Technology-enabled multidisciplinary team in-reach for oral corticosteroid stewardship and optimizing care of suspected airways disease exacerbations.

Overuse of corticosteroids is an important problem not only in asthma but also the management of other airways diseases including bronchiectasis and COPD and results in associated risks of serious side effects and irreversible harm. We report a pilot using an in-reach solution to review patients, optimise their care and facilitate early discharge. We discharged >20% of our patients immediately, which is potentially a significant reduction in hospital bed use and, most importantly, through this approach we were able to establish early diagnosis and reduce inappropriate oral corticosteroid use.

A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

A novel digital method to assess air space loss associated with acute lung injury in experimental acute pancreatitis.

BACKGROUND/OBJECTIVES: Respiratory dysfunction and/or failure from acute lung injury (ALI) are common in acute pancreatitis (AP), but assessment of ALI in experimental AP has lacked standardisation. METHODS: A range of experimental AP models induced in C57BL/6 mice with corresponding controls (n = 6/group). Full double lung or right lung specimens were taken for histopathological assessment and slides analysed by a pre-set pipeline using Aperio Scanner (Leica), ImageJ software and CellProfiler software. Findings were compared to other routinely assessed parameters. RESULTS: Overall histopathological changes were similar between both lungs. Mean lung field occupancy was significantly different between moderate and severe CER-AP (21.9% v 27.5%, p < 0.05) and corresponded with lung MPO and local injury severity parameters and was mirrored for all models tested. CONCLUSION: We have developed a novel, simple method for assessment of ALI to improve measurement of systemic organ injury in experimental AP and contribute to preclinical drug development.

Proinflammatory cytokine interferon-γ and microbiome-derived metabolites dictate epigenetic switch between forkhead box protein 3 isoforms in coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong T helper type 1 (Th1)/Th17 immune response in the small intestine. Regulatory T cells (Treg ) are CD4+ CD25++ forkhead box protein 3 (FoxP3+ ) cells that regulate the immune response. Conversely to its counterpart, FoxP3 full length (FL), the alternatively spliced isoform FoxP3 Δ2, cannot properly down-regulate the Th17-driven immune response. As the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FoxP3 isoforms may be associated with the disease. Intestinal biopsies from patients with active CD showed increased expression of FOXP3 Δ2 isoform over FL, while both isoforms were expressed similarly in non-coeliac control subjects (HC). Conversely to what we saw in the intestine, peripheral blood mononuclear cells (PBMC) from HC subjects did not show the same balance between isoforms. We therefore hypothesized that the intestinal microenvironment may play a role in modulating alternative splicing. The proinflammatory intestinal microenvironment of active patients has been reported to be enriched in butyrate-producing bacteria, while high concentrations of lactate have been shown to characterize the preclinical stage of the disease. We show that the combination of interferon (IFN)-γ and butyrate triggers the balance between FoxP3 isoforms in HC subjects, while the same does not occur in CD patients. Furthermore, we report that lactate increases both isoforms in CD patients. Collectively, these findings highlight the importance of the ratio between FoxP3 isoforms in CD and, for the first time, associate the alternative splicing process mechanistically with microbial-derived metabolites.

Changes of haemogram and serum biochemistry in neonatal piglet diarrhoea associated with porcine rotavirus type A.

Porcine rotavirus type A (RVA) is a major cause of neonatal piglet mortality in India. The effect of the disease on haemogram and serum biochemical profile is not well established in piglets. Accordingly, we assessed the haemogram and serum biochemical profile in the neonatal piglet diarrhoea with RVA infection (n = 17). The diagnosis of RVA was confirmed using RNA-polyacrylamide gel electrophoresis (RNA-PAGE), commercially available enzyme-linked immunosorbent assay (ELISA) kit and reverse transcription-polymerase chain reaction (RT-PCR). Non-infected healthy piglets (n = 6) served as control. The concentrations of total protein, albumin, alanine amino transaminase (ALT), aspartate amino transaminase (AST), blood urea nitrogen (BUN) and creatinine in serum were measured by spectrophotometric method. Haemogram was done in the blood using sodium ethylenediaminetetraacetic acid (Na2 EDTA) as anticoagulant. The mean values of total protein, albumin and globulin concentrations were significantly (P < 0.001) decreased and concentrations of ALT, AST, BUN and creatinine were significantly increased (P < 0.001) in the RVA-infected piglets. Haemogram showed marked haemoconcentration (P < 0.001), leukopenia (P < 0.01) and neutropenia (P < 0.01) in the presence of RVA infection than healthy piglets. The results indicated a possible extra-intestinal spread of RVA in piglets during neonatal diarrhoea. The finding might be helpful to clinicians and while treating such type of clinical cases, incorporation of organ protective drugs will be helpful for better response in the treatment schedule.

