Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).

BACKGROUND: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. METHODS: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. ETHICS AND DISSEMINATION: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. TRIAL REGISTRATION: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020.

A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.

Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy.

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.

Effects of flock age, storage temperature, and short period of incubation during egg storage, on the albumen quality, embryonic development and hatchability of long stored eggs.

1. The effect of breeder flock age, storage temperature and a short period of incubation during egg storage (SPIDES) on albumen quality, development of blastoderm, and hatchability of long-stored eggs was evaluated.2. Hatching eggs were collected from 28-week-old (young) and 40-week-old (prime) Ross female line grandparent flocks and were stored for 14 d at 12, 15 or 18°C. During storage, the eggs were either kept continuously in the storage room (control) or were subjected to SPIDES treatment.3. Embryonic development was more advanced in eggs from the prime flock, exposed to SPIDES and warmer (18°C) storage temperature (P ≤ 0.05). There was a difference in the albumen pH for flock ages (P < 0.05), but the SPIDES treatment did not affect albumen height and pH (P > 0.05). On d 14 of storage, albumen pH was positively (P < 0.05) correlated with storage temperature. Hatchability was higher in the prime flock (P < 0.05).4. At both flock ages, hatchability increased (P < 0.05) by storing the eggs at 15°C, compared to 18°C, with 12°C intermediate. The hatchability improvement was due to reduced early embryonic mortality.5. The SPIDES treatment decreased late embryonic mortality and the percentage of second-grade chicks (P < 0.05), which increased the hatchability of fertile eggs (P < 0.05). SPIDES only reduced (P < 0.05) early embryonic mortality in eggs stored at 18°C.6. The highest hatchability was observed in the eggs stored at 15°C and exposed to one SPIDES treatment during 14 d storage.

Trainee's Preparedness for Paediatric Work.

Aim Compare the opinion of paediatric consultants to paediatric Senior House Officers (SHOs) with regards their perceived level of preparedness for starting work in paediatrics. Methods A 5-point Likert scale questionnaire was administered to paediatric consultants and SHOs investigating how well they considered the SHO was performing and how well prepared the SHO perceived themselves for work in clinical paediatrics, respectively. Questions related to procedures, clinical examination, teamwork, history taking and OPD related activity. Results 50 Consultants and 75 SHOs completed the questionnaire. Using a Mann-Whitney U test, both groups answered similarly to questions relating to clinical examination and history taking (p=0.51 and p=0.15). However, there were significant differences in their responses to questions relating to procedures, teamwork and OPD related activity (p<0.05). Conclusion There is a significant disparity between consultant opinion of ability and SHOs perception of preparedness for some of the same skills. More work, focusing on these specific aspects of undergraduate paediatric education needs to be carried out to improve graduate preparedness for this role.

Heavy Physics Contributions to Neutrinoless Double Beta Decay from QCD.

Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental effort. Relating nuclear decay rates to high-energy, beyond the standard model (BSM) physics requires detailed knowledge of nonperturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π^{-}→π^{+} exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.

PGAM5 expression and macrophage signatures in non-small cell lung cancer associated with chronic obstructive pulmonary disease (COPD).

BACKGROUND: COPD patients are at increased risk of developing non-small cell lung carcinoma that has a worse prognosis. Oxidative stress contributes to carcinogenesis and is increased in COPD patients due to mitochondrial dysfunction. We determined whether mitochondrial dysfunction is a contributing factor to the reduced survival of COPD patients with non-small cell lung carcinoma (NSCLC). METHODS: Using a transcriptomic database and outcome data of 3553 NSCLC samples, we selected mitochondrial-related genes whose levels in the tumour correlated with patient mortality. We further selected those genes showing a ≥ 2 fold expression in cancer compared to normal tissue. Cell-type specific expression of these proteins in lung tissue from NSCLC patients who were non-smokers or smokers with or without COPD (healthy smokers) was determined by immunohistochemistry. Gene set variation analysis was used in additional NSCLC datasets to determine the relative expression of specific macrophage transcriptomic signatures within lung cancer tissue. RESULTS: The expression of 14 mitochondrial-related genes was correlated with patient mortality and these were differentially expressed between cancer and normal lung tissue. We studied further the expression of one of these genes, PGAM5 which is a regulator of mitochondrial degradation by mitophagy. In background lung tissue, PGAM5 was only expressed in alveolar macrophages, with the highest expression in smokers with COPD compared to healthy smokers and non-smokers. In cancerous tissue, only the malignant epithelial cells and associated macrophages at the periphery of the cancer expressed PGAM5. Pre-neoplastic epithelium also showed the expression of PGAM5. There was no difference in expression in cancer tissue between COPD, healthy smoker and non-smoker groups. Macrophages at the edge of the cancer from COPD patients showed a trend towards higher expression of PGAM5 compared to those from the other groups. There was a significant correlation between PGAM5 expression in cancer tissue and the level of expression of 9 out of 49 previously-defined macrophage transcriptomic signatures with a particular one associated with patient mortality (p < 0.05). CONCLUSION: PGAM5 is expressed in pre-neoplastic tissue and NSCLC, but not in normal epithelium. The association between PGAM5 expression and patient mortality may be mediated through the induction of specific macrophage phenotypes.

