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Typical assessments of balance impairment are subjective or require data from cumbersome and expensive force platforms. Researchers have utilized lower back (sacrum) accelerometers to enable more accessible, objective measurement of postural sway for use in balance assessment. However, new sensor patches are broadly being deployed on the chest for cardiac monitoring, opening a need to determine if measurements from these devices can similarly inform balance assessment. Our aim in this work is to validate postural sway measurements from a chest accelerometer. To establish concurrent validity, we considered data from 16 persons with multiple sclerosis (PwMS) asked to stand on a force platform while also wearing sensor patches on the sacrum and chest. We found five (five) of 15 postural sway features derived from chest (sacrum) were significantly correlated with force platform-derived features, which is in line with prior sacrum-derived findings. Clinical significance was established using a sample of 39 PwMS who performed eyes-open, eyes-closed, and tandem standing tasks. This cohort was stratified by fall status and completed several patient-reported measures (PRM) of balance and mobility impairment. We also compared sway features derived from a single 30-second period to those derived from a one-minute period with a sliding window to create subject-specific distributions of each postural sway feature (SSD method). We find traditional computation of sway features from the chest is sensitive to changes in PRMs and task differences. Distribution characteristics from the SSD method establish additional relationships with PRMs, detect differences in more tasks, and distinguish between fall status groups. Overall, the chest was found to be a valid location to monitor postural sway and we recommend utilizing the SSD method over single-observation analyses.

Impairment in persons with multiple sclerosis (PwMS) can often be attributed to symptoms of motor instability and fatigue. Symptom monitoring and queued interventions often target these symptoms. Clinical metrics are currently limited to objective physician assessments or subjective patient reported measures. Recent research has turned to wearables for improving the objectivity and temporal resolution of assessment. Our group has previously observed wearable assessment of supervised and unsupervised standing transitions to be predictive of fall-risk in PwMS. Here we extend the application of standing transition quantification to longitudinal home monitoring of symptoms. Subjects (N=23) with varying degrees of MS impairment were recruited and monitored with accelerometry for a total of ~6 weeks each. These data were processed using a deep learning activity classifier to isolate periods of standing transition from which descriptive features were extracted for analysis. Participants completed daily and biweekly assessments describing their symptoms. From these data, Canonical Correlation Analysis was used to derive digital phenotypes of MS instability and fatigue. We find these phenotypes capable of distinguishing fallers from non-fallers, and further that they demonstrate a capacity to characterize symptoms at both daily and sub-daily resolutions. These results represent promising support for future applications of wearables, which may soon augment or replace current metrics in longitudinal monitoring of PwMS.

Background There is limited information on the frequency of complications among older adults after oncological thoracic surgery in the modern era. We hypothesized that morbidity and mortality in older adults with lung cancer undergoing lobectomy is low and different than that of younger patients undergoing thoracic surgery. Methods All patients undergoing lobectomy at a large volume academic center between May 2016 and May 2019 were included. Patients were prospectively monitored to grade postoperative morbidity by organ system, based on the Clavien-Dindo classification. Patients were divided into two groups: Group 1 included patients 65–91 years of age, and Group 2 included those Results Of 680 lobectomies in 673 patients, 414(61%) were older than 65 years of age (group 1). Median age at surgery was 68 years (20–91). Median hospital stay was 4 days (1–38) and longer in older adults. Older adults experienced higher rates of grade II and IV complications, mostly driven by an increased incidence of delirium, atrial fibrillation, prolonged air leak, respiratory failure and urinary retention. In this modern cohort, there was only 1 stroke (0.1%), and delirium was reduced to 7%. Patients undergoing minimally invasive (MI) surgery had a lower rate of Grade IV life-threatening complications. Older adults were more likely to be discharged to a rehabilitation facility, however this difference also disappeared with MI surgical procedures. Conclusions Current morbidity of older adults undergoing lobectomy for cancer is low and is different than that of younger patients. Thoracotomy may be associated with postoperative complications in these patients. Our findings suggest the need to consider MI approaches and broad-based, geriatric-focused perioperative management of older adults undergoing lobectomy.

