Photomolecular effect: Visible light interaction with air-water interface.

Although water is almost transparent to visible light, we demonstrate that the air-water interface interacts strongly with visible light via what we hypothesize as the photomolecular effect. In this effect, transverse-magnetic polarized photons cleave off water clusters from the air-water interface. We use 14 different experiments to demonstrate the existence of this effect and its dependence on the wavelength, incident angle, and polarization of visible light. We further demonstrate that visible light heats up thin fogs, suggesting that this process can impact weather, climate, and the earth's water cycle and that it provides a mechanism to resolve the long-standing puzzle of larger measured clouds absorption to solar radiation than theory could predict based on bulk water optical constants. Our study suggests that the photomolecular effect should happen widely in nature, from clouds to fogs, ocean to soil surfaces, and plant transpiration and can also lead to applications in energy and clean water.

A primer on the use of machine learning to distil knowledge from data in biological psychiatry.

Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data. This article provides an accessible and critical review of machine learning for a biomedically informed audience, as well as its applications in psychiatry. The review covers definitions and expositions of commonly used machine learning methods, and historical trends of their use in psychiatry. We also provide a set of standards, namely Guidelines for REporting Machine Learning Investigations in Neuropsychiatry (GREMLIN), for designing and reporting studies that use machine learning as a primary data-analysis approach. Lastly, we propose the establishment of the Machine Learning in Psychiatry (MLPsych) Consortium, enumerate its objectives, and identify areas of opportunity for future applications of machine learning in biological psychiatry. This review serves as a cautiously optimistic primer on machine learning for those on the precipice as they prepare to dive into the field, either as methodological practitioners or well-informed consumers.

Predicting childhood and adolescent attention-deficit/hyperactivity disorder onset: a nationwide deep learning approach.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder with a high degree of psychiatric and physical comorbidity, which complicates its diagnosis in childhood and adolescence. We analyzed registry data from 238,696 persons born and living in Sweden between 1995 and 1999. Several machine learning techniques were used to assess the ability of registry data to inform the diagnosis of ADHD in childhood and adolescence: logistic regression, random Forest, gradient boosting, XGBoost, penalized logistic regression, deep neural network (DNN), and ensemble models. The best fitting model was the DNN, achieving an area under the receiver operating characteristic curve of 0.75, 95% CI (0.74-0.76) and balanced accuracy of 0.69. At the 0.45 probability threshold, sensitivity was 71.66% and specificity was 65.0%. There was an overall agreement in the feature importance among all models (τ > .5). The top 5 features contributing to classification were having a parent with criminal convictions, male sex, having a relative with ADHD, number of academic subjects failed, and speech/learning disabilities. A DNN model predicting childhood and adolescent ADHD trained exclusively on Swedish register data achieved good discrimination. If replicated and validated in an external sample, and proven to be cost-effective, this model could be used to alert clinicians to individuals who ought to be screened for ADHD and to aid clinicians' decision-making with the goal of decreasing misdiagnoses. Further research is needed to validate results in different populations and to incorporate new predictors.

Comparison of intra-operative outcomes following internal fixation with trochanteric stabilisation plate or intramedullary nail in intertrochanteric fractures.

PURPOSE: Intertrochanteric fractures can be classified as stable (AO-OTA 31-A1) or unstable (AO-OTA 31-A2/3). For A3 fractures there is no recommended treatment, often fixed with either an intramedullary nail (IMN) or a dynamic hip screw and trochanteric stabilisation plate (DHS/TSP). This study retrospectively reviews peri-operative outcomes of patients treated with either fixator. METHODS: Pre-operative demographics, operative information and patient outcome data from 213 patients who suffered intertrochanteric fractures and were treated with either DHS/TSP or IMN at a major trauma centre from 01/2015 to 01/2022 was collected. Unpaired T tests were performed to assess levels of significance between peri-operative outcomes. RESULTS: The mean age for DHS/TSP-treated patients was 2.63 years greater than IMN-treated (P = 0.039). There were no other significant differences in pre-operative characteristics. We found a significantly shorter mean operative time in the DHS/TSP group (88.05 min, 95% CI: 82.1-94.0) compared to IMN counterparts (100.8 min, 95% CI: 92.7-109.0, P = 0.012), but no statistically significant difference in length of hospital stay or patient mortality, blood transfusion, re-operation or complication rates. When A3 fractures were analysed, a statistically significant greater proportion of IMN patients required blood transfusions (DHS/TSP: 35.90%, IMN: 65.00%, P = 0.0093). All other factors were found to have no significant differences. CONCLUSION: This study provides evidence to support the national guidelines regarding A1 fractures and suggests that DHS/TSP is a valid alternative to the IMN in A3 intertrochanteric fractures, with reduced blood loss. With the flexibility to add the TSP intraoperatively to prevent femoral head medialisation, and cheaper implant costs, the DHS/TSP may become the preferred method of internal fixation.

