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.

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.

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.

What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

BACKGROUND: Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. METHOD: An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. RESULTS: MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. CONCLUSIONS: MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

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.

Comparing early and delayed repair of common bile duct injury to identify clinical drivers of outcome and morbidity.

BACKGROUND: Outcomes following repair of common bile duct injury (CBDI) are influenced by center and surgeon experience. Determinants of morbidity related to timing of repair are not fully described in this population. METHODS: Patients with CBDI managed surgically at a single center from January 2008 to June 2015 were retrospectively reviewed. Outcomes of patients undergoing early (≤48 h from injury) and delayed (>48 h) repair were compared. Predictive modeling for readmission was performed for patients undergoing delayed repair. RESULTS: In total, 61 patients underwent surgical biliary reconstruction. Between the early and delayed repair groups, no differences were found in patient demographics, injury classification subtype, vasculobiliary injury (VBI) incidence, hospital length of stay, 30-day readmission rate, or 90-day mortality rate. Patients undergoing delayed repair exhibited increased chance of readmission if VBI was present or if multiple endoscopic procedures were performed prior to repair. A predictive model was constructed with these variables (ROC 0.681). CONCLUSION: When managed by a tertiary hepatopancreatobiliary center, equivalent outcomes can be realized for patients undergoing early and delayed repair of CBDI. Establishment of evidence-based consensus guidelines for evaluation and treatment of CBDI may allow identification of factors that drive morbidity and predict clinical outcomes in this population.

A longitudinal study of cortical changes and their cognitive correlates in patients followed up after first-episode psychosis.

BACKGROUND: Loss of cortical volume in frontotemporal regions occurs in patients with first-episode psychosis (FEP) and longitudinal studies have reported progressive brain volume changes at different stages of the disease, even if cognitive deficits remain stable over time. We investigated cortical changes in patients over the 2 years following their FEP and their associations with clinical and cognitive measures. METHOD: Twenty-seven patients after their FEP (20 with schizophrenia, seven with schizo-affective disorder) and 25 healthy controls matched for age and gender participated in this study. Magnetic resonance imaging (MRI) was performed on a 1.5-T scanner both at baseline and after 2 years. Area and thickness of the cortex were measured using surface-based morphometry (SBM). Patients also underwent neuropsychological testing at these two time points. RESULTS: Progressive cortical thinning in the superior and inferior frontal and, to a lesser extent, superior temporal cortex was observed in patients. Cortical area remained constant. Cortical thinning was associated with duration of treatment at a trend level and was predicted by baseline measures of IQ and working memory. Cortical thinning occurred in the absence of clinical or cognitive deterioration. CONCLUSIONS: The clinical implications of these cortical changes remain uncertain, but patients with less cognitive reserve may be more vulnerable to developing cortical abnormalities when exposed to medication or other disease-related biological factors.

Reflection impulsivity and response inhibition in first-episode psychosis: relationship to cannabis use.

BACKGROUND: People with psychosis demonstrate impaired response inhibition on the Stop Signal Task (SST). It is less clear if this impairment extends to reflection impulsivity, a form of impulsivity that has been linked to substance use in non-psychotic samples. METHOD: We compared 49 patients with first-episode psychosis (FEP) and 30 healthy control participants on two forms of impulsivity measured using the Information Sampling Test (IST) and the SST, along with clinical and IQ assessments. We also compared those patients who used cannabis with those who had either given up or never used. RESULTS: Patients with FEP had significantly greater impairment in response inhibition but not in reflection impulsivity compared with healthy controls. By contrast, patients who reported current cannabis use demonstrated greater reflection impulsivity than those that had either given up or never used, whereas there were no differences in response inhibition. CONCLUSIONS: These data suggest that abnormal reflection impulsivity is associated with substance use in psychosis but not psychosis itself ; the opposite relationship may hold for response inhibition.

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.

Improved serological response to H1N1 monovalent vaccine associated with viral suppression among HIV-1-infected patients during the 2009 influenza (H1N1) pandemic in the Southern Hemisphere.

OBJECTIVES: Patients infected with HIV-1 were targeted for vaccination against H1N1 influenza because of their anticipated increased risk of mortality associated with H1N1 infection. Reports regarding the efficacy of vaccination in HIV-1-infected patients have suggested a reduced immunogenic response compared with the general population. Hence, the study aimed to determine the serological response to pandemic H1N1 influenza vaccine in HIV-1-infected patients in a clinical setting. METHODS: A retrospective review of all HIV-1-infected patients who attended mass H1N1 vaccination between October 2009 and March 2010 at an Australian HIV clinic was carried out. Pre- and post-vaccination H1N1 antibody titres were measured. The main outcome measure was response to the vaccination, which was defined as an H1N1 antibody titre of ≥ 1:40 using a haemagglutination inhibition (HI) assay. RESULTS: Baseline blood samples were collected from 199 patients, of whom 154 agreed to receive vaccination; of these, 126 had pre- and post-vaccination HI titres measured. Seventy-seven of 199 patients (38.7%) showed a baseline antibody titre of ≥ 1:40. Eighty-five (67.4%) showed a fourfold or greater increase in titre and 109 of 126 (86.5%) achieved an antibody titre of ≥ 1:40 after vaccination. The serum HI H1N1 antibody geometric mean titre (GMT) for the 126 paired samples was 39.32 ± 3.46 pre-vaccination and increased to 237.36 ± 3.94 [standard deviation (SD)] post-vaccination (P<0.001). In a binary logistic regression analysis, HIV viral load and baseline HI antibody titre were significantly associated with post-vaccination increase in HI H1N1 antibody titre. CONCLUSIONS: A high prevalence of HI H1N1 antibodies was found before vaccination in the cohort, consistent with previous exposure to H1N1 influenza virus. The response to vaccination was considered adequate, as more than two-thirds of patients achieved a fourfold or more increase in antibody titre after vaccination. The response to vaccination was significantly greater in those patients who were aviraemic for HIV, suggesting that antiretroviral therapy improves the humoral response, which is important in optimizing vaccine effectiveness.