Further Reductions in Road-Related Deaths and Injuries in Irish Children.

The aim was to study road-related injuries and fatalities in under 15-year-olds in three time periods (1996-2000, 2004-2008 and 2009 -2013 respectively) to assess whether progress has been made via cross-sectoral efforts (legislation, public awareness campaigns and police enforcement) to reduce this injury toll in Ireland. For road traffic collisions where an injury has occurred, police assistance is required and at the time a detailed CT 68 form is completed by the attending police officer and sent to the Road Safety Authority for analysis. Details regarding the severity of injury, light and road conditions and safety measures such as seat belt or car restraint use, seat position and helmet use if a cyclist is involved are recorded. Injuries were sub-classified as fatalities, serious (detained in hospital, fractures, severe head injury, severe internal injuries or shock requiring treatment) or minor. All data for the three time periods was entered onto an SPSS database. A concerted national campaign re road safety media campaign allied to random breath testing, penalty points for driving offences, on the spot fines for speeding and greater police enforcement took place over the 17-year timeframe and continues to this day. When results were compared between the three cohorts, total injuries dropped from 5928 (1996-2000) to 3903 (2009-2013).Fatal injuries dropped from 163 to 43 with car occupant fatalities fell from 69 to 17 between 1996-2000 and 2009-2013. Serious injuries dropped from 347 in the first cohort to 201 in the third cohort. Minor injuries fell from 5,063 to 3,659 between first and last cohort. Pedestrian injuries dropped from 1719 to 1258 with pedestrian fatalities decreased from 61 (1996-2000) to 21 (2009-2013) and serious pedestrian injuries decreased from 261 down to 129. Cyclist fatalities saw the most significant fall (76%) with a dramatic reduction in fatalities from 25 down to 6. A national road safety campaign, greater police enforcement and a cultural change has seen road-related deaths and injuries in children drop very significantly (by over 70%) over the three time periods (spanning 1996 to 2013) and this campaign should continue.

An entropic model of Gaia.

We modify the Tangled Nature Model of Christensen et. al. (2002) so that the agents affect the carrying capacity. This leads to a model of species-environment co-evolution where the system tends to have a larger carrying capacity with life than without. We discuss the model as an example of an entropic hierarchy and some implications for Gaia theory.

A Survey of Clinical Uncertainty from the Paediatric Basic Specialist Trainee Perspective.

This study was undertaken to evaluate uncertainty from the Basic Specialist Trainee perspective. The survey of trainees explored 1) factors in decision making, 2) the personal impact of uncertainty, 3) the responses to both clinical errors and challenges to their decision making and 4) the potential strategies to address uncertainty. Forty-one (93%) of trainees surveyed responded. Important factors in decision making were clinical knowledge and senior colleague's opinion. Sixty percent experienced significant anxiety post call as a consequence of their uncertainty. When errors are made by colleagues, the trainee's response is acceptance (52.5%), and sympathy (32%).Trainees are strongly influenced by the opinions of senior colleagues often changing their opinions having made confident decisions. Solutions to address uncertainty include enhanced knowledge translation, and to a lesser extent, enhanced personal awareness and resilience awareness. To enhance the training experience for BST and lessen the uncertainty experienced these strategies need to be enacted within the training milieu.

Pulmonary light-chain deposition disease: CT and pathology findings in nine patients.