Candidate Elastic Quantum Critical Point in LaCu_{6-x}Au_{x}.

The structural properties of LaCu_{6-x}Au_{x} are studied using neutron diffraction, x-ray diffraction, and heat capacity measurements. The continuous orthorhombic-monoclinic structural phase transition in LaCu_{6} is suppressed linearly with Au substitution until a complete suppression of the structural phase transition occurs at the critical composition x_{c}=0.3. Heat capacity measurements at low temperatures indicate residual structural instability at x_{c}. The instability is ferroelastic in nature, with density functional theory calculations showing negligible coupling to electronic states near the Fermi level. The data and calculations presented here are consistent with the zero temperature termination of a continuous structural phase transition suggesting that the LaCu_{6-x}Au_{x} series hosts an elastic quantum critical point.

Targeted inhibition of galectin 1 by thiodigalactoside dramatically reduces body weight gain in diet-induced obese rats.

BACKGROUND: Galectin 1 (GAL1), an animal lectin is well characterized in the context of cancer, tumor environment, but its physiological roles in obesity remain to be demonstrated. In this study, we investigated whether targeted inhibition of GAL1 prevents obesity based on the previous observations that GAL1 is highly expressed in adipose tissues of high-fat diet (HFD)-induced obese rats. METHODS: Lipogenic capacity of Lgals1 knocked down adipocytes was evaluated by determining the expression levels of major lipogenic markers using real-time PCR and immunoblot analysis. GAL1 partner proteins were identified using co-immunoprecipitation followed by protein mass fingerprinting. Finally, inhibitory effect of GAL1 by thiodigalactoside (TDG) was assessed in adipocytes and HFD-induced obese rats. RESULTS: Knockdown of GAL1-encoding gene (Lgals1) attenuated adipogenesis and lipogenesis in both 3T3-L1 and HIB1B adipocytes. Further, direct treatment with TDG, a potent inhibitor of GAL1, to cultured adipocytes in vitro significantly reduced fat accumulation. Our animal experiment revealed that intraperitoneal injection of TDG (5 mg kg(-1)) once per week for 5 weeks in Sprague-Dawley (SD) rats resulted in dramatic inhibition of HFD-induced body weight gain (27.3% reduction compared with HFD-fed controls) by inhibiting adipogenesis and lipogensis as well as by increasing expression of the proteins associated with thermogenesis and energy expenditure. CONCLUSION: GAL1 has an essential role in HFD-induced obesity development. From a clinical viewpoint, pharmaceutical targeting of GAL1 using TDG and other inhibitor compounds would be a novel therapeutic approach for the treatment of obesity.

Computational microscopic imaging for malaria parasite detection: a systematic review.

Malaria, being an epidemic disease, demands its rapid and accurate diagnosis for proper intervention. Microscopic image-based characterization of erythrocytes plays an integral role in screening of malaria parasites. In practice, microscopic evaluation of blood smear image is the gold standard for malaria diagnosis; where the pathologist visually examines the stained slide under the light microscope. This visual inspection is subjective, error-prone and time consuming. In order to address such issues, computational microscopic imaging methods have been given importance in recent times in the field of digital pathology. Recently, such quantitative microscopic techniques have rapidly evolved for abnormal erythrocyte detection, segmentation and semi/fully automated classification by minimizing such diagnostic errors for computerized malaria detection. The aim of this paper is to present a review on enhancement, segmentation, microscopic feature extraction and computer-aided classification for malaria parasite detection.

