The dose-effect relationship of six stimulation parameters with rTMS over left DLPFC on treatment-resistant depression: a systematic review and meta-analysis.

This study aimed to evaluate the association of the six parameters, namely stimulation intensity, stimulation frequency, pulses per session, treatment duration, number of sessions, and total number of pulses with the efficacy of conventional transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex for patients with treatment-resistant depression (TRD). A random-effects dose-response meta-analysis of blinded randomized controlled trials (RCTs) involving 2391 participants were conducted to examine the dose-effect relationship of six stimulation parameters. Any of the six parameters significantly individually predicted proportion of variance in efficacy: pulses per session (R²=52.7%), treatment duration (R²=51.2%), total sessions (R²=50.9%), frequency (R²=49.6%), total pulses (R²=49.5%), and intensity (R²= 40.4%). Besides, we identified frequency as a potential parameter interacting with the other five parameters, resulting in a significant increase in variance(ΔR2) ranging from 5.0% to 16.7%. Finally, we found that RCTs using frequency > 10Hz compared to those of 10Hz showed better dose-effect relationships. We conclude that the six stimulation parameters significantly predict the dose-effect relationship of conventional rTMS on TRD. Besides, higher stimulation frequency, higher stimulation intensity, and adequate number of pulses were associated with treatment efficacy.

Angiotensin-(1-12): Does It Exist? A Critical Evaluation in Humans, Rats, and Mice.

BACKGROUND: Angiotensin-(1-12), measured by a self-developed, polyclonal antibody-based radioimmunoassay, has been suggested to act as an alternative precursor of angiotensin II. A more reliable detection method would be liquid chromatography-tandem mass spectrometry. METHODS: We set up the quantification of human and murine angiotensin-(1-12) by liquid chromatography-tandem mass spectrometry and then used this method to measure angiotensin-(1-12) in human and mouse blood samples, as well as in mouse brain and kidney. We also verified ex vivo angiotensin-(1-12) generation and metabolism in human blood samples incubated at 37 °C. RESULTS: Stabilization of blood in guanidine hydrochloride was chosen for sample collection since this allowed full recovery of spiked angiotensin-(1-12). Angiotensin-(1-12) was undetectable in human blood samples when incubating nonstabilized plasma at 37 °C, while angiotensin-(1-12) added to nonstabilized human plasma disappeared within 10 minutes. Stabilized human blood samples contained angiotensin II, while angiotensin-(1-12) was undetectable. Blood, hearts, and kidneys, but not brains, of wild-type mice and rats contained detectable levels of angiotensin II, while angiotensin-(1-12) was undetectable. In renin knockout mice, all angiotensins, including angiotensin-(1-12), were undetectable at all sites, despite a 50% rise in angiotensinogen. Angiotensin-(1-12) metabolism in human blood plasma was not affected by renin inhibition. Yet, blockade of angiotensin-converting enzyme and aminopeptidase A, but not of chymase, neutral endopeptidase, or prolyl oligopeptidase, prolonged the half-life of angiotensin-(1-12), and angiotensin-converting enzyme inhibition prevented the formation of angiotensin II. CONCLUSIONS: We were unable to detect intact angiotensin-(1-12) in humans or mice, either in blood or tissue, suggesting that this metabolite is an unlikely source of endogenous angiotensins.

Prognostic value of EndoPredict test in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer screened for the randomized, double-blind, phase III UNIRAD trial.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of the multigene EndoPredict test in prospectively collected data of patients screened for the randomized, double-blind, phase III UNIRAD trial, which evaluated the addition of everolimus to adjuvant endocrine therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. PATIENTS AND METHODS: Patients were classified into low or high risk according to the EPclin score, consisting of a 12-gene molecular score combined with tumor size and nodal status. Association of the EPclin score with disease-free survival (DFS) and distant metastasis-free survival (DMFS) was evaluated using Kaplan-Meier estimates. The independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics. RESULTS: EndoPredict test results were available for 768 patients: 663 patients classified as EPclin high risk (EPCH) and 105 patients as EPclin low risk (EPCL). Median follow-up was 70 months (range 1-172 months). For the 429 EPCH randomized patients, there was no significant difference in DFS between treatment arms. The 60-month relapse rate for patients in the EPCL and EPCH groups was 0% and 7%, respectively. Hazard ratio (HR) supposing continuous EPclin score was 1.87 [95% confidence interval (CI) 1.4-2.5, P < 0.0001]. This prognostic effect remained significant when assessed in a Cox model adjusting on tumor size, number of positive nodes and tumor grade (HR 1.52, 95% CI 1.09-2.13, P = 0.0141). The 60-month DMFS for patients in the EPCL and EPCH groups was 100% and 94%, respectively (adjusted HR 8.10, 95% CI 1.1-59.1, P < 0.0001). CONCLUSIONS: The results confirm the value of EPclin score as an independent prognostic parameter in node-positive, hormone receptor-positive, HER2-negative early breast cancer patients receiving standard adjuvant treatment. EPclin score can be used to identify patients at higher risk of recurrence who may warrant additional systemic treatments.