AIM: To review the clinical features of nine patients with pulmonary light-chain deposition disease (LCDD) and record their high-resolution CT (HRCT) and histopathological findings. MATERIALS AND METHODS: Patients with a diagnosis of LCDD on lung biopsy specimen were retrospectively identified. The HRCT characteristics of nodules, cysts, and ancillary findings; change at follow-up; and histopathological findings were documented. RESULTS: Features common to all nine cases were thin-walled cysts. In seven cases, vessels traversing the cysts were identified. The majority of patients (8/9) had at least one pulmonary nodule. There was no zonal predominance of either cysts or nodules. The disease appeared stable in the majority of cases with no serial change in HRCT appearances (5/6 cases with follow-up data, mean duration 29 months). CONCLUSION: To the authors' knowledge, this is the largest series of pulmonary LCDD patients in the literature, and the first systematic assessment of HRCT findings. Pulmonary cysts are a unifying feature, usually with pulmonary nodules, and serial change on HRCT is unusual.

Sterile 'Judas' carp--Surgical sterilisation does not impair growth, endocrine and behavioural responses of male carp.

Use of 'Judas' fish to betray the locations of conspecifics is a powerful tool in management of invasive pest fish but poses a risk of contributing to recruitment. Our aim therefore was to generate surgically sterilised male common carp (Cyprinus carpio) and test whether they readily assimilate into wild populations, retain sexual behaviour and successfully betray the locations of feral carp. Male common carp were surgically sterilised (n=44) adopting a two-point nip technique, using either a haemoclip, suture or electro cautery to tie each of the testicular ducts about 2.5 cm cranial to urogenital sinus-retaining all of the glandular testis tissue. Observed survival (95%) and success (>70%) rates were relatively high. Plasma steroids (11-keto testosterone and 17ß-estradiol) were quantified by immunoassay. A subset of sterile and control male fish (n=7 each) were implanted with radio-transmitters and released into Lake Sorell (50 km(2)) and their ability to betray the location of feral carp was assessed by radio tracking and targeted fishing. There was a statistically significant difference in 11-keto testosterone and 17ß-estradiol levels over time (P<0.05), but not between the sterile and control groups within each sampling time (P>0.05), implying that surgery did not compromise the animals physiologically. The sterile Judas fish integrated well into the population-behaving similarly to control Judas males and assisted in the capture of feral carp. The study marks a significant breakthrough in the management of this pest fish with potential adoption to the management of other pest fish globally.

Pedestrian deaths in children--potential for prevention.

The National Paediatric Mortality Database was reviewed for the six year period 1st January 2006 to 31st December 2011 and all pedestrian deaths extracted, after review of available data the deaths were categorized as either traffic or non-traffic related. There were 45 child pedestrian fatalities in the period examined. Traffic related deaths accounted for 26 (58%) vs. 19 (42%) non-traffic related. Analysis of the deaths showed there was a male preponderance 28 (62%), weekend trend 22 (49%) with an evening 16 (35%) and summer peak 20 (44%). The highest proportion of deaths occurred in the 1-4 year age group 24 (53%), with 13 (28%) due to low speed vehicle rollovers, mainly occurring in residential driveways 8 (61%). Child pedestrian fatalities are highly preventable through the modification of risk factors including behavioural, social and environmental. Preventative action needs to be addressed, particularly in relation to non-traffic related deaths i.e, low speed vehicle rollovers.

New hazards in paediatric poisoning presentations.

Accidental ingestion is an important preventable cause of childhood morbidity. All accidental ingestion presentations (n = 478) to a tertiary paediatric ED from January 2010 to December 2011 were analysed. These results were compared with a similar study in the same institution ten years previously in 2001 and showed that while accidental ingestions constituted a higher proportion of presentations (0.5% in this study v 0.45% in 2001), fewer had investigations performed (21% v 35%) and fewer were admitted (7% v 20%). Accidental ingestions account for 0.5% of presentations and are an important focus of home safety information for parents and guardians. Paracetamol (n = 67, 14%) and liquid detergent capsules (n = 44, 9.2%) were the two most common substances implicated in these presentations, and have the potential to cause severe morbidity and mortality.

A Review of Clostridium difficile Infection at the University Hospital of the West Indies, Jamaica.

