Poikilocytosis of Angora goats is associated with erythrocyte density and reticulocytosis.

Angora goats in South Africa experience several syndromes that result in notable morbidity and mortality in juveniles and adults, but not kids. Insight into their causes is hampered by the lack of normal reference values for this breed, and the present study therefore aimed to characterise (1) differences in the haematology of healthy kids at birth and weaning, and (2) the haematology of apparently healthy yearlings. Selected variables were measured by blood smear analysis, and complete blood counts were performed using an ADVIA 2120i. Variables at 1, 11, and 20 weeks of age were compared using the Friedman test and associations between variables of yearlings were determined by correlation analysis. In kids, red blood cell count, mean corpuscular haemoglobin concentration (MCHC), and poikilocytosis increased over time, while mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) decreased. Yearlings displayed a lower MCHC, and higher haemoglobin distribution width than previously reported for goats, and these were positively correlated with poikilocytosis, as were reticulocyte counts. White cell counts of yearlings exceeded normal values previously reported for goats, with some individuals displaying remarkably high mature neutrophil counts. Changes in haemoglobin variant expression or cation and water fluxes are possible explanations for the findings in kids, while in yearlings, the associations between MCHC, HDW, poikilocytosis, and reticulocytosis suggest alterations in red cell hydration in adulthood that are associated with increased red cell turnover. These findings may prove informative in the further investigation of various clinical syndromes in this population.

Adult life-course trajectories of psychological distress and economic outcomes in midlife during the COVID-19 pandemic: evidence from the 1958 and 1970 British birth cohorts.

PURPOSE: Financial adversity in times of economic recession have been shown to have an unequal effect on individuals with prior mental health problems. This study investigated the relationship between mental health groupings across the adult life-course and change in financial situation and employment status during the COVID-19 pandemic, as well as the use of financial measures to mitigate the economic shock. METHODS: Using two nationally representative British birth cohorts, the National Child Development Study (1958) n = 17,415 and 1970 British Cohort Study n = 17,198, we identified 5 different life-course trajectories of psychological distress from adolescence to midlife which were similar but not identical across the two cohorts. We explored their relation to changes in financial and employment circumstances at different stages during the pandemic from May 2020 to March 2021, applying multinomial logistic regression and controlling for numerous early life covariates, including family socio-economic status (SES). In addition, we ran modified Poisson models with robust standard errors to identify whether different mental health trajectories were supported by government and used other methods to mitigate their financial situation. RESULTS: We found that the financial circumstances of pre-pandemic trajectories of psychological distress with differential onset, severity, and chronicity across the life-course were exacerbated by the COVID-19 economic shock. The 'stable-high' (persistent severe symptoms) and 'adult-onset' (symptoms developing in 30s, but later decreasing) groups were vulnerable to job loss. Compared to pre-pandemic trajectory groupings with no, minor, or psychological distress symptoms in early adulthood, the 'stable-high', 'midlife-onset' (symptoms developing in midlife), and 'adult-onset' trajectory groups were more likely to seek support from the UK governments economic response package. However, trajectories with pre-pandemic psychological distress were also at greater risk of reducing consumption, dis-saving, relying on increased financial help from family and friends, and also taking payment holidays (agreements with lenders to pause mortgage, credit card or loan payments for a set period) and borrowing. CONCLUSION: This work highlights different trajectories of pre-pandemic psychological distress, compared to groups with no symptoms were more vulnerable to pandemic-related economic shock and job loss. By adopting unsustainable mitigating measures (borrowing and payment holidays) to support their financial circumstances during COVID-19, these mental health trajectories are at even more risk of lasting adverse impacts and future economic difficulties.

Effect of a milk byproduct-based calf starter feed on dairy calf nutrient consumption, rumen development, and performance when fed different milk levels.