New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.

Gait Training Based-Motor Imagery and EEG Neurofeedback in Lokomat: A Clinical Intervention with Complete Spinal Cord Injury Individuals.

Robotic systems, such as Lokomat® have shown promising results in people with severe motor impairments, who suffered a stroke or other neurological damage. Robotic devices have also been used by people with more challenging damages, such as Spinal Cord Injury (SCI), using feedback strategies that provide information about the brain activity in real-time. This study proposes a novel Motor Imagery (MI)-based Electroencephalogram (EEG) Visual Neurofeedback (VNFB) system for Lokomat® to teach individuals how to modulate their own µ (8-12 Hz) and ß (15-20 Hz) rhythms during passive walking. Two individuals with complete SCI tested our VNFB system completing a total of 12 sessions, each on different days. For evaluation, clinical outcomes before and after the intervention and brain connectivity were analyzed. As findings, the sensitivity related to light touch and painful discrimination increased for both individuals. Furthermore, an improvement in neurogenic bladder and bowel functions was observed according to the American Spinal Injury Association Impairment Scale, Neurogenic Bladder Symptom Score, and Gastrointestinal Symptom Rating Scale. Moreover, brain connectivity between different EEG locations significantly (p <0.05) increased, mainly in the motor cortex. As other highlight, both SCI individuals enhanced their µ rhythm, suggesting motor learning. These results indicate that our gait training approach may have substantial clinical benefits in complete SCI individuals.

Pooled multicolour tagging for visualizing subcellular protein dynamics.

Imaging-based methods are widely used for studying the subcellular localization of proteins in living cells. While routine for individual proteins, global monitoring of protein dynamics following perturbation typically relies on arrayed panels of fluorescently tagged cell lines, limiting throughput and scalability. Here, we describe a strategy that combines high-throughput microscopy, computer vision and machine learning to detect perturbation-induced changes in multicolour tagged visual proteomics cell (vpCell) pools. We use genome-wide and cancer-focused intron-targeting sgRNA libraries to generate vpCell pools and a large, arrayed collection of clones each expressing two different endogenously tagged fluorescent proteins. Individual clones can be identified in vpCell pools by image analysis using the localization patterns and expression level of the tagged proteins as visual barcodes, enabling simultaneous live-cell monitoring of large sets of proteins. To demonstrate broad applicability and scale, we test the effects of antiproliferative compounds on a pool with cancer-related proteins, on which we identify widespread protein localization changes and new inhibitors of the nuclear import/export machinery. The time-resolved characterization of changes in subcellular localization and abundance of proteins upon perturbation in a pooled format highlights the power of the vpCell approach for drug discovery and mechanism-of-action studies.

Antibody-drug conjugates in lung and breast cancer: Current evidence and future directions - a position statement from the ETOP IBCSG Partners Foundation.

Following the approval of the first antibody-drug conjugates (ADCs) in the early 2000s, development has increased dramatically, with 14 ADCs now approved and >100 in clinical development. In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 (datopotamab deruxtecan and sacituzumab govitecan [SG]) and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing. Thus, in the coming years, we are likely to see significant changes to treatment algorithms. As the number of available ADCs increases, biomarkers (of response and resistance) to better select patients are urgently needed. Biopsy sample collection at the time of treatment selection and incorporation of translational research into clinical trial designs are therefore critical. Biopsy samples taken peri- and post-ADC treatment combined with functional genomics screens could provide insights into response/resistance mechanisms as well as the impact of ADCs on tumour biology and the tumour microenvironment, which could improve understanding of the mechanisms underlying these complex molecules. Many ADCs are undergoing evaluation as combination therapy, but a high bar should be set to progress clinical evaluation of any ADC-based combination, particularly considering the high cost and potential toxicity implications. Efforts to optimise ADC dosing/duration, sequencing and the potential for ADC rechallenge are also important, especially considering sustainability aspects. The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.

