychiatry. There is distinct benefit in bolstering training, providing technical support, and addressing skepticism. Future research should include patient surveys and control groups and should focus on vulnerable populations such as sexual and gender minorities.