The objective of this study was to investigate the effects of a milk byproduct-based starter pellet, high in lactose, on feed intakes, growth, and rumen development when calves were fed either a high or low level of milk. This was done by using a 2 × 2 factorial design, with 120 Holstein heifer calves randomly assigned to 1 of 2 milk treatments and 1 of 2 feed treatments upon enrollment at birth. Calves were either assigned to a low (LM) or high (HM) level of milk replacer by an automated milk-feeding system for individually-housed calves. The LM treatment calves were offered 6 L/d (150 g/L; 1.2 L, 5×/d), whereas HM treatment calves were offered 15 L/d (150 g/L; 3 L, 5×/d) of milk replacer. Calves were also assigned to a milk byproduct- (whey) based starter feed treatment (WF), or a grain-based starter ration (95% concentrate starter pellet, 5% chopped wheat straw) feed treatment (GF). All calves were offered their treatment feed starting on d 5, with water offered ad libitum from d 0. The WF treatment calves were offered 150 g/d of the milk byproduct-based pellet until they consumed the entirety for 2 out of 3 consecutive days. At this point, WF treatment calves received 150 g of the milk byproduct-based pellet top dressed onto the grain-based ration to allow for ad libitum feed consumption until weaned, when they only received the grain-based ration postweaning (d 64-77). Calves on the GF feed treatment received only the grain-based ration. All calves were gradually weaned from d 43 to 63. By design, calves on the HM treatment consumed greater levels of milk than LM treatment calves for the majority of the days in the preweaning phase (8.9 ± 0.11 vs. 5.5 ± 0.11 L/d; SE). Calves on the GF and WF treatments consumed similar amounts of milk in the preweaning phase (7.2 ± 0.11 vs. 7.2 ± 0.11 L/d); however, there was a milk and feed treatment interaction detected for milk consumption in the weaning phase, with HM-GF calves drinking more milk than the other treatments and HM-WF calves drinking more milk than both LM-GF and LM-WF calves. The WF treatment calves had greater solid feed intake during the preweaning phase than GF treatment calves, with no feed intake differences in the weaning or postweaning phases. The WF calves drank more water in the preweaning phase than GF calves. Average daily gain was similar throughout the study between the GF and WF treatment calves. Rumen physiological measures were all similar by the end of the trial (d 77) regardless of feed or milk treatment, suggesting similar rumen development postweaning. Overall, regardless of the level of milk fed, offering the milk byproduct-based starter pellet may increase preweaning feed intake, along with water consumption. However, both feed and milk treatments had similar performance and rumen development measures by the end of the trial.

Safe provision of elective endocrine surgery operations amid the COVID-19 crisis.

INTRODUCTION: The aim of this study was to determine the impact of the COVID-19 pandemic on the provision of clinical services (perioperative clinical outcomes and productivity) of the department of endocrine and general surgery at a teaching hospital in the UK. METHODS: A retrospective chart review was conducted of all patients who were operated in our department during two periods: 1 April to 31 October 2019 (pre-COVID-19 period) and 1 April to 31 October 2020 (COVID-19 period). The perioperative clinical outcomes and productivity of our department for the two time periods were compared. RESULTS: In the pre-COVID-19 period, 130 operations were carried out, whereas in the COVID-19 group, this reduced to 89. The baseline characteristics between the two groups did not significantly differ. Parathyroid operations decreased significantly by 68% between the two study periods. Overall, during the COVID-19 phase, the department maintained 68% of its operating workload compared with the respective 2019 time period. The clinical outcomes for the patients who had a thyroid/parathyroid/adrenal operation were not statistically different for the two study periods. There were no COVID-19 related perioperative complications for any of the operated patients and no patient tested positive for COVID-19 while an inpatient. For the COVID-19 group, the department maintained 67% of its outpatient appointments for endocrine surgery and 26% for general surgery pathologies. CONCLUSIONS: The COVID-19 pandemic significantly reduced the clinical activity of our department. However, it is possible to continue providing clinical services for urgent/cancer cases with the appropriate safety measures in place.

Evaluation of a lateral-flow nanoparticle fluorescence assay for TB infection diagnosis.