The impact of psychosocial adversity on brain and behaviour: an overview of existing knowledge and directions for future research.

Environmental experiences play a critical role in shaping the structure and function of the brain. Its plasticity in response to different external stimuli has been the focus of research efforts for decades. In this review, we explore the effects of adversity on brain's structure and function and its implications for brain development, adaptation, and the emergence of mental health disorders. We are focusing on adverse events that emerge from the immediate surroundings of an individual, i.e., microenvironment. They include childhood maltreatment, peer victimisation, social isolation, affective loss, domestic conflict, and poverty. We also take into consideration exposure to environmental toxins. Converging evidence suggests that different types of adversity may share common underlying mechanisms while also exhibiting unique pathways. However, they are often studied in isolation, limiting our understanding of their combined effects and the interconnected nature of their impact. The integration of large, deep-phenotyping datasets and collaborative efforts can provide sufficient power to analyse high dimensional environmental profiles and advance the systematic mapping of neuronal mechanisms. This review provides a background for future research, highlighting the importance of understanding the cumulative impact of various adversities, through data-driven approaches and integrative multimodal analysis techniques.

Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Atrial Fibrillation in Critically Ill Patients: Incidence and Outcomes.

BACKGROUND: Atrial fibrillation (AF), either chronic or new onset, is common in critically ill patients. Its epidemiology and relationship with clinical outcomes are poorly known. OBJECTIVE: To understand the burden of AF in patients admitted to the ICU and its impact on patients' outcomes. METHODS: This is a single-center, retrospective cohort study evaluating all patients with AF admitted to a non-cardiac intensive care unit over the course of 54 months. Clinical outcomes were evaluated in the short (hospital discharge) and long term (two-year follow-up). The hazard ratio (HR) with 95% CI was computed for the whole population as well as for propensity score-matched patients, with or without AF. RESULTS: A total of 1357 patients were screened (59.1% male), with a mean age of 75 ± 15.2 years, length of intensive care unit stay of 4.7 ± 5.1 days, and hospital mortality of 26%. A diagnosis of AF was found in 215 patients (15.8%), 142 of whom had chronic AF. The hospital all-cause mortality was similar in patients with chronic or new-onset AF (31% vs. 28.8%, p = 0.779). Patients with AF had higher in-hospital, one-year, and two-year crude mortality (30.2% vs. 22.9%, p = 0.024; 47.9% vs. 35.3%, p = 0.001; 52.6% vs. 38.4%, p < 0.001). However, after propensity score matching (N = 213), this difference was no longer significant for in-hospital mortality (OR: 1.17; 95% CI: 0.77-1.79), one-year mortality (OR: 1.38; 95% CI: 0.94-2.03), or two-year mortality (OR: 1.30; 95% CI: 0.89-1.90). CONCLUSIONS: In ICU patients, the prevalence of AF, either chronic or new-onset, was 15.8%, and these patients had higher crude mortality. However, after adjustment for age and severity on admission, no significant differences were found in the short- and long-term mortality.

Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

Water Stress Influences Phytoestrogen Levels in Red Clover (Trifolium pratense) but Not Kura Clover (T. ambiguum).

Some forage legumes synthesize phytoestrogens. We conducted a glasshouse study to investigate how water stress (drought and waterlogging) influences phytoestrogen accumulation in red clover and kura clover. Compared to the red clover control, the 20 day drought resulted in an over 100% increase in the phytoestrogens formononetin and biochanin A, which together accounted for 91-96% of the total phytoestrogens measured. Waterlogging resulted in elevated concentrations of daidzein, genistein, and prunetin but not formononetin or biochanin A. Concentrations of phytoestrogens in kura clover were low or undetectable, regardless of water stress treatment. Leaf water potential was the most explanatory single-predictor of the variation in concentrations of formononetin, biochanin A, and total phytoestrogens in red clover. These results suggest that drought-stressed red clover may have higher potential to lead to estrogenic effects in ruminant livestock and that kura clover is a promising alternative low- or no-phytoestrogen perennial forage legume.