What does the general public in the UK know about the risk to a developing foetus if exposed to alcohol in pregnancy? Findings from a UK mixed methodology study.

INTRODUCTION: Foetal alcohol spectrum disorders (FASD) are a set of preventable conditions where the foetus is exposed to alcohol in utero and as a result suffers adverse consequences. To develop a public health strategy related to FASD, it is important to first establish what is known by the public about this condition. This study aimed to assess the current level of knowledge about FASD in the UK general population. METHODS: A mixed methodology study was conducted using a 17-item questionnaire and focus group sessions. Four focus groups were held with an average of 10 people in each group. Semi-structured questions and thematic analysis of interviews alongside quantitative analysis of the questionnaire data was completed. The research was approved by an National Health service (NHS) research ethical committee. RESULTS: A total of 674 people responded to the questionnaire and a majority (86.7%) had heard about FASD, with most receiving their information from the media (26.2%) or from their work (27.7%). Four broad themes emerged. Overall these were: a general lack of knowledge about the subject; information about the subject needed to be personally relevant; there was a need for further education; and there was a lack of clarity in the current guidance on alcohol use in pregnancy. DISCUSSION AND CONCLUSIONS: Currently there appears to be a superficial level of knowledge about FASD in the UK general public. More detailed work in subgroups, such as young women, to identify their specific needs may be necessary before targeted public health and educational interventions can be developed to meet the needs of the general public.

Spin squeezing in a Rydberg lattice clock.

We theoretically demonstrate a viable approach to spin squeezing in optical lattice clocks via optical dressing of one clock state to a highly excited Rydberg state, generating switchable atomic interactions. For realistic experimental parameters, these interactions are shown to generate over 10 dB of squeezing in large ensembles within a few microseconds and without degrading the subsequent clock interrogation.

[Dysphonia and dysphagia after anterior cervical spine surgery]. / Dysphonie und Dysphagie nach anterioren Zugängen zur Halswirbelsäule.

BACKGROUND: Anterior cervical spine surgery is a common procedure for fusions and/or discectomies. Postoperative dysphonia and dysphagia are known complications. In this study, we examined the frequency and outcomes of these complications in this patient population. MATERIALS AND METHODS: Patients planned to receive anterior cervical spine surgery between 01.03.2010 and 28.02.2011 at the Department of Neurosurgery, St. Gallen were prospectively included. Patients were evaluated using laryngoscopy, fiberoptic endoscopic evaluation of swallowing (FEES), voice field measurements and validated questionnaires. RESULTS: From the 53 patients included in the study, 40 had at least one complete follow-up examination. The frequency of postoperative dysphonia due to recurrent nerve palsy was 4/40 (10 %), although this was temporary in 3 patients. FEES revealed a pathological result in 18.9 % of patients. Postoperative Swallowing Quality of Life Questionnaire (Swal-QoL) scores were significantly lower. CONCLUSION: At a frequency of 10 %, dysphonia due to recurrent nerve palsy is a relevant complication in cervical spine surgery, albeit temporary in most cases. Postoperative dysphagia is common and should be evaluated and treated during follow-up.

Design, development, and performance of a versatile graphene epitaxy system for the growth of epitaxial graphene on SiC.

A versatile graphene epitaxy (GrapE) furnace has been designed and fabricated for the growth of epitaxial graphene (EG) on silicon carbide (SiC) in diverse growth environments ranging from high vacuum to atmospheric argon pressure. Radio-frequency induction enables heating capabilities up to 2000 °C, with controlled heating ramp rates achievable up to 200 °C/s. The details of critical design aspects and temperature characteristics of the GrapE system are discussed. The GrapE system, being automated, has enabled the growth of high-quality EG monolayers and turbostratic EG on SiC using diverse methodologies, such as confinement-controlled sublimation (CCS), open configuration, polymer-assisted CCS, and rapid thermal annealing. This showcases the versatility of the GrapE system in EG growth. Comprehensive characterizations involving atomic force microscopy, Raman spectroscopy, and low-energy electron diffraction techniques were employed to validate the quality of the produced EG.

Neighborhood-level social vulnerability and individual-level cognitive and motor functioning over time in older non-Latino Black and Latino adults.