Developing an Integrated Longitudinal Dataset for Patient-Centered Outcome Measures in Cost-Related Medication Nonadherence.

BACKGROUND: Cost-related medication nonadherence (CRN) is an important patient-centered outcome measure. Longitudinal follow-up of CRN is rare. OBJECTIVE: We propose to develop a novel integrated dataset to study CRN longitudinally. RESEARCH DESIGN: A dataset of 2000 Medicare beneficiaries at high risk of hospitalization surveyed quarterly on CRN and followed up individually for 8 quarters between 2013 and 2018 was linked to Medicare files. A metric of CRN categorizing persistent, intermittent, and transient CRN during the 8 quarters was developed. An ordered logit model and a logit model were developed to assess the factors influencing CRN overall and persistent CRN, respectively. RESULTS: A total of 1761 patients were included in the analysis, among whom 869 (49.3%) reported CRN at least once in the 8-quarter study period, 178 (10%) reported persistent CRN, 395 (22.4%) reported intermittent CRN, and 296 (16.8%) reported transient CRN. The conditional effect in the logit model for persistent CRN revealed that baseline dual eligibility was negatively associated (adjusted odds ratio = 0.45, P < 0.01) and depression positively associated (adjusted odds ratio = 1.55, P = 0.01) with persistent CRN. The marginal analysis in the ordered logit model revealed a clear pattern of higher probabilities of persistent and intermittent CRN at younger ages while transient CRN was flat. Among the 252 subjects who were deceased, 31 (12.3%) reported persistent CRN, compared with 147 (9.74%) who were alive (P = 0.21 by χ2 test). CONCLUSIONS: A significant number of patients reported persistent CRN, including those who were at the end of life. Research is critically needed to understand behavioral patterns among the younger Medicare population.

Daily cannabis use may cause cannabis-induced hyperalgesia.

BACKGROUND AND OBJECTIVES: Public opinion about cannabis as a medical treatment is generally favorable. As many as 35% of primary care patients report medical use of cannabis, most commonly for pain treatment. We designed a way to test whether cannabis helps chronic pain. METHODS: A retrospective cohort study was conducted to explore whether daily long-term cannabis use was associated with increased pain sensitivity using the cold pressor test (CPT) to measure pain tolerance. Patients who used cannabis every day were compared to patients who inhaled tobacco and control patients who never used tobacco or cannabis. The effect of cannabis use on CPT was assessed using a generalized linear model. RESULTS: Patients using cannabis daily had a median CPT of 46 s, similar to those who did not use cannabis but who inhaled tobacco (median CPT 45 s). Patients who used both cannabis and tobacco had the lowest CPT (median 26 s). The control group had a median CPT of 105 s. Cannabis use was associated with a significantly decreased pain tolerance (χ²(1) = 8.0, p = .004). The effect of tobacco on CPT was only marginally significant (χ²(1) = 3.8, p = .052). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This suggests a phenomenon similar to opioid-induced hyperalgesia; a drug that reduces pain short term, induces pain long term-opponent process. Daily cannabis use may make chronic pain worse over time by reducing pain tolerance. In terms of risk/benefit, daily cannabis users risk addiction without any long-term benefit for chronic pain.

The impact of extended reality on surgery: a scoping review.

