Plugin-based interoperability and ecosystem management for the MolSSI Driver Interface Project.

The MolSSI Driver Interface (MDI) Project is an effort to simplify and standardize the process of enabling tight interoperability between independently developed code bases and is supported by numerous software packages across the domain of chemical physics. It enables a wide variety of use cases, including quantum mechanics/molecular mechanics, advanced sampling, path integral molecular dynamics, machine learning, ab initio molecular dynamics, etc. We describe two major developments within the MDI Project that provide novel solutions to key interoperability challenges. The first of these is the development of the MDI Plugin System, which allows MDI-supporting libraries to be used as highly modular plugins, with MDI enforcing a standardized application programming interface across plugins. Codes can use these plugins without linking against them during their build process, and end-users can select which plugin(s) they wish to use at runtime. The MDI Plugin System features a sophisticated callback system that allows codes to interact with plugins on a highly granular level and represents a significant advancement toward increased modularity among scientific codes. The second major development is MDI Mechanic, an ecosystem management tool that utilizes Docker containerization to simplify the process of developing, validating, maintaining, and deploying MDI-supporting codes. Additionally, MDI Mechanic provides a framework for launching MDI simulations in which each interoperating code is executed within a separate computational environment. This eliminates the need to compile multiple production codes within a single computational environment, reducing opportunities for dependency conflicts and lowering the barrier to entry for users of MDI-enabled codes.

Striving for long term sustainability - Is it time we changed our approach to animal health in low- and middle-income countries?

Animal health and agricultural productivity in low- and middle-income countries have been the focus of research for development (R4D) projects for decades, with varying levels of success when considering the long-term sustainability of interventions. Many of these projects have been funded, designed and implemented by researchers from high income countries, and therefore risk neglecting the cultural nuances and complex country histories that can influence their success. This opinion piece suggests three broad recommendations: (1) implementing culturally congruent practices to improve disease control and prevention practices at the village level; (2) promoting public-private partnerships to improve control of transboundary animal diseases; and (3) improving national animal health and veterinary services and their governance to improve disease surveillance, control and prevention. Development researchers need to consider implementing these approaches in future projects to improve the suitability and sustainability of interventions and acknowledging the current technical capacity of host countries. Foreign donor organisations need to ensure their funding guidelines and reporting requirements allow for these recommendations to be adequately implemented.

Prevalence of Tritrichomonas foetus in beef bulls slaughtered at two abattoirs in northern Australia.

Bovine trichomoniasis, caused by the protozoal parasite Tritrichomonas foetus, is a highly contagious venereal disease characterised by early pregnancy loss, abortion and pyometra. Persistently infected bulls and cows are the primary reservoirs of infection in infected herds. This research investigated the prevalence of T. foetus infection in bulls from properties located across northern Australia and New South Wales. Preputial samples were collected from 606 bulls at slaughter and tested for T. foetus using the VetMAX-Gold Trich Detection Kit (Thermo Fisher Scientific). The apparent prevalence of T. foetus infection varied between regions, with northern regions in the Northern Territory, Queensland and Western Australia showing a prevalence of 15.4%, 13.8% and 11.4%, respectively. There was some evidence of an association between infection and postcode (P = 0.06) and increasing bull age (P = 0.054). This study confirms that T. foetus infection is likely to be present in many beef breeding herds and contributing to lower than expected reproductive performance, particularly across northern Australia.

Pathogens associated with pleuritic pig lungs at an abattoir in Queensland Australia.