BACKGROUND: Programmatic management of TB infection is a critical component of the WHO End TB Strategy. Interferon-gamma release assays (IGRAs) overcome some limitations of the tuberculin skin test, but implementation of IGRA testing in low-resource settings is challenging.METHODS: In this feasibility study, we evaluated performance of a novel digital lateral-flow assay, the QIAreach® QuantiFERON® TB (QIAreach-QFT) test, against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay. A population with a mix of risk factors for TB infection (111 donors) were sampled over multiple days. A total of 207 individual blood samples were tested according to the manufacturer´s instructions.RESULTS: The overall percentage agreement was 95.6% (two-sided 95% CI 91.8-98), with a positive percentage agreement (i.e., sensitivity) of 100% (95% CI 94.7-100) and a negative percentage agreement (i.e., specificity) of 95.6% (95% CI 90.6-98.4). All QFT-Plus positive specimens with TB1-Nil and TB2-Nil values less than 1 IU/ml tested positive on QIAreach-QFT.CONCLUSIONS: QIAreach QFT is a deployable, accurate testing solution for decentralised testing. It has the potential to overcome key hurdles for TB infection screening in high-burden settings thus helping to achieve the WHO End TB programme goals.

Effects of delaying increase in milk allowance and type of gradual weaning program on performance and health of calves fed lower levels of milk.

The objective of this study was to investigate the effects of delayed increase in milk allowance and type of gradual weaning program on the feed intake, health, and growth of male Holstein calves. Using a 2 × 2 factorial design, each male Holstein calf was randomly assigned to 1 of 2 milk level treatments and 1 of 2 weaning treatments upon arrival to a rearing facility. Calves were either assigned to a moderate (MM) or lower (LM) milk level treatment. All calves received the same milk program from arrival until d 12, increasing from 4 to 5 L/d (115 to 125 g/L) over the 12 d. On d 13, MM calves began receiving additional milk compared with LM calves until they were weaned, with MM offered milk increasing to a peak of 9 L/d (140 g/L). Calves on the MM treatment received a total of 35 kg of milk replacer over 45 d, compared with LM calves, who received a total of 25 kg of milk replacer over 45 d. Calves were also assigned to be weaned by either a 2-step gradual program or a 4-step gradual program. Calves assigned to the 2-step program had their milk reduced in 2 steps from d 30 to 45, and 4-step calves had their milk reduced in 4 steps from d 30 to 45. After d 46, calves received no milk but continued to be monitored until d 59. Calves had ad libitum access to water from arrival, and solid feed was offered from d 5 onward. No interactions of effects of milk level and weaning treatment were detected. By design, calves on the MM treatment consumed greater amounts of milk than LM calves in the preweaning phase from d 13 to 29 (6.1 vs. 4.8 L/d) and weaning phases from d 30 to 45 (4.7 vs. 3.2 L/d). The LM calves consumed greater amounts of solid feed than MM calves from d 22 to 29 of the preweaning phase, and from d 30 to 40 and d 43 to 45 of the weaning phase, whereas postweaning feed consumption was similar for both milk treatments. Calves in both milk treatments had similar blood ß-hydroxybutyrate levels, indicating similar rumen development. Body weight and size measurements were similar between milk treatments across the study, although LM calves had a greater average daily gain than MM calves between d 38 and 46 (0.96 vs. 0.71 kg/d). Both gradual weaning treatments resulted in similar feed consumption, growth, and health parameters. Overall, the results indicate that delaying a moderate increase in milk until 12 d after arrival at a rearing facility provided no overall beneficial effect on growth or rumen development.

Investigation of weaning strategy and solid feed location for dairy calves individually fed with an automated milk feeding system.