Deciphering global patterns of forest canopy rainfall interception (FCRI): A synthesis of geographical, forest species, and methodological influences.

Forest canopy rainfall interception (FRCI) is an essential hydrological process that governs water and biogeochemical cycles in forest ecosystems. Identifying patterns and relationships of FCRI using a systematic review is key to improving our knowledge supporting new experiment research, modeling, and application. In this meta-analysis, we aimed to delineate the canopy interception (CI), throughfall (TF), and stemflow (SF) concerning geographical and forest variables and experimental methodologies. We leveraged peer-reviewed 170 articles across 234 sites globally, extracting TF, CI, SF, geographical, forest, and experimental aspects. We applied multivariate statistical procedures to discern the principal influences on TF, CI, and SF and examined their multicollinearity. In addition, we developed Generalized Linear Models (GLM) for CI and TF. Global TF experiments indicate that the predominant rainfall devices, number of sample trees, number of events, and monitoring length are 10-20 devices (81% fixed), 3-6 trees, 30-50 events, and 10-30 months. Predominant global values of TF, CI, and SF are 70-80% (median = 73%), 20%-30% (median = 23.9%), and <1.0% (median = 1.87%), respectively. Global models of CI and TF were responsive to T, LAI, and D (respectively, R2adj of 0.196** and 0.206**). Temperate forests mirrored the global model (R2adj of 0.274** and 0.31**, respectively). The Subtropical CI model was fitted based on P and DBH (R2adj = 0.245*), and the TF model was based on E, D, and LAI (R2adj = 0.532**); the Mediterranean CI model was based on T, Basal, and LAI (R2adj = 0.45*), while TF was based on P, Basal, and LAI (R2adj = 0.671**). The Tropical CI model was based on T and H (R2adj = 0.396*), and the TF model, LAI, and P (R2adj = 0.35*). This meta-analysis underscores the importance of comprehending the hydrological processes in forested areas as they are pivotal in mitigating climate change impacts.

Toxic side-effects of diaspirin cross-linked human hemoglobin are attenuated by the apohemoglobin-haptoglobin complex.

Alpha-alpha diaspirin-crosslinked human hemoglobin (DCLHb or ααHb) was a promising early generation red blood cell (RBC) substitute. The DCLHb was developed through a collaborative effort between the United States Army and Baxter Healthcare. The core design feature underlying its development was chemical stabilization of the tetrameric structure of hemoglobin (Hb) to prevent Hb intravascular dimerization and extravasation. DCLHb was developed to resuscitate warfighters on the battlefield, who suffered from life-threatening blood loss. However, extensive research revealed toxic side effects associated with the use of DCLHb that contributed to high mortality rates in clinical trials. This study explores whether scavenging Hb and heme via the apohemoglobin-haptoglobin (apoHb-Hp) complex can reduce DCLHb associated toxicity. Awake Golden Syrian hamsters were equipped with a window chamber model to characterize the microcirculation. Each group was first infused with either Lactated Ringer's or apoHb-Hp followed by a hypovolemic infusion of 10% of the animal's blood volume of DCLHb. Our results indicated that animals pretreated with apoHb-Hb exhibited improved microhemodynamics vs the group pretreated with Lactated Ringer's. While systemic acute inflammation was observed regardless of the treatment group, apoHb-Hp pretreatment lessened those effects with a marked reduction in IL-6 levels in the heart and kidneys compared to the control group. Taken together, this study demonstrated that utilizing a Hb and heme scavenger protein complex significantly reduces the microvasculature effects of ααHb, paving the way for improved HBOC formulations. Future apoHb-Hp dose optimization studies may identify a dose that can completely neutralize DCLHb toxicity.

Alzheimer's disease heterogeneity revealed by neuroanatomical normative modeling.