Introduction: Despite known health disparities in cognitive aging, a comprehensive rationale for the increased burden in older minoritized populations including non-Latino Black and Latino adults has yet to be elucidated. While most work has focused on person-specific risk, studies are increasingly assessing neighborhood-level risk. We evaluated multiple aspects of the environmental milieu that may be critical when considering vulnerability to adverse health outcomes. Methods: We investigated associations between a Census-tract derived Social Vulnerability Index (SVI) and level of and change in cognitive and motor functioning in 780 older adults (590 non-Latino Black adults, ∼73 years old at baseline; 190 Latinos, ∼70 years old baseline). Total SVI scores (higher = greater neighborhood-level vulnerability) were combined with annual evaluations of cognitive and motor functioning (follow-up ranged from 2 to 18 years). Demographically-adjusted mixed linear regression models tested for associations between SVI and cognitive and motor outcomes in analyses stratified by ethno-racial group. Results: For non-Latino Black participants, higher SVI scores were associated with lower levels of global cognitive and motor functioning-specifically, episodic memory, motor dexterity and gait-as well as longitudinal change in visuospatial abilities and hand strength. For Latinos, higher SVI scores were associated with lower levels of global motor functioning only-specifically, motor dexterity; there were no significant associations between SVI and change in motor functioning. Discussion: Neighborhood-level social vulnerability is associated with cognitive and motor functioning in non-Latino Black and Latino older adults, although associations appear to contribute to level more so than longitudinal change.

Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project.

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD). METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day. RESULTS: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services. INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Systematic review and meta-analysis of outcomes after intraoperative pancreatic duct stent placement during pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic leakage after pancreaticoduodenectomy is often serious. Although some studies have suggested that stenting the anastomosis can reduce the incidence of this complication, the value of stenting in the setting of pancreaticoduodenectomy remains unclear. METHODS: Studies comparing outcomes of stent versus no stent, and internal versus external stent placement for pancreaticoduodenectomy were eligible for inclusion. Pooled odds ratios (ORs) with 95 per cent confidence intervals were calculated using fixed- or random-effects models. RESULTS: From a search of the literature published between January 1973 and September 2011, five randomized clinical trials (RCTs) and 11 non-randomized observational clinical studies (OCS) involving 1726 patients were selected for inclusion in this review. Meta-analysis of RCTs revealed that placing a stent in the pancreatic duct did not reduce the incidence of postoperative pancreatic fistula. External stents had no advantage over internal stents in terms of clinical outcome. Subgroup analyses revealed that use of an external stent significantly reduced the incidence of pancreatic fistula (RCTs: OR 0·42, 0·24 to 0·76, P = 0·004; OCS: OR 0·43, 0·27 to 0·68, P < 0·001), delayed gastric emptying (RCTs: OR 0·41, 0·19 to 0·87, P = 0·02) and postoperative morbidity (RCTs: OR 0·55, 0·34 to 0·89, P = 0·02) compared with no stent. CONCLUSION: Pancreatic duct stenting did not reduce the incidence of pancreatic fistula and other complications in pancreaticoduodenectomy compared with no stenting. Although no difference was found between external and internal stents in terms of efficacy, external stents seemed to reduce the incidence of pancreatic fistula compared with control.

What's up with WhatsApp in supplementing surgical education: an objective assessment.

INTRODUCTION: This is the first study aimed at objectively quantifying the benefit of virtual education using WhatsApp-based discussion groups. METHODS: A prospective, non-randomised interventional study was undertaken in the Department of General Surgery, at a tertiary care centre in Kolkata, India, with 200 undergraduate students over a period of 5 days each for 2 weeks, with the first week acting as a control arm. A WhatsApp group was created consisting of 197 eligible undergraduates, faculty members and the authors of this study. Each day, three questions were posted on this group. The second week involved an hour-long WhatsApp-based discussion between the participants and the faculty. Responses were recorded and compared for improvements between the two weeks. Participant feedback was collected and analysed. RESULTS: Statistically significant improvements were observed in the study group compared with the control group in rates of one in three, two in three and three in three correct responses (p=0.01649, 0.01146 and 0.00946, respectively). A total of 68 (51.92%) feedback respondents were satisfied with the programme. Convenience of use was the principal reason behind satisfaction in 79 respondents (60.31%), whereas 62 participants (47.33%) reported lack of hands-on training as a major drawback. CONCLUSIONS: WhatsApp was found to be a satisfactory supplement to traditional medical teaching. It can be implemented to fill lapses in medical education, especially in light of the COVID-19 pandemic, which has caused great disruption to traditional teaching methods. Research is needed to assess the feasibility of incorporating it into the curriculum.

