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Suboptimal status of folate and/or interrelated B vitamins (B12, B6 and riboflavin) can perturb one‐carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate‐related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence‐based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition–epigenome–brain relationship, particularly focussing on folate‐related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio‐banked samples from existing well‐characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition–epigenome–brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state‐of‐the‐art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle. [ABSTRACT FROM AUTHOR]

Instrumental weather records (1880–2020s) from eastern North America were analyzed to characterize the regional patterns and drivers of seasonal extreme weather (snow, rain, high and low temperatures). Using agglomerative hierarchical clustering of extreme weather data, the region was divided into three subregions that are influenced by coastal‐marine gradients and latitudinal factors. Subsequent analyses were performed on high‐quality stations from each subregion and results compared between one another. Long‐term locally weighted linear regressions delineated long‐term changes in extreme weather, and a combination of spectral analysis, continuous wavelet transforms, and cross wavelet transforms were used to identify periodic components in the data. Regional extreme weather is generally periodic, composed of interannual to interdecadal‐scale oscillations and driven by several natural climatic oscillations. The most important such oscillation is the 11‐year Schwabe Solar Cycle, which has a strong and continuous effect on regional extreme weather. The Pacific Decadal Oscillation and Quasi Biennial Oscillation also show considerable influence, but intermittently. The El Niño Southern Oscillation, the Arctic Oscillation, and the North Atlantic Oscillation all have a weaker but interrelated influence. While the Atlantic Multidecadal Oscillation showed the weakest overall influence on regional extreme weather, it demonstrated a clear spatial gradient across the region, unlike the aforementioned oscillations. Long‐term changes in regional extreme weather are not generally important, in that a sustained increase or decrease in extreme weather events is not usually characteristic of the weather records. The primary exception to this result is for extreme minimum temperature events, whose frequency has slightly decreased since the 1880s. Key Points: Extreme weather events across eastern North America from 1881 to 2020 were analyzed for trends and patternsEastern North America exhibits three distinct extreme weather subregionsCyclic patterns in extreme weather were attributed to various large‐scale climate oscillations [ABSTRACT FROM AUTHOR]

Aim: A 'watch and wait' (W&W) strategy after neoadjuvant long‐course chemoradiotherapy (NACRT) remains controversial. Whilst encouraging short‐term data exist, the strategy will be judged on long‐term data. We present long‐term, real‐world UK data from a single National Health Service trust. Methods: An analysis was performed of a prospectively maintained W&W database over 9 years between 2010 and 2018. Outcome measures include incidence and time to regrowth and overall and disease‐free survival. Results: We diagnosed 563 rectal cancers in 9 years. In all, 283 patients underwent rectal resection (50.3%). NACRT was used in 155 patients for margin‐threatened tumours on staging MRI. Forty‐nine patients (31.6%) experienced either a 'near complete' or a complete clinical response (cCR) at their 10 weeks post‐NACRT assessment (MRI and endoscopy). The median age was 69 years (range 44–83), and the male to female ratio was 32:17. The median follow‐up was 38 months (range 12–96). The median tumour distance from the anal verge was 7 cm (1–15 cm). Twenty‐two patients had a cCR on initial assessment and 27 patients had a 'near' cCR. Of those 27 who experienced a 'near' cCR, 17 (63%) progressed to cCR on repeat assessment and 10 (37%) did not. Of these 10 patients, seven underwent standard surgical resection and three were unfit for surgery. R0 for the seven with delayed resection was 100%. Of 39 patients (22 cCR and 17 'near' cCR who progressed to cCR) (25.2% of those receiving NACRT), six patients experienced local regrowth (15.4%). The median time to local regrowth was 29 months (15–60 months). One of these six patients underwent salvage abdominoperineal resection, one was advised to have contact radiotherapy and four opted against surgery and also had contact radiotherapy. The overall survival was 100% at 2 years and 90% at 5 years. Disease‐free survival was 90.47% at 2 years and 74.8% at 5 years. Conclusion: A W&W treatment strategy was employed safely in this patient cohort with acceptable rates of local regrowth and survival. [ABSTRACT FROM AUTHOR]

Keywords: Ileoanal pouch; outcomes; rectal cancer; total mesorectal excision; transanal EN Ileoanal pouch outcomes rectal cancer total mesorectal excision transanal 745 748 4 07/27/20 20200701 NES 200701 The Association of Coloproctology of Great Britain and Ireland (ACPGBI) has noted with concern the results of transanal total mesorectal excision (TME) procedures reported by the Norwegian Colorectal Cancer Registry, recently published in the I British Journal of Surgery i [1]. Short-term outcomes from the International Transanal TME registry were reported on 2653 patients undergoing a transanal TME approach for rectal cancer between 2014 and 2018 [12]. The annual institutional caseload of 25 transanal TME procedures is set at the lower limit of the 25 to >40 transanal rectal cancer resections recommended by the latest international transanal TME consensus, to which the ACPGBI contributed (R. Hompes, pers.comm.). [Extracted from the article]