The objective of this study was to investigate the effect of 2 gradual weaning programs and 2 locations of solid feed within individual calf pens on feed intake, growth, and behavior of calves fed milk by an automated milk feeder. Using a 2 × 2 factorial design, 60 female calves were randomly assigned to 1 of 2 weaning treatments and 1 of 2 solid feed placement treatments. Calves were assigned to a continuous gradual weaning program (CG) or a multi-step gradual weaning program (MG). Calves assigned to the CG treatment had their milk allocation reduced in small, equal increments from 12.5 L/d on d 43 to 2 L/d on d 56. Calves assigned to the MG treatment were offered 10 L/d on d 43 to 45, 8 L/d on d 46 to 49, 6 L/d on d 50 to 52, and 3 L/d on d 53 to 56. Solid feed was placed either at the front of the pen adjacent (ADJ) to where the automated milk feeder offered milk or at the back of the pen on the opposite (OPP) side from where the milk was offered. All calves were offered 12.5 L/d of milk replacer from d 2 to 42, fresh solid feed (5% chopped wheat straw mixed with 95% calf starter pellet) from d 5 onward, and ad libitum water starting d 0. Calves were weaned from d 43 to 56 and additionally monitored from d 57 to 70. No interactions of effects of weaning and feed location treatment were detected. Both MG and CG calves had similar water and solid feed consumption, blood ß-hydroxybutyrate concentrations, and behavior. By design, calves on the CG treatment consumed greater amounts of milk during the weaning phase than MG treatment calves (6.7 vs. 6.3 L/d), which resulted in milk drinking behavior differing between the treatments during the weaning phase. Although average daily gain and body weights were similar between treatments, MG calves had greater middle girth gain during wk 7 compared with CG calves (0.6 vs. 0.3 cm/d). Calves on the ADJ treatment consumed 16.7% more solid feed and 0.55 L/d more milk during the preweaning phase compared with OPP treatment calves. In all 3 phases, ADJ treatment calves consumed more water than OPP treatment calves. The ADJ calves spent more time consuming solid feed during the 10-wk period. The ADJ treatment calves had 10% greater average daily gain compared with OPP treatment calves during the preweaning phase. Overall, the results indicate that both gradual weaning treatments resulted in similar performance and behavior. However, placement of solid feed next to the milk source was demonstrated to increase feed, water, and milk intake during the preweaning stage, contributing to greater growth.

Influence of granular activated carbon media properties on natural organic matter and disinfection by-product precursor removal from drinking water.

Operational and financial constraints challenge effective removal of natural organic matter (NOM), and specifically disinfection by-product (DBP) precursors, at remote and/or small sites. Granular activated carbon (GAC) is a widely used treatment option for such locations, due to its relatively low maintenance and process operational simplicity. However, its efficacy is highly dependent on the media capacity for the organic matter, which in turn depends on the media characteristics. The influence of GAC media properties on NOM/DBP precursor removal has been studied using a range of established and emerging media using both batch adsorption tests and rapid small-scale column tests. DBP formation propensity (DBPFP) was measured with reference to trihalomethanes (THMs) and haloacetic acids (HAAs). All GAC media showed no selectivity for specific removal of precursors of regulated DBPs; DBP formation was a simple function of residual dissolved organic carbon (DOC) levels. UV254 was found to be a good surrogate measurement of DBPFP for an untreated water source having a high DOC. Due to the much-reduced concentration of DBP precursors, the correlation was significantly poorer for the coagulation/flocculation-pretreateed water source. Breakthrough curves generated from the microcolumn trials revealed DOC removal and consequent DBP reduction to correlate reasonably well with the prevalence pores in the 5-10 nm range. A 3-6 fold increase in capacity was recorded for a 0.005-0.045 cm3/g change in 5-10 nm-sized pore volume density. No corresponding correlation was evident with other media pore size ranges.

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study.

BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference -0·83 (95 per cent c.i. -1·4 to -0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