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.

Abnormal negative feedback processing in first episode schizophrenia: evidence from an oculomotor rule switching task.

BACKGROUND: Previous studies have shown that patients with schizophrenia are impaired on executive tasks, where positive and negative feedbacks are used to update task rules or switch attention. However, research to date using saccadic tasks has not revealed clear deficits in task switching in these patients. The present study used an oculomotor 'rule switching' task to investigate the use of negative feedback when switching between task rules in people with schizophrenia. METHOD: A total of 50 patients with first episode schizophrenia and 25 healthy controls performed a task in which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. Rule changes were heralded by an unexpected negative feedback, indicating that the cue-response mapping had reversed. RESULTS: Schizophrenia patients were found to make increased errors following a rule switch, but these were almost entirely the result of executing saccades away from the location at which the negative feedback had been presented on the preceding trial. This impairment in negative feedback processing was independent of IQ. CONCLUSIONS: The results not only confirm the existence of a basic deficit in stimulus-response rule switching in schizophrenia, but also suggest that this arises from aberrant processing of response outcomes, resulting in a failure to appropriately update rules. The findings are discussed in the context of neurological and pharmacological abnormalities in the conditions that may disrupt prediction error signalling in schizophrenia.

Medication prescribed to people with personality disorder: the influence of patient factors and treatment setting.

OBJECTIVE: To examine the extent of use and clinical rationale for the prescribing of psychotropic drugs for people with personality disorder (PD) who are in contact with mental health services. METHOD: Clinical records of 278 patients with a primary diagnosis of PD were examined. RESULTS: Just over 80% (N = 225) of patients were being prescribed psychotropic medication. One in five was prescribed three or more drugs. People with comorbid mental disorders were more likely to receive psychotropic medication. Half those prescribed antidepressants had no record of depression in their records. While drug treatments were mostly prescribed for depressive and psychotic symptoms, they were also used to try to manage behavioural problems such as self-harm or given in response to patient requests for treatment. People receiving specialist PD services (OR = 0.35, 95% CI = 0.13-0.95) or other specialist services (OR = 0.24, 95% CI = 0.10-0.60) were less likely to be prescribed drug treatments. CONCLUSION: Drug treatments are widely used for people with PD despite the relatively weak evidence base. Both the type of personality problem and the context in which treatment is delivered appear to have an impact on whether drug treatments are prescribed.

Nature and quality of antipsychotic prescribing practice in UK psychiatry of intellectual disability services.

BACKGROUND: Antipsychotics are perceived to be over-used in the management of behavioural problems in people with an intellectual disability (ID). Published guidelines have set good practice standards for the use of these drugs for behavioural indications. We sought to identify the range of indications for which antipsychotic drugs are prescribed in people with ID and to audit clinical practice against the standards. METHOD: Data were collected from the clinical records of individuals with ID who were under the care of mental health services in the UK, and prescribed an antipsychotic drug. RESULTS: The sample comprised 2319 patients from 39 clinical services. Twenty-seven per cent of the patients had a diagnosis of a psychotic illness (ICD-10 F20-29) and 27% an affective illness (ICD-10 F30-39). The proportion who did not have a psychiatric diagnosis ranged from 6% of those with borderline/mild ID to 21% of those with severe/profound ID. Overall, the most common indications for prescribing an antipsychotic drug were comorbid psychotic illness, anxiety and agitation, and a range of behavioural disturbances. The prevalence of use of antipsychotic drugs to manage challenging behaviour in the absence of concomitant mental illness increased with the severity of ID and accounted for almost half of prescriptions in those with severe/profound ID. Adherence to the audit standards related to documentation of clinical indications and review of efficacy was high. Side effect monitoring was less assiduous. CONCLUSIONS: In clinical practice, most prescriptions for antipsychotic drugs in people with ID are consistent with the evidence base and the overall quality of prescribing practice, as measured against recognised standards, is good, although in some patients potentially remedial side effects may not be detected and treated.

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.

Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function.

Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. We then compared our study (Charing Cross Hospital prospective collection) with that of an independent prefrontal cortex dataset from the Harvard Brain Bank. We report the first direct comparison between two independent studies. A total of 51 gene expression changes have been identified that are common between the schizophrenia cohorts, and 49 show the same direction of disease-associated regulation. In particular, changes were observed in gene sets associated with synaptic vesicle recycling, transmitter release and cytoskeletal dynamics. This strongly suggests multiple, small but synergistic changes in gene expression that affect nerve terminal function.