What's up with WhatsApp in supplementing surgical education: an objective assessment.

INTRODUCTION: This is the first study aimed at objectively quantifying the benefit of virtual education using WhatsApp-based discussion groups. METHODS: A prospective, non-randomised interventional study was undertaken in the Department of General Surgery, at a tertiary care centre in Kolkata, India, with 200 undergraduate students over a period of 5 days each for 2 weeks, with the first week acting as a control arm. A WhatsApp group was created consisting of 197 eligible undergraduates, faculty members and the authors of this study. Each day, three questions were posted on this group. The second week involved an hour-long WhatsApp-based discussion between the participants and the faculty. Responses were recorded and compared for improvements between the two weeks. Participant feedback was collected and analysed. RESULTS: Statistically significant improvements were observed in the study group compared with the control group in rates of one in three, two in three and three in three correct responses (p=0.01649, 0.01146 and 0.00946, respectively). A total of 68 (51.92%) feedback respondents were satisfied with the programme. Convenience of use was the principal reason behind satisfaction in 79 respondents (60.31%), whereas 62 participants (47.33%) reported lack of hands-on training as a major drawback. CONCLUSIONS: WhatsApp was found to be a satisfactory supplement to traditional medical teaching. It can be implemented to fill lapses in medical education, especially in light of the COVID-19 pandemic, which has caused great disruption to traditional teaching methods. Research is needed to assess the feasibility of incorporating it into the curriculum.

Upregulation of MAPK pathway is associated with survival in castrate-resistant prostate cancer.

BACKGROUND: Recent evidence has implicated the MAP kinase (MAPK) pathway with the development of castrate-resistant prostate cancer (CRPC). We have previously reported gene amplification of critical members of this pathway with the development of castrate-resistant disease. In addition, we have shown that rising Raf-1 expression, with the development of CRPC, influences time to biochemical relapse. We therefore sought to further analyse the role of both Raf-1 and its downstream target MAPK in the molecular pathogenesis of CRPC. METHODS: Protein expression of Raf-1 and MAPK, including their activation status, was analysed using immunohistochemistry in a database of 65 paired tumour specimens obtained before and after the development of CRPC and correlated with other members of the pathway. RESULTS: Patients whose nuclear expression of MAPK rose with the development of CRPC had a significantly shorter median time to death following biochemical relapse (1.40 vs 3.00 years, P=0.0255) as well as reduced disease-specific survival when compared with those whose expression fell or remained unchanged (1.16 vs 2.62 years, P=0.0005). Significant correlations were observed between protein expression of Raf-1 and MAPK with the type 1 receptor tyrosine kinases, Her2 and epidermal growth factor receptor, as well as the transcription factor AP-1 in CRPC tumours. CONCLUSION: We conclude that the Her2/Raf-1/MAPK/AP-1 axis may promote the development of CRPC, leading to early relapse, and reduced disease-specific survival. In addition, members of the pathway may act as novel therapeutic and/or diagnostic targets for prostate cancer.

An outbreak of neonatal sepsis presenting with exanthematous rash caused by Klebsiella pneumoniae.

Newborns often present with skin conditions ranging from transient benign to severe. An occasional cause of neonatal exanthemic rash is infection due to Gram-positive bacteria, but Gram-negative infection is uncommon. We describe an outbreak of sepsis in 10 neonates over a 2-week period, caused by Klebsiella pneumoniae in a level III neonatal intensive care unit (NICU). Seven babies developed an exanthematous maculopapular rash. Molecular analysis by pulsed-field gel electrophoresis showed that all the babies with rash were infected by a single strain of K. pneumoniae which was distinct from the strain recovered from babies without rash.