OBJECTIVES: This study examined the frequency of Clostridium difficile infection (CDI) among hospital admission and diarrhoeal stool samples over a six-year period. METHODS: A review of all suspected cases of C difficile positive patients from 2007 to 2012 at the University Hospital of the West Indies (UHWI), Jamaica, was performed. Clostridium difficile infection was confirmed by clinical features and a positive enzyme-linked immunosorbent assay (ELISA) stool test for Clostridium Toxins A and B. The demographics, clinical features, risk factors, treatment and outcomes were also examined. RESULTS: There were 56 patients reviewed. The most commonly affected age group was 40-59 years of age. The proportion of CDI cases per total stool samples increased from 0.5% in 2007 to 5.9% in 2010 then fell to 2.2% in 2011 but increased again to 4.3% in 2012. The proportion of cases per total UHWI admissions also increased from 0.12 cases per 1000 admissions in 2007 to 1.16 in 2010 and 1.36 in 2012 (p < 0.001). Most CDI cases were nosocomial (76% males, 48.6% females). Co-morbidities included hypertension and end-stage renal disease. Ceftazidime was the most common antibiotic associated with the development of CDI. Resolution occurred in 62.5% of patients. Duration of hospital stay was longer in males than females (≥ 21 versus < 7 days) and males had more adverse outcomes, with death in 23.8% versus 11.4%. CONCLUSION: There has been an increase in the frequency of CDI at UHWI with a greater than expected frequency of community acquired CDI. Increased awareness is needed of the increasing risk for CDI and measures must be taken to prevent the disease, especially in hospitalized patients.

Aminoglycoside Resistance in Clinical Isolates of Gram Negative Bacilli at the University Hospital of the West Indies, Jamaica: Comparison of Two Time Periods.

OBJECTIVE: Aminoglycosides were introduced into use over 60 years ago. The University Hospital of the West Indies (UHWI), a tertiary care teaching hospital, in Kingston, Jamaica, introduced the use of gentamicin in 1973 and amikacin in 1980. This report examined the susceptibility patterns to these agents in 1547 consecutive isolates of Gram negative bacilli (GNB) encountered between September 1 and November 30, 2011, at UHWI and compares the data with those observed previously in 1981 at the same institution. METHODS: The Vitek 2 (bioMeriéux, Durham, NC) was used for isolate identification, minimum inhibitory concentration determination and aminoglycoside susceptibility testing. Quality control was done using American Type Culture Collection standard strains of E coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). RESULTS: Of the 1547 organisms, 267 had resistance to one or both aminoglycosides. Amikacin resistance increased from 0.6% (1981) to 7.2% [2011] (p < 0.05), while gentamicin resistance increased from 6.7% to 14.8% (p < 0.05) for the corresponding period. The majority of samples with aminoglycoside resistant organisms came from the intensive care unit and surgical inpatients. Urine samples persistently produced the largest amount of gentamicin resistant isolates. CONCLUSIONS: Although there has been a statistically significant rise in aminoglycoside resistance, aminoglycosides continue to remain highly effective against approximately 83% of GNB despite continuous usage at this institution for over three decades. Continued national surveillance, implementation of infection control policies and antibiotic stewardship are all essential in retaining low resistance levels.

Systematic review and meta-analysis of enhanced recovery programmes in surgical patients.

BACKGROUND: Enhanced recovery programmes (ERPs) have been developed over the past 10 years to improve patient outcomes and to accelerate recovery after surgery. The existing literature focuses on specific specialties, mainly colorectal surgery. The aim of this review was to investigate whether the effect of ERPs on patient outcomes varies across surgical specialties or with the design of individual programmes. METHODS: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials were searched from inception to January 2013 for randomized or quasi-randomized trials comparing ERPs with standard care in adult elective surgical patients. RESULTS: Thirty-eight trials were included in the review, with a total of 5099 participants. Study design and quality was poor. Meta-analyses showed that ERPs reduced the primary length of stay (standardized mean difference -1·14 (95 per cent confidence interval -1·45 to -0·85)) and reduced the risk of all complications within 30 days (risk ratio (RR) 0·71, 95 per cent c.i. 0·60 to 0·86). There was no evidence of a reduction in mortality (RR 0·69, 95 per cent c.i. 0·34 to 1·39), major complications (RR 0·95, 0·69 to 1·31) or readmission rates (RR 0·96, 0·59 to 1·58). The impact of ERPs was similar across specialties and there was no consistent evidence that elements included within ERPs affected patient outcomes. CONCLUSION: ERPs are effective in reducing length of hospital stay and overall complication rates across surgical specialties. It was not possible to identify individual components that improved outcome. Qualitative synthesis may be more appropriate to investigate the determinants of success.