Irrespective of data quality, arguments against the routine introduction of MOAB prior to elective bowel resection centre around the fact that SSI reduction bundles alone can achieve low rates of SSI without necessarily including MOAB. However, the inclusion of both colon and rectal resections together introduces heterogeneity and possible difficulty with interpretation as OAB alone may be preferred in colonic surgery and MOAB in rectal surgery [93]. Comparing mechanical bowel preparation with both oral and systemic antibiotics versus mechanical bowel preparation and systemic antibiotics alone for the prevention of surgical site infection after elective colorectal surgery: a meta-analysis of randomized controlled clinical trials. Meta-analysis of oral antibiotics, in combination with preoperative intravenous antibiotics and mechanical bowel preparation the day before surgery, compared with intravenous antibiotics and mechanical bowel preparation alone to reduce surgical-site infections in elective colorectal surgery. [Extracted from the article]

Background: Although in the last decade some research has emerged on temperament in autism spectrum disorder (ASD), this research has primarily focused on the differences between children with ASD and their typically developing peers rather than the stability or change in temperament in this population. Thus, the goal of this study was to examine temperament over time in children with ASD, developmental delays (DD) and typical development (TD). Temperament differences were also compared among the three groups. Methods: To accomplish this, parents rated children's temperament at Time 1 (T1) and Time 2 (T2) using the Carey Temperament Scales (CTS). Results: Results from the study showed that at T1, parents of children with ASD rated their children as more withdrawn (i.e. approach), and emotionally negative (i.e. mood), and less distractible and adaptable than parents of children with TD and DD. Also, children with ASD were rated as more intense and children with DD as less distractible than their TD peers. Similarly, at T2, children with ASD were rated more withdrawn, and emotionally negative, and less persistent, rhythmic, adaptable and distractible than children with TD and DD. Also, children with ASD were rated as more active than their DD peers. Regarding stability, parent ratings of temperament appeared stable over time in the TD group, but ratings varied substantially in the ASD or DD groups. That is, for the ASD group, activity and approach at T1 were significantly associated with their corresponding dimensions at T2. However, for the TD group, rhythmicity, approach, intensity and mood at T1 were significantly associated with those dimensions at T2. No associations were found in the DD group. Regarding change, parents reported change in rhythmicity, persistence and threshold between T1 and T2 in the ASD group. Similarly, parents reported change in rhythmicity, approach and threshold between T1 and T2 in the DD group. Lastly, parents of TD children reported change in adaptability, persistence and distractibility between T1 and T2. Conclusions: These findings are novel in that children with ASD appear to have less stable temperament profile and different change patterns than children with TD or DD. Similar to previous research, children with ASD were described by their parents as experiencing more temperamental difficulties. [ABSTRACT FROM AUTHOR]

Aim: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. Methods: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. Results: All aspects of surgical care for IBD have been included along with 157 recommendations for management. Conclusion: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery. [ABSTRACT FROM AUTHOR]

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra‐axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335‐associated microcephaly. [ABSTRACT FROM AUTHOR]

Abstract: Southeast Asia experiences frequent fires in fuel‐rich tropical peatlands, leading to extreme episodes of regional haze with high concentrations of fine particulate matter (PM2.5) impacting human health. In a study published recently, the first field measurements of PM2.5 emission factors for tropical peat fires showed larger emissions than from other fuel types. Here we report even higher PM2.5 emission factors, measured at newly ignited peat fires in Malaysia, suggesting that current estimates of fine particulate emissions from peat fires may be underestimated by a factor of 3 or more. In addition, we use both field and laboratory measurements of burning peat to provide the first mechanistic explanation for the high variability in PM2.5 emission factors, demonstrating that buildup of a surface ash layer causes the emissions of PM2.5 to decrease as the peat fire progresses. This finding implies that peat fires are more hazardous (in terms of aerosol emissions) when first ignited than when still burning many days later. Varying emission factors for PM2.5 also have implications for our ability to correctly model the climate and air quality impacts downwind of the peat fires. For modelers able to implement a time‐varying emission factor, we recommend an emission factor for PM2.5 from newly ignited tropical peat fires of 58 g of PM2.5 per kilogram of dry fuel consumed (g/kg), reducing exponentially at a rate of 9%/day. If the age of the fire is unknown or only a single value may be used, we recommend an average value of 24 g/kg. [ABSTRACT FROM AUTHOR]