PURPOSE: Extended reality (XR) is defined as a spectrum of technologies that range from purely virtual environments to enhanced real-world environments. In the past two decades, XR-assisted surgery has seen an increase in its use and also in research and development. This scoping review aims to map out the historical trends in these technologies and their future prospects, with an emphasis on the reported outcomes and ethical considerations on the use of these technologies. METHODS: A systematic search of PubMed, Scopus, and Embase for literature related to XR-assisted surgery and telesurgery was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Primary studies, peer-reviewed articles that described procedures performed by surgeons on human subjects and cadavers, as well as studies describing general surgical education, were included. Non-surgical procedures, bedside procedures, veterinary procedures, procedures performed by medical students, and review articles were excluded. Studies were classified into the following categories: impact on surgery (pre-operative planning and intra-operative navigation/guidance), impact on the patient (pain and anxiety), and impact on the surgeon (surgical training and surgeon confidence). RESULTS: One hundred and sixty-eight studies were included for analysis. Thirty-one studies investigated the use of XR for pre-operative planning concluded that virtual reality (VR) enhanced the surgeon's spatial awareness of important anatomical landmarks. This leads to shorter operating sessions and decreases surgical insult. Forty-nine studies explored the use of XR for intra-operative planning. They noted that augmented reality (AR) headsets highlight key landmarks, as well as important structures to avoid, which lowers the chance of accidental surgical trauma. Eleven studies investigated patients' pain and noted that VR is able to generate a meditative state. This is beneficial for patients, as it reduces the need for analgesics. Ten studies commented on patient anxiety, suggesting that VR is unsuccessful at altering patients' physiological parameters such as mean arterial blood pressure or cortisol levels. Sixty studies investigated surgical training whilst seven studies suggested that the use of XR-assisted technology increased surgeon confidence. CONCLUSION: The growth of XR-assisted surgery is driven by advances in hardware and software. Whilst augmented virtuality and mixed reality are underexplored, the use of VR is growing especially in the fields of surgical training and pre-operative planning. Real-time intra-operative guidance is key for surgical precision, which is being supplemented with AR technology. XR-assisted surgery is likely to undertake a greater role in the near future, given the effect of COVID-19 limiting physical presence and the increasing complexity of surgical procedures.

Predictors for infection severity for open tibial fractures: major trauma centre perspective.

INTRODUCTION: Open diaphyseal tibial fractures are the most common long-bone fractures and require a rapid approach to prevent devastating complications. Current literature reports the outcomes of open tibial fractures. However, there is no robust, up-to-date research on the predictive indicators of infection severity in a large open tibial fracture patient cohort. This study investigated the predictive factors of superficial infections and osteomyelitis in open tibial fractures. MATERIALS AND METHODS: A retrospective analysis of the tibial fracture database was carried out from 2014 to 2020. Criteria for inclusion was any tibial fracture including tibial plateau, shaft, pilon or ankle, with an open wound at the fracture site. Exclusion criteria included patients with a follow-up period of less than 12 months and who are deceased. A total of 235 patients were included in our study, of which 154 (65.6%), 42 (17.9%), and 39 (16.6%) developed no infection, superficial infection, or osteomyelitis, respectively. Patient demographics, injury characteristics, fracture characteristics, infection status and management details were collected for all patients. RESULTS: On multivariate modelling, patients with BMI > 30 (OR = 2.078, 95%CI [1.145-6.317], p = 0.025), Gustilo-Anderson (GA) type III (OR = 6.120, 95%CI [1.995-18.767], p = 0.001), longer time to soft tissue cover (p = 0.006) were more likely to develop a superficial infection, and patients with wound contamination (OR = 3.152, 95%CI [1.079-9.207], p = 0.036), GA-3 (OR = 3.387,95%CI [1.103-10.405], p = 0.026), longer to soft tissue cover (p = 0.007) were more likely to develop osteomyelitis. Univariate analysis also determined that risk factors for superficial infection were: BMI > 35 (OR = 6.107, 95%CI [2.283-16.332], p = 0.003) and wound contamination (OR = 2.249, 95%CI [1.015-5.135], p = 0.047); whilst currently smoking (OR = 2.298, 95%CI [1.087-4.856], p = 0.025), polytrauma (OR = 3.212, 95%CI [1.556-6.629], p = 0.001), longer time to definitive fixation (p = 0.023) were for osteomyelitis. However, none of these reached significance in multivariate analysis. CONCLUSION: Higher GA classification is a significant risk factor for developing superficial infection and osteomyelitis, with a stronger association with osteomyelitis, especially GA 3C fractures. Predictors for superficial infection included BMI and time to soft tissue closure. Time to definitive fixation, time to soft tissue closure, and wound contamination were associated with osteomyelitis.