Objective The purpose of this study was to determine the incidence of venous thromboembolism and utility of a routine surveillance program in patients undergoing surgery for mesothelioma. Methods Patients undergoing pleurectomy from May 2016 to August 2018 were included. A standardized surveillance program to look for venous thromboembolism in this group included noninvasive studies every 7 days postoperatively or earlier if symptomatic. All patients received external pneumatic compression sleeves in addition to prophylactic heparin. If deep vein thrombosis or pulmonary embolus was discovered, heparin drip was initiated until conversion to therapeutic anticoagulation. Results A total of 100 patients underwent pleurectomy for mesothelioma. Seven patients were found to have preoperative deep vein thrombosis, and as such only 93 patients were included for analysis. The median age of patients at surgery was 71 years (30-85 years). During the study, 30 patients (32%) developed evidence of thrombosis; 20 patients (22%) developed only deep vein thrombosis without embolism, 3 patients (3%) developed only pulmonary embolism, and 7 patients (7%) developed both deep vein thrombosis and pulmonary embolus. Of the 27 patients who developed deep vein thrombosis, 9 (33%) were asymptomatic at the time of diagnosis, and none of these developed a pulmonary embolus or other bleeding complications. There were 2 (2%) events of major postoperative bleeding related to therapeutic anticoagulation. Conclusions The incidence of venous thromboembolism is high (32%) among patients undergoing surveillance after pleurectomy for mesothelioma. Up to 33% of patients with deep vein thrombosis are asymptomatic at the time of diagnosis, and the incidence of complications related to anticoagulation is low. Routine surveillance may be useful to diagnose and treat deep vein thrombosis before it progresses to symptomatic or fatal pulmonary embolus.

Fires occur in most terrestrial ecosystems where they drive changes in the traits, composition, and diversity of fungal communities. Fires range from rare, stand-replacing wildfires to frequent, prescribed fires used to mimic natural fire regimes. Fire regime factors, including burn severity, fire intensity, and timing, vary widely and likely determine how fungi respond to fires. Despite the importance of fungi to post-fire plant communities and ecosystem functioning, attempts to identify common fungal responses and their major drivers are lacking. This synthesis addresses this knowledge gap and ranges from fire adaptations of specific fungi to succession and assembly fungal communities as they respond to spatially heterogenous burning within the landscape. Fires impact fungi directly and indirectly through their effects on fungal survival, substrate and habitat modifications, changes in environmental conditions, and/or physiological responses of the hosts with which fungi interact. Some specific pyrophilous, or "fire-loving," fungi often appear after fire. Our synthesis explores whether such taxa can be considered cosmopolitan, and whether they are truly fire-adapted or simply opportunists adapted to rapidly occupy substrates and habitats made available by fires. We also discuss the possible inoculum sources of post-fire fungi and explore existing conceptual models and ecological frameworks that may be useful in generalizing fungal fire responses. We conclude with identifying research gaps and areas that may best transform the current knowledge and understanding of fungal responses to fire.

Fire can impact terrestrial ecosystems by changing abiotic and biotic conditions. Short fire intervals maintain grasslands and communities adapted to frequent, low-severity fires. Shrub encroachment that follows longer fire intervals accumulates fuel and can increase fire severity. This patchily distributed biomass creates mosaics of burn severities in the landscape—pyrodiversity. Afforded by a scheduled burn of a watershed protected from fires for 27 years, we investigated effects of woody encroachment and burn severity on soil chemistry and soil-inhabiting bacteria and fungi. We compared soils before and after fire within the fire-protected, shrub-encroached watershed and soils in an adjacent, annually burned and non-encroached watershed. Organic matter and nutrients accumulated in the fire-protected watershed but responded less to woody encroachment within the encroached watershed. Bioavailable nitrogen and phosphorus and fungal and bacterial communities responded to high-severity burn regardless of encroachment. Low-severity fire effects on soil nutrients differed, increased bacterial but decreased fungal diversity and effects of woody encroachment within the encroached watershed were minimal. High-severity burns in the fire-protected watershed led to a novel soil system state distinct from non-encroached and encroached soil systems. We conclude that severe fires may open grassland restoration opportunities to manipulate soil chemistry and microbial communities in shrub-encroached habitats.

Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas., Maroni, Bassal, Krishnan et al. characterise human non-small cell lung cancer (NSCLC) carrying Kras-mutations by single-cell RNA sequencing. They identify a tumour-specific population that is conserved in mice and responds to the drug, PTC596, which is currently in clinical trials and may offer a potential avenue for treating aggressive NSCLC expressing mutated Kras.

INTRODUCTION: The diagnosis and treatment of lung cancer is challenged by complex diagnostic pathways and fragmented care that can lead to care disparities for vulnerable patients. METHODS: A multi-institutional, multidisciplinary conference was convened to address the complexity of lung cancer care particularly in patients at high-risk for treatment delay. The resulting care delivery model, called the Lung Cancer Strategist Program (LCSP), was led by a thoracic-trained advanced practice provider (APP) with emphasis on expedited surgery and early oncologic consultation in the assessment of a newly diagnosed suspicious lung nodule. We performed a retrospective review to evaluate care efficiency and oncologic outcomes in the first 100 LCSP patients compared to 100 concurrent patients managed via routine surgical referral. RESULTS: In the 78 LCSP and 41 routine referral patients managed via nodule surveillance, LCSP patients had a shorter time from suspicious finding to work-up (3 vs. 26 days, p < 0.001) and to surveillance decision (12.5 vs. 39 days, p < 0.001). In the 22 LCSP and 59 routine referral patients treated for intrathoracic malignancy, LCSP patients had fewer hospital visits (4 vs 6, p < 0.001), clinicians seen (1.5 vs. 2, p = 0.08), and diagnostic studies (4 vs 5, p = 0.01) with a shorter time to diagnosis (30.5 vs. 48 days, p = 0.02) and treatment (40.5 vs. 68.5 days, p = 0.02). CONCLUSIONS: Patient triage through a thoracic-trained APP in consultation with surgical, medical, and radiation oncology facilitates rapid assessment of benign versus malignant lesions with reduced time to diagnosis and treatment, even among patients at high-risk for treatment delay.

We analyzed the association between neoadjuvant chemoradiation in patients undergoing bronchial sleeve resection with the incidence of postoperative pulmonary and airway complications.After instructional review board approval we performed a retrospective review of a prospectively maintained database of 136 patients who underwent sleeve resection in our institution between January 1998 and December 2016. Administration of neoadjuvant chemoradiation treatment was the studied exposure. Outcomes of interest were rates of postoperative pulmonary and airway complications. Nonparametric testing of demographic, surgical, and pathologic characteristics and morbidity was performed. Logistic regression models evaluated postoperative pulmonary complications and airway complications. Analysis was performed using Stata/IC 15.We analyzed 136 patients (18 underwent neoadjuvant chemoradiation), 77 (57%) of whom had non-small cell lung cancer. Postoperative pulmonary complications were observed in 44 of 136 patients (32%). Incidences of pulmonary complications were higher in the neoadjuvant chemoradiation group compared with the non-neoadjuvant radiation group (15/18 patients [83%] vs 29/118 patients [25%], respectively; P .001). Likewise, rates of pneumonia, atelectasis, respiratory insufficiency, bronchial stenosis, prolonged air leak, bronchopleural fistula, and completion pneumonectomy (2/18 [11%]) were higher in the neoadjuvant chemoradiation group, reaching statistical significance in all cases except bronchial stenosis and prolonged air leak. Only neoadjuvant chemoradiation therapy remained significant for postoperative pulmonary and airway complications on logistic regression (both P.05) CONCLUSIONS: Patients who undergo neoadjuvant chemoradiation before sleeve resection are at an increased risk of pulmonary and airway complications.

Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.

Effective leakage models are crucial for leakage assessment and control strategies to improve the\ud sustainability of vital water distribution, and other pipeline, infrastructure. This paper evaluates the\ud interdependence of leak hydraulics, structural dynamics and soil hydraulics, particularly considering\ud the significance of the soil conditions external to longitudinal slits in viscoelastic pipe. Initial\ud numerical exploration and unique physical experimental results are presented exploring this complex\ud physical phenomenon. The existence of an idealised fully restrained porous medium was shown to\ud significantly increase the pressure- and time-dependent leak opening area whilst reducing the leak\ud flow-rate, compared to a leak into water only. The research highlights the limitation of existing\ud dynamic leakage modelling approaches which greatly simplify or neglect the influence of the soil\ud conditions. Incorporation of this understanding into leakage modelling will enable more accurate\ud estimation of leakage rates and hence the effects of management and control strategies.

Accurate models are critical for the effective management of leaks in our water distribution systems. The increased use of plastic pipes has emphasised the need to assess the ability of current leakage assessment tools in quantifying the real losses from complex time and pressure dependent leaks. The numerical study presented in this paper shows that traditional Minimum Night Flow (MNF) analyses provide good approximations of the leak response, when the loading history and discrete pressure regimes are accounted for, of leaks in viscoelastic pipe. The time and dependent nature of such leaks are of greater significance when the response to short time period pressure transients are quantified, important for active leakage control methodologies in particular.

It has been hypothesised that negative transient pressures may result in ingress of contaminated groundwater through leakage orifices. This paper presents results of contaminant ingress tests from a novel laboratory facility at the University of Sheffield. An engineered leak surrounded by porous media was subjected to a pressure transient resulting from the rapid closure of an upstream valve. It has been shown that a pollutant originating externally was drawn in and transported to the end of the pipe loop. Thus this paper presents the first fully representative results of contaminant ingress.

Strategies for managing leakage from water distribution systems require the ability to effectively evaluate such real losses through the understanding of the behavior of individual leaks, including their response to changes in pressure regime due to demand or management strategies. This paper presents the results from an innovative experimental investigation aimed at understanding the response of longitudinal slits in pressurized viscoelastic pipes, specifically considering the interaction between the structural and leakage dynamics. For the first time, leakage flow rate, pressure, leak area, and material strain were recorded simultaneously, providing new knowledge of the complex interaction of these factors. The paper shows that strain and area are directly related, hence it is possible to employ strain as a predictor of leak area, calculated using a calibrated viscoelastic model. Using such an approach, the leakage flow rates under a range of quasi-static pressures were accurately predicted and validated. Overall the paper demonstrates that the orifice equation, with a constant coefficient of discharge, is suitable for accurately estimating dynamic leakage flow rates from longitudinal slits, provided that the leak area is suitably incorporated.\ud \ud \ud

It is increasingly common for pupils with Down's syndrome to be offered places in mainstream primary schools. However, there is still much to learn about the impact of these placements upon children and classrooms. Recently the Nuffield Foundation funded a two-year research project exploring the inclusion of primary-aged pupils with Down's syndrome. The research focused on the inclusion of 18 pupils with Down's syndrome who attended mainstream primary schools in six local education authorities (LEAs) in the north-west of England. The research team investigated the ways in which schools manage the inclusion of pupils with Down's syndrome and the factors that contribute to the success of mainstream placements. In this article, Sam Fox, Peter Farrell and Pauline Davis from the University of Manchester discuss some of the findings from the study. These concern the support in place for the child and the attitudes of staff, other pupils and the parents of peers towards the inclusion of the child with Down's syndrome. Evidence from the 18 case studies suggests that there is no single way to guarantee effective inclusion. The extent to which a child is effectively included in a mainstream class is likely to be influenced by a number of key factors, including the way in which the teaching assistant (TA) works with the class teacher. Inclusion is more likely to be successful when the class teacher takes a central role in the management of support and the organisation of a child's daily educational experiences. [ABSTRACT FROM AUTHOR]