OBJECTIVE: Pleurisy in pigs has economic impacts in the production stage and at slaughter. This study sought to establish if some micro-organisms can be found in high numbers in lungs with pleurisy by assessing batches of pigs at an abattoir in Queensland Australia. DESIGN: Samples of lung (including trachea/bronchus and lymph nodes) from a maximum of 5 pleurisy affected pigs were collected from 46 batches of pigs representing 46 Queensland farms. PROCEDURE: Pleurisy-affected lung areas were cultured by traditional bacteriological methods and bacteria quantified by plate scores. Additionally, tracheal or bronchial swabs and apical lobe fluid were tested for Mycoplasma hyopneumoniae DNA and the superior tracheobronchial lymph nodes were tested for porcine circovirus type 2 DNA by polymerase chain reaction (PCR). All apparently significant bacteria were identified via PCR or sequencing. Typing was undertaken on some of the bacterial isolates. RESULTS: The most prevalent pathogens were M. hyopneumoniae, Streptococcus suis and Porcine Circovirus type 2, being found in 34, 38 and 31 batches, respectively. Other bacteria found were Actinobacillus species (29 batches), Pasteurella multocida (24 batches), Mycoplasma flocculare (9 batches), Actinobacillus pleuropneumoniae (7 batches), Mycoplasma hyorhinis (4 batches), Bisgaard Taxon 10 (1 batch), Glaesserella parasuis (1 batch), Streptococcus minor (1 batch) and Streptococcus porcinus (1 batch). Most batches had more than one bacterial species. CONCLUSION: The high percentage of batches infected with S. suis (83%), M. hyopneumoniae (74%) and PCV2 (70%) and clustering by a batch of these pathogens, as well as the presence of many secondary pathogens, suggests synergy between these organisms may have resulted in pleurisy.

Prevalence and spatial distribution of Coxiella burnetii seropositivity in northern Australian beef cattle adjusted for diagnostic test uncertainty.

Q fever is a zoonotic disease caused by infection with Coxiella burnetii transmitted from animals including, but not limited to, cattle, sheep and goats. The infection in cattle is typically sub-clinical with some evidence suggesting associated reproductive loss. There is currently limited data on the true prevalence and distribution of coxiellosis in beef cattle across northern Australia. During this study, 2,012 sera samples from beef cattle managed on commercial farms located in Queensland and the Northern Territory were tested using an indirect immunofluorescent assay (IFA) for serological evidence of IgG antibodies against C. burnetii. Bayesian latent class models were used to estimate the true prevalence, adjusted for diagnostic test sensitivity and specificity and incorporating the hierarchical structure of the cattle within farms and regions. In this study, cattle in the Northern Territory had lower estimated true prevalence than cattle within most regions of Queensland with the exception of south-east Queensland. Results from this study have described the geographic distribution and estimated the true prevalence of antibodies to C. burnetii in a sample of extensively managed beef cattle located across the tropical grazing regions of northern Australia.

LGBTQ bullying: a qualitative investigation of student and school health professional perspectives.

Researchers and practitioners have recently called for greater involvement of school health professionals (SHPs; e.g., school psychologists, nurses, guidance counselors) in interventions to identify and address bullying of lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) students. To inform future interventions, this study explored the perspectives of LGBTQ students and SHPs on LGBTQ bullying and SHPs' responses to LGBTQ bullying. Five online, asynchronous focus groups were held in 2018 with 28 LGBTQ students and 19 SHPs recruited from Massachusetts, US. Methods were guided by Rapid Qualitative Inquiry. Results revealed a disconnect in perceptions of LGBTQ bullying among LGBTQ students versus SHPs, with LGBTQ students reporting a range of often significant verbal, social, and physical bullying experiences and SHPs reporting minimal awareness of LGBTQ bullying at their schools. Transgender students reported bullying related to their gender identity, including verbal, physical, and sexual harassment, deadnaming (referred to by their birth name), and misgendering (called an incorrect pronoun). LGBTQ students of color reported bullying based on their race/ethnicity and pronounced social isolation. LGBTQ students reported mixed experiences with reporting bullying to SHPs. Intervention efforts are needed to enhance communication between LGBTQ students and SHPs, and to strengthen SHPs' skills to respond to LGBTQ bullying.

Rapid Access Palliative Radiotherapy Programmes.