Ankle fusion with tibiotalocalcaneal retrograde nail for fragility ankle fractures: outcomes at a major trauma centre.

PURPOSE: Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, and patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with retrograde ankle fusion nails. METHODS: A retrospective observational study was performed on patients who underwent intramedullary nailing with a tibiotalocalcaneal nail. Twenty patients met the inclusion criteria of being over sixty and having multiple co-morbidities. Patient demographics, AO/OTA fracture classification, intra-operative and post-operative complications, time to mobilisation and union, AOFAS and Olerud-Molander scores, and patient mobility were recorded. RESULTS: There were seven males and thirteen females, with a mean age of 77.82 years old, five of whom are type 2 diabetics. Thirteen patients returned to their pre-operative mobility state, and the average Charlson Co-morbidity Index (CCI) was 5.05. Patients with a low CCI are more likely to return to pre-operative mobility status (p = 0.16; OR = 4.00). All patients achieved radiographical union, taking on average between 92.5 days and 144.6 days. The mean post-operative AOFAS and Olerud-Molander scores were 53.0 and 50.9, respectively. There were four cases of superficial infection, four cases of broken or loose distal locking screws. There were no deep infections, periprosthetic fractures, nail breakages, or non-unions. CONCLUSION: Tibiotalocalcaneal nailing is an effective and safe option for managing unstable ankle fractures in the elderly. This technique leads to lower complication rates and earlier mobilisation than traditional fixation methods.

A retrospective analysis of the definitive management of open talus fractures at a major trauma centre, comparing ORIF to FUSION: cohort study and audit of BOAST 4 guidelines.

PURPOSE: Open talus fractures are notoriously difficult to manage, and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, and thus, definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons are early debridement, orthoplastic wound care, anatomic reduction and definitive fixation whenever possible. However, there is much debate over whether the talus should be preserved or removed after open talus fracture/dislocation and proceeded to tibiocalcaneal fusion. METHODS: A review of electronic hospital records for open talus fractures from 2014 to 2021 returned fourteen patients with fifteen open talus fractures. Seven cases were initially managed with ORIF, and five cases were definitively managed with FUSION, while the others were managed with alternative methods. We collected patient's age, gender, surgical complications, surgical risk factors and post-treatment functional ability and pain and compliance with BOAST guidelines. The average follow-up of the cohort was 4 years and one month. EQ-5D-5L and FAAM-ADL/Sports score was used as a patient reported outcome measure. Data were analysed using the software PRISM. RESULTS: Comparison between FUSION and ORIF groups showed no statistically significant difference in EQ-5D-5L score (P = 0.13), FAAM-ADL (P = 0.20), FAAM-Sport (P = 0.34), infection rate (P = 0.55), surgical times (P = 0.91) and time to weight bearing (P = 0.39), despite a higher proportion of polytrauma and Hawkins III and IV fractures in the FUSION group. CONCLUSION: FUSION is typically used as second line to ORIF or failed ORIF. However, there is a lack of studies that directly compared outcome in open talus fracture patients definitively managed with FUSION or ORIF. Our results demonstrate for the first time that FUSION may not be inferior to ORIF in terms of patient functional outcome, infection rate and quality of life, in the management of patients with open talus fracture patients. Of note, as open talus fractures have increased risks of complications such as osteonecrosis and non-union, FUSION should be considered as a viable option to mitigate these potential complications in these patients.

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.

COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Forty-three articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%). Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.

Significance of family history in understanding and subtyping trichotillomania.