ANTECEDENTES: Las estatinas inhiben las señalizaciones proliferativas en el adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC) y su uso se asocia con mejor supervivencia en estudios observacionales. El presente estudio se llevó a cabo para examinar la viabilidad de evaluar el tratamiento adyuvante con estatinas en pacientes con OAC operable en un ensayo aleatorizado y controlado de fase III. MÉTODOS: En este ensayo de viabilidad controlado por placebo, aleatorizado, de grupos paralelos, doble ciego y multicéntrico, los pacientes adultos con OAC (incluyendo lesiones Siewert I/II) que fueron sometidos a esofaguectomía se asignaron de forma centralizada (1:1) a tratamiento con simvastatina 40 mg o placebo equivalente mediante aleatorización en bloques, estratificados por centro. Los participantes, los clínicos y los investigadores desconocían la asignación del tratamiento. Los pacientes recibieron el tratamiento hasta un año. Los resultados de viabilidad fueron reclutamiento, retención, absorción del fármaco, adherencia, seguridad, calidad de vida, generalización, y supervivencia. RESULTADOS: Un total de 120 pacientes fueron evaluados para elegibilidad en 4 centros, de los cuales 32 (26,7%) fueron aleatorizados, 16 en cada grupo. Siete pacientes abandonaron el ensayo. Los pacientes asignados a tratamiento con simvastatina tenían niveles de colesterol LDL más bajos a los 3 meses (diferencia media ajustada, −0,83 mmol/L, i.c. del 95% −1,4 a −0,22, P = 0,009). La mediana de la adherencia a la medicación fue mayor del 90% entre los 3-12 meses de seguimiento. Los eventos adversos fueron similares entre los grupos. Los datos de calidad de vida estaban completos en el 98,3% de las preguntas del cuestionario. Enfermedad cardiovascular, diabetes y uso de aspirina eran más prevalentes en el grupo no aleatorizado, mientras que la localización del tumor, el estadio y el grado fueron similares entre los grupos. Las estimaciones de supervivencia fueron imprecisas. CONCLUSIÓN: Este RCT apoya la realización e informa de las consideraciones de diseño para un futuro ensayo de fase III de tratamiento adyuvante con estatinas en pacientes con OAC.

Machine learning to predict early recurrence after oesophageal cancer surgery.

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.

Impact of postoperative complications on disease recurrence and long-term survival following oesophagogastric cancer resection.

BACKGROUND: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear. METHODS: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination. RESULTS: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival. CONCLUSION: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival.

Effect of structured self-monitoring of blood glucose, with and without additional TeleCare support, on overall glycaemic control in non-insulin treated Type 2 diabetes: the SMBG Study, a 12-month randomized controlled trial.

AIM: To examine the impact of structured self-monitoring of blood glucose, with or without TeleCare support, on glycaemic control in people with sub-optimally controlled Type 2 diabetes. METHODS: We conducted a 12-month, multicentre, randomized controlled trial in people with established (>1 year) Type 2 diabetes not on insulin therapy, with sub-optimal glycaemic control [HbA1c ≥58 to ≤119 mmol/mol (≥7.5% to ≤13%)]. A total of 446 participants were randomized to a control group (n =151) receiving usual diabetes care, a group using structured self-monitoring of blood glucose alone (n =147) or a group using structured self-monitoring of blood glucose with additional monthly 'TeleCare' support (n =148). The primary outcome was HbA1c at 12 months. RESULTS: A total of 323 participants (72%) completed the study; 116 (77%) in the control group, 99 (67%) in the self-monitoring of blood glucose alone group and 108 (73%) in the self-monitoring of blood glucose plus TeleCare group. Compared to baseline, the mean HbA1c was lower in all groups at 12 months, with reductions of 3.3 mmol/mol (95% CI -5.71 to -0.78) or 0.3% (95% CI -0.52 to -0.07; P=0.01) in the control group, 11.4 mmol/mol (95% CI -14.11 to -8.76) or 1.1% (-1.29 to -0.81; P<0.0001) in the group using self-monitoring of blood glucose alone and 12.8 mmol/mol (95% CI -15.34 to -10.31) or 1.2% (95% CI -1.40 to -0.94; P<0.0001) in the group using self-monitoring of blood glucose plus TeleCare. This represents a reduction in HbA1c of 8.9 mmol/mol (95% CI -11.97 to -5.84) or 0.8% (95% CI -1.10 to -0.54; P≤0.0001) with structured self-monitoring of blood glucose compared to the control group. Participants with lower baseline HbA1c , shorter duration of diabetes and higher educational achievement were more likely to achieve HbA1c ≤53 mmol/mol (7.0%). CONCLUSIONS: Structured self-monitoring of blood glucose provides clinical and statistical improvements in glycaemic control in Type 2 diabetes. No additional benefit, over and above the use of structured self-monitoring of blood glucose, was observed in glycaemic control with the addition of once-monthly TeleCare support. (Clinical trial registration no.: ISRCTN21390608).