One of the greatest successes of radiotherapy has been its ability to palliate symptoms from advanced and metastatic cancers. Unfortunately, patients face barriers to accessing care and the demand for treatment is rising. Rapid access palliative radiotherapy programmes were created in response to these concerns, and over time they have proliferated and succeeded internationally. This narrative review provides an overview of programmes that have published their experiences, and discusses how they have improved access to care, increased evidence-based practice, met the needs of vulnerable populations, advanced the roles of multidisciplinary team members, collaborated across medical specialties, educated trainees and referring physicians, and developed new treatment platforms using advanced technologies.

Genetic analysis of porcine circovirus type 2 (PCV2) in Queensland, Australia.

OBJECTIVE: To determine the current porcine circovirus type 2 (PCV2) genotypes circulating in pigs in Queensland (QLD). METHODS: The PCV2 infection status of pigs was determined by real-time PCR testing of 210 lymph nodes and 30 serum samples derived from 45 QLD farms. PCV2-positive samples from 22 pigs from 15 farms were subjected to conventional polymerase chain reaction (PCR) and sequencing of the full PCV2 genome. Phylogenetic analysis of 17 of these sequences in relation to published PCV2 sequences was then performed, and the genotypes were compared. RESULTS: PCV2 DNA was detected in 95 lymph nodes and 15 serum samples. Phylogenetic analysis of 17 PCV2 sequences demonstrated that seven belonged to genotype PCV2b, two to PCV2d, one to PCV2f and seven to an "intermediate group" that clustered with PCV2d on the full genome analysis. CONCLUSION: This work confirms earlier studies reporting the presence of PCV2b in Australia. It is the first study to report that PCV2d and PCV2f are also present in this country. PCV2d is currently a fast-spreading genotype globally, with reported high virulence. The potential implications of these findings with respect to pathogenicity and vaccine efficacy require further investigation.

Mitigating clinical waste in the trauma intensive care unit: Limited clinical utility of cardiac troponin testing for trauma patients with atrial fibrillation.

BACKGROUND: The clinical significance of obtaining cardiac troponin (cTn) levels among trauma patients with new onset arrhythmias is unknown. We aimed to assess whether cTn levels actually influence clinical decision making or represent an inappropriate use of resources. METHODS: Trauma patients admitted from 2013 to 2014 diagnosed with atrial fibrillation (AF) were retrospectively reviewed using the institutional trauma database. Demographics, cTn levels, and myocardial infarction (MI) diagnosis data were recorded. Standard univariate tests were used to compare data between patients with and without cTn. RESULTS: There were 258 patients included of which 126 patients had cTn levels obtained (48.8%, TEST group). The remaining 132 patients (51.2%) were untested (noTEST group). Among TEST patients, use of echocardiography nearly doubled and cardiology consultations increased (all p < 0.05). No TEST patients suffered MI or PE. CONCLUSIONS: Obtaining cTn values in trauma patients with new-onset AF resulted in increased resource utilization without clinical utility.

A high protein meal affects plasma insulin concentrations and amino acid metabolism in horses with equine metabolic syndrome.

Equine metabolic syndrome (EMS) is characterized by an abnormal insulin response to a glycemic challenge but despite the known insulinotropic effects of certain amino acids, there is a paucity of data evaluating the impact of dietary protein on insulin dynamics in these horses. The objective was therefore to assess insulin and amino acid responses following intake of a high protein meal in healthy horses and those with EMS. Six mature horses diagnosed with EMS and six age-matched control horses without EMS were used. Horses were fed 2g/kg body mass (BM) of a high protein pellet (31% crude protein) at time 0 and 30min, for a total of 4g/kg BM, following an overnight fast. Blood samples collected during a 4h period were analysed for plasma glucose, insulin, amino acids and urea concentrations. Glucose concentrations were not different between groups (P=0.2). Horses with EMS had a 9-fold greater insulinemic response to the consumption of a high protein meal compared with controls (P=0.046). Post-prandial levels of histidine, citrulline, tyrosine, valine, methionine, isoleucine, leucine and ornithine were higher in horses with EMS (P<0.05). Baseline urea nitrogen concentrations were not significantly different between groups (P=0.1). Knowing that certain amino acids are insulin secretagogues, these results illustrate that consumption of a high protein meal caused a hyperinsulinemic response and affected amino acid dynamics in horses with EMS. These findings suggest that dietary protein content should be taken into consideration in the management of horses with insulin dysregulation.