BACKGROUND AND AIMS: The existence of subtypes of trichotillomania (TTM) have long been hypothesized, and recent studies have further elucidated characteristic subtypes of TTM and possible ramifications of subtyping for treatment. In clinical applications of subtyping for treatment of TTM, family history (FH) of psychiatric disorders in patients may serve as a tool to differentiate disorder presentations and inform care. We compared prevalence of psychiatric illnesses in first-degree relatives of participants with TTM and healthy controls, respectively, in a large sample, and examined associations between those psychiatric disorders that were significantly different in the FH between groups and measures of disability, severity, and neuropsychological constructs. METHODS: We compared FHs of 152 participants (mean age = 29.9) with TTM and 71 healthy controls (mean age = 29.6), utilizing chi-squared tests to determine which psychiatric illnesses were more prevalent in FHs of participants with TTM. We then used two-tailed t-tests to compare TTM participants with those more prevalent FHs to participants without those FHs on measures of disorder severity, disability, and neuropsychological constructs. FINDINGS: Obsessive-compulsive disorder (OCD), TTM, skin picking disorder (SPD), and major depressive disorder (MDD) were significantly more frequent in first-degree relatives (p < 0.0033) of TTM participants than those of healthy controls. TTM participants with a FH of OCD scored significantly higher on measures of impulsivity and lower on measures of distress tolerance. Those with FH of TTM, SPD, and MDD did not differ significantly across measured variables. CONCLUSION: OCD, TTM, SPD, and MDD are more prevalent in the FHs of people with TTM, as compared to healthy controls. TTM participants with a family history of OCD may be more likely to demonstrate decreased distress tolerance and increased impulsivity. In all, as understanding of TTM subtypes develops, the FH may prove a useful tool in delineating subtypes and informing care.

Lumbar decompression surgery for cauda equina syndrome - comparison of complication rates between daytime and overnight operating.

PURPOSE: To investigate the incidence of complications from lumbar decompression ± discectomy surgery for cauda equina syndrome (CES), assessing whether time of day is associated with a change in the incidence of complications. METHODS: Electronic clinical and operative notes for all lumbar decompression operations undertaken at our institution for CES over a 2-year time period were retrospectively reviewed. "Overnight" surgery was defined as any surgery occurring between 18:00 and 08:00 on any day. Clinicopathological characteristics, surgical technique, and peri/post-operative complications were recorded. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals. RESULTS: A total of 81 lumbar decompression operations were performed in the 2-year period and analysed. A total of 29 (36%) operations occurred overnight. Complete CES (CESR) was seen in 13 cases (16%) in total, 7 of whom underwent surgery during the day. Exactly 27 complications occurred in 24 (30%) patients. The most frequently occurring complication was a dural tear (n = 21, 26%), followed by post-operative haematoma, infection, and residual disc. Complication rates in the CESR cohort (54%) were significantly greater than in the CES incomplete (CESI) cohort (25%) (p = 0.04). On multivariable analysis, overnight surgery was independently associated with a significantly increased complication rate (OR 2.83, CI 1.02-7.89). CONCLUSIONS: Lumbar decompressions performed overnight for CES were more than twice as likely to suffer a complication, in comparison to those performed within daytime hours. Our study suggests that out-of-hours operating, particularly at night, must be clinically justified and should not be influenced by day-time operating capacity.

Management of post-traumatic femoral defects with a monorail external fixator over an intramedullary nail.

PURPOSE: The management of limb-length discrepancy secondary to traumatic femoral bone loss poses a unique challenge for surgeons. The Ilizarov technique is popular, but is associated with long external fixator time and many complications. This retrospective study assessed outcomes of post-traumatic femoral defects managed by monorail external fixation over an intramedullary nail. METHODS: Eight patients were included from October 2015 to May 2019 with post-traumatic femoral defects that underwent treatment with monorail fixator-assisted intramedullary nailing. Primary outcome was time to bone union and bone results according to ASAMI classification. Secondary outcomes were lengthening index, consolidation time and index, external fixator index (EFI), time to partial weight bearing(PWB) and full weight bearing (FWB), and complications. Patient reported outcome measures including EQ-5D-5L, SF-36, Oxford knee scores (OKS), and Oxford hip scores (OHS) were recorded after recovery. RESULTS: Mean follow-up time was 227 weeks. Average bone defect size was 9.69 cm. Average consolidation time and index were 11.35 months and 1.24 months/cm, respectively. Mean lengthening and external fixator index were 20.2 days/cm and 23.88 days/cm, respectively. On average, patients achieved FWB and bone union 56.25 weeks and 68.83 weeks after bone transport initiation, respectively. Two patients had docking site non-union, five patients had pin site infections, and two patients had osteomyelitis. EQ-5D-5L and EQ-VAS scores were compared to UK population norms (p = 0.104, p = 0.238, respectively). Average OKS was 32.17 and OHS was 34.00. CONCLUSION: Monorail external fixation over an intramedullary nail is an effective option for post-traumatic femoral defects, reducing external fixator time and returning patients' quality of life to a level comparable with the normal population.