Antigen-specific interferon-gamma release is decreased following the single intradermal comparative cervical skin test in African buffaloes (Syncerus caffer).

Effective disease management of wildlife relies on the strategic application of ante-mortem diagnostic tests for early identification and removal of M. bovis-infected animals. To improve diagnostic performance, interferon-gamma release assays (IGRAs) are often used in conjunction with the tuberculin skin test (TST). Since buffaloes are major maintenance hosts of M. bovis, optimal application of bovine TB diagnostic tests are especially important. We aimed to determine whether the timing of blood collection relative to the TST has an influence on IFN-γ production and diagnostic outcome in African buffaloes. Release of IFN-γ in response to bovine purified protein derivative (PPD), avian PPD and PC-HP® and PC-EC® peptides was measured by Bovigam® and an in-house IGRA in a group of Bovigam®-positive and - negative buffaloes at the time the TST was performed and three days later. There was significantly lower IFN-γ release in response to these antigens post-TST in Bovigam®-positive buffaloes, but no significant changes in Bovigam®-negative buffaloes. Also, a significantly greater proportion of buffaloes were Bovigam®-positive prior to the TST than three days later. We therefore recommend that blood samples for use in IGRAs be collected prior to or at the time the TST is performed to facilitate the correct identification of greater numbers of IGRA-positive buffaloes.

Seroprevalence of Mycobacterium bovis infection in warthogs (Phacochoerus africanus) in bovine tuberculosis-endemic regions of South Africa.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis (M. bovis), has been reported in many species including suids. Wild boar are important maintenance hosts of the infection with other suids, that is domestic and feral pigs, being important spillover hosts in the Eurasian ecosystem and in South Africa, warthogs (Phacochoerus africanus) may play a similar role in M. bovis-endemic areas. However, novel diagnostic tests for warthogs are required to investigate the epidemiology of bTB in this species. Recent studies have demonstrated that serological assays are capable of discriminating between M. bovis-infected and uninfected warthogs (Roos et al., ). In this study, an indirect ELISA utilizing M. bovis purified protein derivative (PPD) as a test antigen was used to measure the prevalence and investigate risk factors associated with infection in warthogs from uMhkuze Nature Reserve and the southern region of the Greater Kruger National Park (GKNP). There was a high overall seroprevalence of 38%, with adult warthogs having a higher risk of infection (46%). Seroprevalence also varied by geographic location with warthogs from Marloth Park in the GKNP having the greatest percentage of positive animals (63%). This study indicates that warthogs in M. bovis-endemic areas are at high risk of becoming infected with mycobacteria. Warthogs might present an under-recognized disease threat in multi-species systems. They might also serve as convenient sentinels for M. bovis in endemic areas. These findings highlight the importance of epidemiological studies in wildlife to understand the role each species plays in disease ecology.

Arthroscopic subtalar arthrodesis through the sinus tarsi portal approach: A series of 77 cases.

BACKGROUND: Subtalar arthrodesis through an open approach carries significant risk of complications. An arthroscopic approach aims to minimise damage to the soft tissue envelope to improve recovery, union and complication rates. A two portal approach through the sinus tarsi was used. METHODS: A retrospective review of all patients undergoing isolated arthroscopic arthrodesis was performed. RESULTS: Seventy-seven procedures were performed. Successful arthrodesis was achieved in 75 (97.4%). Two patients underwent successful revision arthrodesis for aseptic nonunion. There was one (1.3%) superficial infection and one (1.3%) partial sural nerve injury. CONCLUSIONS: Two-portal sinus tarsi arthroscopic subtalar arthrodesis is safe and effective. Advantages over other arthroscopic approaches are the access to all three facets of the joint, avoidance of a posterolateral portal in order to minimise risk to the sural nerve, and the ability to use the same approach to arthrodese the entire triple hindfoot joint complex. Technical tips and pitfalls are discussed.

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.