A physiological study to determine the mechanism of carbon dioxide clearance during apnoea when using transnasal humidified rapid insufflation ventilatory exchange (THRIVE).

Clinical observations suggest that compared with standard apnoeic oxygenation, transnasal humidified rapid-insufflation ventilatory exchange using high-flow nasal oxygenation reduces the rate of carbon dioxide accumulation in patients who are anaesthetised and apnoeic. This suggests that active gas exchange takes place, but the mechanisms by which it may occur have not been described. We used three laboratory airway models to investigate mechanisms of carbon dioxide clearance in apnoeic patients. We determined flow patterns using particle image velocimetry in a two-dimensional model using particle-seeded fluorescent solution; visualised gas clearance in a three-dimensional printed trachea model in air; and measured intra-tracheal turbulence levels and carbon dioxide clearance rates using a three-dimensional printed model in air mounted on a lung simulator. Cardiogenic oscillations were simulated in all experiments. The visualisation experiments indicated that gaseous mixing was occurring in the trachea. With no cardiogenic oscillations applied, mean (SD) carbon dioxide clearance increased from 0.29 (0.04) ml.min-1 to 1.34 (0.14) ml.min-1 as the transnasal humidified rapid-insufflation ventilatory exchange flow rate was increased from 20 l.min-1 to 70 l.min-1 (p = 0.0001). With a cardiogenic oscillation of 20 ml.beat-1 applied, carbon dioxide clearance increased from 11.9 (0.50) ml.min-1 to 17.4 (1.2) ml.min-1 as the transnasal humidified rapid-insufflation ventilatory exchange flow rate was increased from 20 l.min-1 to 70 l.min-1 (p = 0.0014). These findings suggest that enhanced carbon dioxide clearance observed under apnoeic conditions with transnasal humidified rapid-insufflation ventilatory exchange, as compared with classical apnoeic oxygenation, may be explained by an interaction between entrained and highly turbulent supraglottic flow vortices created by high-flow nasal oxygen and cardiogenic oscillations.

Mycoplasma bovis and bovine respiratory disease: A risk factor study in Australian feeder cattle.

Mycoplasma bovis can be a bacterial inhabitant of the upper respiratory tract of healthy bovines. In body regions other that the upper respiratory tract however, M. bovis is associated with a number of clinical syndromes such as bovine respiratory disease (BRD). This study used two enzyme-linked immunosorbent assays to assess the sero-status of M. bovis-specific antibodies in Australian feeder cattle at the time of feedlot induction and at approximately 42 days on feed (follow-up). The apparent sero-prevalence of M. bovis-specific antibody at induction was estimated to be 3.5% (95% confidence interval [CI] 2.0-5.0%, 47/1354) and 25.3% (95% CI 21.9-28.8%, 343/1354) at follow-up. Exposure to M. bovis between induction and follow-up as demonstrated by an increase in serum antibodies was estimated to be 19.4% (95% CI 16.2-22.6%, 261/1349). Risk factors associated with sero-positivity at feedlot induction included the region where animals were 28 days prior to induction and saleyard exposure at least 27 days prior to induction. Risk factors associated with a sero-increase between induction and follow-up included breed, source region and access to water shared with an adjoining pen of animals. Of these, shared pen water was considered the most important (odds ratio [OR] 3.3, 95% CI 1.5-7.4, p = 0.003). Animals exposed to M. bovis between induction and follow-up were at a substantially increased risk of BRD (OR 2.2, 95% CI 1.4-3.4, p = 0.001). This is the first Australian study that has identified risk factors for M. bovis sero-positivity and sero-increase and shown an association between sero-increase and the risk of BRD in the feeder cattle population. These findings suggest that M. bovis is a significant pathogen in the Australian feeder cattle population. In addition, identification of defined risk factors associated with an increased risk of exposure to M. bovis can assist in the development of targeted control measures to reduce the economic impact of M. bovis associated disease and BRD in feeder cattle.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors, T790M, and clinical trials.