Thermally regenerative electrochemically cycled flow batteries with pH neutral electrolytes for harvesting low-grade heat.

Harvesting waste heat with temperatures lower than 100 °C can improve the system efficiency and reduce greenhouse gas emissions, yet it has been a longstanding and challenging task. Electrochemical methods for harvesting low-grade heat have aroused research interest in recent years due to the relatively high effective temperature coefficient of the electrolytes (>1 mV K-1) compared with the thermopower of traditional thermoelectric devices. Compared with other electrochemical devices such as the temperature-variation based thermally regenerative electrochemical cycle and temperature-difference based thermogalvanic cells, the thermally regenerative electrochemically cycled flow battery (TREC-FB) has the advantages of providing a continuous power output, decoupling the heat source and heat sink, and recuperating heat, and compatible with stacking for scaling up. However, the TREC-FB suffers from the issue of stable operation due to the challenge of pH matching between catholyte and anolyte solutions with desirable temperature coefficients. In this work, we demonstrate a pH-neutral TREC-FB based on KI/KI3 and K3Fe(CN)6/K4Fe(CN)6 as the catholyte and anolyte, respectively, with a cell temperature coefficient of 1.9 mV K-1 and a power density of 9 µW cm-2. This work also presents a comprehensive model with a coupled analysis of mass transfer and reaction kinetics in a porous electrode that can accurately capture the flow rate dependence of the power density and energy conversion efficiency. We estimate that the efficiency of the pH-neutral TREC-FB can reach nearly 9% of the Carnot efficiency at the maximum power output with a temperature difference of 37 K. Via analysis, we identify that the mass transfer overpotential inside the porous electrode and the resistance of the ion exchange membrane are the two major factors limiting the efficiency and power density, pointing to directions for future improvements.

Thromboprophylaxis for patients with newly diagnosed vs. recurrent cancers: a post-hoc analysis of the avert trial.

Venous thromboembolic disease (VTE) is a common complication among patients with cancer. Data reporting risk of VTE among patients receiving chemotherapy for recurrent cancer compared to those with newly diagnosed tumors is scarce. Furthermore, it is unclear if thromboprophylaxis is beneficial and safe in these specific patient populations. Post-hoc analysis of the AVERT trial which was a randomized, placebo-controlled, double-blind trial comparing apixaban therapy to placebo for VTE prophylaxis among cancer patients who were intermediate-to-high risk for VTE and who were initiating chemotherapy. The HRs for recurrent VTE and major bleeding episodes in patients with newly diagnosed and recurrent cancers were calculated using a Cox regression model controlling for age, gender, and center. Of the 563 included patients 469 and 93 patients had newly diagnosed and recurrent cancers, respectively. Patients with recurrent cancer have a higher risk of VTE (Hazard ratio (HR): 1.53 (95% CI 1.0 to 2.33; p = 0.047) and major bleeding episodes (HR 2.89 (95% CI 1.52 to 5.49; p = 0.001) compared to those with newly diagnosed cancer. In patients with newly diagnosed cancers, the use of apixaban was associated with a significantly lower risk of VTE (HR 0.45; 95% CI 0.27-0.76; p = 0.002) and a higher rate of major bleeding (HR 2.10; 95% CI 1.09-4.08; p = 0.028). In patients with recurrent cancer, apixaban was associated with a significant lower rate of VTE (HR 0.26; 95% CI 0.13-0.53; p < 0.001) without an associated significantly increased risk of major bleeding (HR 1.82; 95% CI 0.36-9.15; p = 0.466). Patients with recurrent cancer seem to be at higher risk of recurrent VTE and major bleeding complications compared to those with newly diagnosed tumors. Apixaban appears to be safe and effective in these patient populations.

Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke.

Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. These LMO3-iPS-NPCs can be activated by either photostimulation using light or by the luciferase substrate coelenterazine (CTZ). In vitro stimulations of LMO3-iPS-NPCs increased expression of synapsin-1, postsynaptic density 95, brain derived neurotrophic factor (BDNF), and stromal cell-derived factor 1 and promoted neurite outgrowth. After transplantation into the ischemic cortex of mice, LMO3-iPS-NPCs differentiated into mature neurons. Synapse formation between implanted and host neurons was identified using immunogold electron microscopy and patch-clamp recordings. Stimulation of transplanted cells with daily intranasal administration of CTZ enhanced axonal myelination, synaptic transmission, improved thalamocortical connectivity, and functional recovery. Patch-clamp and multielectrode array recordings in brain slices showed that CTZ or light stimulation facilitated synaptic transmission and induced neuroplasticity mimicking the LTP of EPSPs. Stroke mice received the combined LMO3-iPS-NPC/CTZ treatment, but not cell or CTZ alone, showed enhanced neural network connections in the peri-infarct region, promoted optimal functional recoveries after stroke in male and female, young and aged mice. Thus, excitation of transplanted cells via the noninvasive optochemogenetics treatment provides a novel integrative cell therapy with comprehensive regenerative benefits after stroke.SIGNIFICANCE STATEMENT Neural network reconnection is critical for repairing damaged brain. Strategies that promote this repair are expected to improve functional outcomes. This study pioneers the generation and application of an optochemogenetics approach in stem cell transplantation therapy after stroke for optimal neural repair and functional recovery. Using induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) expressing the novel optochemogenetic probe luminopsin (LMO3), and intranasally delivered luciferase substrate coelenterazine, we show enhanced regenerative properties of LMO3-iPS-NPCs in vitro and after transplantation into the ischemic brain of different genders and ages. The noninvasive repeated coelenterazine stimulation of transplanted cells is feasible for clinical applications. The synergetic effects of the combinatorial cell therapy may have significant impacts on regenerative approach for treatments of CNS injuries.

Predicting suicide attempt or suicide death following a visit to psychiatric specialty care: A machine learning study using Swedish national registry data.

BACKGROUND: Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the Swedish national registry data for prediction of suicidal behavior. METHODS AND FINDINGS: The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval [CI] = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown. CONCLUSIONS: By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation.

Improved trafficking and expression of luminopsins for more efficient optical and pharmacological control of neuronal activity.

Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provide control of neuronal activity, allowing for less cumbersome and less invasive optogenetic manipulation. It was previously shown that both an external light source and the luciferase substrate, coelenterazine (CTZ), could modulate activity of LMO-expressing neurons, although the magnitudes of the photoresponses remained subpar. In this study, we created an enhanced iteration of the excitatory luminopsin LMO3, termed eLMO3, that has improved membrane targeting due to the insertion of a Golgi trafficking signal sequence. In cortical neurons in culture, the expression of eLMO3 resulted in significant reductions in the formation of intracellular aggregates, as well as in a significant increase in total photocurrents. Furthermore, we corroborated the findings with injections of adeno-associated viral vectors into the deep layers of the somatosensory cortex (the barrel cortex) of male mice. We observed greatly reduced numbers of intracellular puncta in eLMO3-expressing cortical neurons compared to those expressing the original LMO3. Finally, we quantified CTZ-driven behavior, namely whisker-touching behavior, in male mice with LMO3 expression in the barrel cortex. After CTZ administration, mice with eLMO3 displayed significantly longer whisker responses than mice with LMO3. In summary, we have engineered the superior LMO by resolving membrane trafficking defects, and we demonstrated improved membrane targeting, greater photocurrents, and greater functional responses to stimulate with CTZ.