INTRODUCTION: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy. METHODS: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD (n = 86). Regional cortical thickness was compared to a healthy reference cohort (n = 33,072) and the number of outlying regions was summed (total outlier count) and mapped at individual- and group-levels. RESULTS: The superior temporal sulcus contained the highest proportion of outliers (60%). Elsewhere, overlap between patient atrophy patterns was low. Mean total outlier count was higher in patients who were non-amnestic, at more advanced disease stages, and without depressive symptoms. Amyloid burden was negatively associated with outlier count. DISCUSSION: Brain atrophy in AD is highly heterogeneous and neuroanatomical normative modeling can be used to explore anatomo-clinical correlations in individual patients.

Helical coil design with controlled dispersion for bunching enhancement of protons generated by the target normal sheath acceleration.

The quality of the proton beam produced by target normal sheath acceleration (TNSA) with high-power lasers can be significantly improved with the use of helical coils. While they showed promising results in terms of focusing, their performances in terms of the of cut-off energy and bunching stay limited due to the dispersive nature of helical coils. A new scheme of helical coil with a tube surrounding the helix is introduced, and the first numerical simulations and an analytical model show a possibility of a drastic reduction of the current pulse dispersion for the parameters of high-power-laser facilities. The helical coils with tube strongly increase bunching, creating two collimated narrow-band proton beams from a broad and divergent TNSA distribution. The analytical model provides scaling of proton parameters as a function of laser facility features.

Occupational exposure to particulate matter and staff sickness absence on the London underground.

The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m3), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM2.5. They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM2.5. Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose-response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10-1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM2.5 exposure and may have wider implications for subway workers, contributing to safer working environments.

A Measure of Synergy Based on Union Information.

The partial information decomposition (PID) framework is concerned with decomposing the information that a set of (two or more) random variables (the sources) has about another variable (the target) into three types of information: unique, redundant, and synergistic. Classical information theory alone does not provide a unique way to decompose information in this manner and additional assumptions have to be made. One often overlooked way to achieve this decomposition is using a so-called measure of union information-which quantifies the information that is present in at least one of the sources-from which a synergy measure stems. In this paper, we introduce a new measure of union information based on adopting a communication channel perspective, compare it with existing measures, and study some of its properties. We also include a comprehensive critical review of characterizations of union information and synergy measures that have been proposed in the literature.

Urology Residency Applicant Selection: Program Directors' New Criteria.

OBJECTIVE: To evaluate the impact of the recent changes to the urology residency application process on the criteria utilized by residency program directors (PDs) for interview invitations and their perspectives concerning these changes. METHODS: One hundred thirty-seven urology residency PDs were invited to participate in an anonymous survey to explore interview selection criteria and the impact of the increase in preference signals (PS) per applicant. RESULTS: Fifty-eight PDs (42.8%) completed the survey. The highest-ranked criteria were letters of recommendation (LoR) and successful sub-internship (sub-I) at the PD's institution, without statistically significant differences between these 2. Gender, ethnicity, and medical school prestige were the lowest rated criteria, without significant differences between these 3. Compared to before the increase in the number of PS per applicant, 80.7% of PDs reported that not receiving a PS from an applicant this cycle would more negatively impact the chances of offering an interview to that applicant. Moreover, 12.2% stated they would not interview any applicants who did not send a PS. Finally, 62.1% of PDs believed recent changes worsened the process. CONCLUSION: Recent changes impacted PDs applicant evaluation, with the highest ranked criteria being LoRs and sub-I. Paradoxically, the increase in the number of PS per applicant has increased their importance as applicants are much less likely to receive interview offers from programs they have not signaled. Lastly, most PDs believe changes have worsened the evaluation process.

Surgical treatment of patients with chronic rupture of the pectoralis major muscle tendon. Prospective comparative study with 2 years of follow-up.

To compare outcomes between autologous fascia lata and autologous hamstring grafts for chronic pectoralis major muscle (PMM) rupture repair, and perform histological, and imaging analyses. Forty male patients with chronic PMM ruptures (time since injury ranging from >3 months to 5 years) and a mean age of 37.3 years (SD = 9.7 years) were evaluated. One group (20 patients) received an autologous semitendinosus graft, and another group (20 patients) received an autologous fascia lata graft for PMM reconstruction. These patients with fascia lata grafts by Bak 2criterium 60% of the patients presented excellent results, 20% presented good results, 15% presented fair results, and 5% presented poor results. In the hamstring group 65% of the patients presented excellent results, 30% presented good results, and 5% presented fair results. In this comparative study, no difference was observed regarding the functional result, image, and histology between groups.