Many forms of stress, including psychosocial stress, may be associated with reproductive dysfunction. Women seeking treatment for infertility often have been subjected to multiple stressors. The authors have developed an experimental primate model of hypothalamic amenorrhea. Combining mild psychosocial stress with a mild diet and moderate exercise suppresses reproductive function in this model. Because serotonergic activity is decreased in persons who are inordinately sensitive to stress, a study was planned to determine whether differences in endogenous function of the central serotonergic system can be found in stress-sensitive and stress-resistant female cynomolgus macaques. Sedated monkeys previously categorized as highly stress-resistant (HSR, normal menstrual cyclicity through 2 stress cycles), medium stress-resistant (MSR, ovulatory in only the first cycle), or stress-sensitive (SS, anovulatory when first exposed to stress) were challenged with an intravenous dose of 5 mg/kg of the serotonin-releasing drug fenfluramine. The hypothesis was that SS animals would have lower levels of central serotonergic activity. Thyrotropin-releasing hormone (TRH) was administered to control for differences in pituitary stores of prolactin or corticotropin-releasing factor (CRF) to control for low levels of ACTH. Release of prolactin in response to fenfluramine was significantly greater in the HSR animals than in the MSR and SS groups. Cortisol responses to fenfluramine were higher in the SS group than in either group of stress-resistant animals. Similar responses to fenfluramine were no longer evident after stimulation with TRH combined with CRF. These studies in macaques indicate differing reproductive hormone responses to moderate stress. Stress sensitivity correlates with prolactin secretion in response to fenfluramine, which promotes the release of serotonin. Highly stress-resistant animals have higher endogenous serotonin levels than do stress-sensitive animals in the absence of stress. Whether this reflects secretion of ovarian steroids, social status, or genetic predisposition remains to be determined.

Objective To use a nonhuman primate model and determine whether individuals sensitive to stress-induced reproductive dysfunction have lower activity of central serotonergic neurons under nonstressed conditions. Design The activity of the central serotonergic system was assessed by measuring responsiveness to a fenfluramine challenge (5 mg/kg, IV) in sedated monkeys previously categorized as highly stress resistant (HSR; n=4; normal menstrual cyclicity through two stress cycles), medium stress resistant (MSR; n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e., stress sensitive, SS; n=4; anovulatory as soon as stress is initiated). To control for differences in pituitary stores of prolactin or ACTH, the animals were subsequently administered a bolus of thyrotropin-releasing hormone (3 μg/kg) plus corticotropin releasing factor (CRF), (3 μg/kg). Setting Oregon National Primate Research Center, Animal Services Building. Patient(s) Female cynomolgus macaques exhibiting normal menstrual cycles. Intervention(s) Administration of fenfluramine, a serotonin-releasing drug. Main outcomes measure(s) Serum concentrations of prolactin (PRL) and cortisol (F). Result(s) Prolactin release in response to fenfluramine was significantly greater in the HSR group compared with the MSR or SS groups. In contrast, cortisol was higher in the SS group compared with the other two groups. Similar responses were not evident after thyrotropin-releasing hormone + CRF stimulation. Conclusion(s) The lower PRL response to fenfluramine in the stress-sensitive animals suggests that stress-sensitive individuals have decreased activity in central serotonergic neurons. However, the F data suggest that the hypothalamic-pituitary-adrenal axis in stress-sensitive individuals is highly responsive to even small increases in serotonin.