Tumours with sensitizing mutations in the EGFR gene constitute a distinct molecular subgroup of non-small-cell lung cancers (nsclcs) that benefit from precision medicine. First- and second-generation epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as upfront therapy for EGFR-mutated advanced nsclc and, compared with chemotherapy, have resulted in superior progression-free survival, improved tumour response rates, and improved quality of life. However, resistance inevitably develops, and the third-generation tki osimertinib has been approved to target the gatekeeper EGFR mutation T790M, which is responsible for resistance in 60% of cases. Multiple drivers of tki resistance have now been identified, and many new drugs are in development. With respect to this rapidly evolving field, our review highlights the current status of treatment options for patients with EGFR-mutated advanced nsclc, focusing especially on identified causes of resistance, challenges, and clinical trials aiming to improve outcomes in this patient population.

Developing and validating a center-specific preoperative prediction calculator for risk of pancreaticoduodenectomy.

BACKGROUND: The American College of Surgeons (ACS) Surgical Risk Calculator predicts postoperative risk based on preoperative variables. The ACS model was compared to an institution-specific risk calculator for pancreaticoduodenectomy (PD). METHODS: Observed outcomes were compared with those predicted by the ACS and institutional models. Receiver operating characteristic (ROC) analysis evaluated the models' predictive ability. Institutional models were evaluated with retrospective and prospective internal validation. RESULTS: Brier scores indicate equivalent aggregate predictive ability. ROC values for the institutional model (ROC: 0.675-0.881, P < 0.01) indicate superior individual event occurrence prediction (ACS ROC: 0.404-0.749, P < 0.01-0.860). Institutional models' accuracy was upheld in retrospective (ROC: 0.765-0.912) and prospective (ROC: 0.882-0.974) internal validation. CONCLUSIONS: Identifying higher-risk patients allows for individualized care. While ACS and institutional models accurately predict average complication occurrence, the institutional models are superior at predicting individualized outcomes. Predictive metrics specific to PD center volume may more accurately predict outcomes.

The relationship between negative symptoms and depression in schizophrenia: a systematic review.

OBJECTIVE: To provide an update on the evidence base for the nature of the relationship between negative symptoms and depressive features in people with schizophrenia, and propose new models that reflect their complex relationship. METHOD: A systematic review following PRISMA guidelines. A total of 2210 articles were identified from EMBASE, PsychInfo and MEDLINE, and further two articles were hand-searched from references. Twenty-seven met inclusion criteria and were included in the review. RESULTS: In schizophrenia, primary evidence suggests symptoms of low mood, suicidal ideation and pessimism have more specificity for depression whereas alogia and blunted affect may have more specificity as negative symptoms. Anhedonia, anergia and avolition may be common to both. CONCLUSION: It may be possible to further distinguish depressive features from negative symptoms in schizophrenia when detailed phenomenology is considered. However, in a proposed dimensional model, these two domains continue to share certain phenomena, highlighting their close relationship.

Improved urethral fluorescence during low rectal surgery: a new dye and a new method.

BACKGROUND: The aim of this study was to demonstrate highlighting of the urethra during surgery through the use of two different methods: a new near-infrared fluorophore IRDye800BK, and indocyanine green (ICG) mixed with silicone. METHODS: Male cadavers from the department of anatomy at the University of Oxford were used to visualise the urethra during near-infrared fluorescence excitation. To assess IRDye800BK, a perineal incision was utilised after infiltrating the urethra directly with an IRDye800BK solution mixed with Instillagel. ICG-silicone was assessed when the urethra was purposely exposed as part of a simulated transanal total mesorectal dissection. ICG was previously mixed with ethanol and silicone and left to set in a Foley catheter. Fluorescence was visualised using an in-house manufactured fluorescence-enabled laparoscopic system. RESULTS: IRDye800BK demonstrated excellent penetration and visualisation of the urethra under fluorescence at an estimated tissue depth of 2 cm. An ICG-silicone catheter demonstrated excellent fluorescence without leaving any residual solution behind in the urethra after its removal. CONCLUSIONS: The newly described ICG-silicone method opens up the possibility of new technologies in this area of fluorescence guided surgery. IRDye800BK is a promising alternative to ICG in visualising the urethra using fluorescence imaging. Its greater depth of penetration may allow earlier detection of the urethra during surgery and prevent wrong plane surgery sooner.

Chronic maternal inflammation during late gestation impairs subsequent ß-cell function but not islet growth in fetal sheep.

Intrauterine growth restriction (IUGR) greatly increases perinatal mortality and morbidity rates, and leads to much greater risk for metabolic complications later in life. One such complication is the development of glucose intolerance or diabetes, which typically develops concurrently with abhorrent patterns of insulin secretions due to diminished ß-cell mass and impaired function as well as an overall reduction in pancreatic endocrine tissue. The mechanisms by which IUGR causes problems with health and function of the pancreatic islets are not well understood. Therefore, our goal for this study was to determine how materno-fetal inflammation (MI) affects ß-cell growth and function. To do this, we compared the average islet areas, plasma insulin concentrations, and blood glucose concentrations between MI-IUGR fetal lambs (n = 7) and control fetal lambs (n = 7). Pregnant ewes were injected with saline (controls) or 0.1-µg/kg bacterial lipopolysaccharide (LPS) every 3 d from days 100 to 115 of gestation (term = 150 d). Throughout late gestation, arterial blood of the fetus was periodically drawn and analyzed for plasma insulin (ELISA) and blood glucose (ABL90 FLEX) levels. On day 125 of gestation, ewes were euthanized and fetal pancreas was extracted. Sections of the fetal pancreas were then fixed in 4% paraformaldehyde, sectioned (cryostat) at a thickness of 8 µm, stained for insulin-positive area, and imaged on 20x magnification for analysis of average islet area. Between MI-IUGR and control fetuses, there were no differences in average islet areas (1675 ± 286 and 1678 ± 287 µm2, respectively), which indicates that MI did not impair growth and physical development of fetal islets. In addition, blood glucose was similar in all fetuses. However, results showed less (P ≤ 0.05) plasma insulin concentration in MI-IUGR fetuses (0.39 ± 0.07 ng/mL) than in controls (0.70 ± 0.09 ng/mL). This indicates impaired ß-cell functional capacity in MI-IUGR fetuses despite normal growth, which is quantified by a tendency (P = 0.08) for strong positive correlation (r = 0.91) between plasma insulin and islet area in control fetuses but an absence of correlation in MI-IUGR fetuses. From this study, we can conclude that MI-IUGR has no effect on the growth and physical development of ß cells; however, it does greatly affect their function.

Fluorescence to highlight the urethra: a human cadaveric study.

BACKGROUND: Urethral injury is a complication feared by surgeons performing transanal TME (TaTME) or abdominoperineal excision (APE) procedures. Injury during TaTME occurs when the prostate is inadvertently mobilised or as a direct injury similar to the direct injury during the perineal dissection of APE procedures. We performed a proof of principle study to assess the feasibility of using indocyanine green (ICG) to fluoresce the urethra in human cadavers. METHODS: Indocyanine green at varying doses was mixed with Instillagel and infiltrated into the urethra of male human cadavers. The urethra was exposed through either a perineal incision or by mobilisation of the prostate during a TaTME dissection and fluorescence observed using a PINPOINT laparoscope (NOVADAQ). Brightness was assessed on the images using ImageJ (National Institute of Health). RESULTS: Eight cadavers were included in the study. Fluorescence was visualised in the urethra in all eight cadavers. Minimal dissection was required to obtain fluorescence transperineally. In one cadaver, the urethra was demonstrated under fluorescence using a simulated TaTME with additional fluorescence also being observed in the prostate. There was no correlation between brightness and dosing. CONCLUSIONS: This novel proof of principle study demonstrates a simple way in which the urethra may be easily identified preventing it from injury during surgery.