Background While there is substantial literature addressing the principles of general management of haemophilia, literature on perioperative management of haemostasis is scarce. Objective The aim of this study was to better understand perioperative management among congenital haemophilia B patients (without inhibitors) and to gain insights into real-world surgical practices. Method A systematic literature review, with an emphasis on haemophilia B, was conducted using EMBASE®, Medline® and the Cochrane Library. Studies from 1974 to June 2015 were accessed, and 132 studies were eligible for the full-study review. An international expert panel with five haematologists and one surgeon reviewed the resulting literature and provided further insights. Results The literature review revealed that documented experience in the perioperative management of bleeding risk in haemophilia B patients is relatively scarce. Therefore, the review was amended to provide a comprehensive overview of the perioperative management for haemophilia A and B patients; the expert panel applied a particular focus to haemophilia B. Several gaps were identified in the literature including the lack of consensus on defining surgery in terms of bleeding risk, optimal factor levels during surgery and lack of robust evidence on surgical outcomes. The ensuing discussions with the expert panel provided validation of some of the results from the systematic literature review and proposed future directions for perioperative management. Suggestions included collaboration with haemophilia treatment centres ( HTCs) to collect real-world data on perioperative management, establishing the need for optimal factor level monitoring practice, and the appropriate adoption of extended half-life products in clinical settings. [ABSTRACT FROM AUTHOR]

In this article, the author reflects on the article published within the issue on efficacy of the numerous supraglottic airway devices (SAD) for paediatric anaesthesia and benefits of meta-analysis. It mentions guidance of the National Institute for Health and Care Excellence (NICE) Decision Support Unit in carrying out their analysis and associated consistency checks and sensitivity analyses. It also mentions health technology assessments and drug re-imbursement decisions.

Objective: To report the response to progestin therapy in young women with endometrial complex atypical hyperplasia (CAH) or FIGO grade 1 endometrial adenocarcinoma (FIGO 1 EAC) based on clinicopathologic features, including abnormal DNA mismatch repair (MMR) by immunohistochemistry (IHC).Design: Consecutive case series.Setting: Olive View-UCLA Medical Center in Sylmar, CA, USA, and Cedars-Sinai Medical Center in Los Angeles, CA, USA.Population: Women ≤55 years old with CAH or FIGO 1 EAC.Methods: Response to progestin therapy in 84 consecutive patients was assessed based on clinicopathologic factors, including age, body mass index (BMI), initial histology, and IHC staining for MMR proteins.Main Outcome Measures: Rates of abnormal MMR protein expression and response to progestin therapy were determined.Results: Six (7%) patients had abnormal IHC staining, of whom five (83%) had FIGO 1 EAC at initial diagnosis. Following progestin treatment, none of the endometrial lesions in patients with abnormal IHC for MMR proteins had resolution of hyperplasia or malignancy, in contrast to 41 (53%) with normal staining (P = 0.028). Age ≤40 years and initial lesion (CAH versus FIGO 1 EAC) were predictors of response to progestin; BMI was not.Conclusions: In this cohort, 7% of women ≤55 years of age with CAH or FIGO 1 EAC had loss of MMR proteins by IHC. These patients had a higher incidence of invasive cancer and a lower incidence of resolution with progestin therapy.Tweetable Abstract: Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC. [ABSTRACT FROM AUTHOR]

Introduction Chronic hepatitis C virus ( HCV) infection is prevalent among patients with inherited bleeding disorders and is a leading cause of mortality in those with haemophilia. Aim We evaluated the efficacy and safety of ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic HCV genotype 1-4 infection and an inherited bleeding disorder. Methods Ledipasvir-sofosbuvir was administered for 12 weeks to patients with genotype 1 or 4 infection and for 12 or 24 weeks to treatment-experienced cirrhotic patients with genotype 1 infection. Patients with genotype 2 and 3 infection received sofosbuvir plus ribavirin for 12 and 24 weeks respectively. Results The majority of the 120 treated patients had a severe bleeding disorder (55%); overall, 65% of patients had haemophilia A and 26% of patients had haemophilia B; 22% were HIV coinfected. Sustained virologic response at 12 weeks posttreatment was 99% (98/99) in patients with genotype 1 or 4 infection; 100% (5/5) in treatment-experienced cirrhotic patients with genotype 1 infection; 100% (10/10) in patients with genotype 2 infection; and 83% (5/6) in patients with genotype 3 infection. There were no treatment discontinuations due to adverse events ( AEs). The most frequent non-bleeding AEs were fatigue, headache, diarrhoea, nausea and insomnia. Bleeding AEs occurred in 22 patients, of which all but one were considered unrelated to treatment. Conclusion Treatment with ledipasvir-sofosbuvir for patients with HCV genotype 1 or 4 infection or sofosbuvir plus ribavirin for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders. [ABSTRACT FROM AUTHOR]

Aim The ratio of positive nodes to total nodes, the lymph node ratio ( LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. Method Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. Results The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort ( n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). Conclusion Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point. [ABSTRACT FROM AUTHOR]

Background Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. Aim To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. Methods Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. Results On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4−19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. Conclusions The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder. [ABSTRACT FROM AUTHOR]

Introduction Development of inhibitors to human FVIII ( hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A. Aim This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r- pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors. Methods Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL−1 were treated with 50 U kg−1 body weight r- pFVIII. Those with pFVIII inhibitor titres of >0.8 BU mL−1 received an initial calculated r- pFVIII loading dose followed by 50 U kg−1 treatment dose. Treatment continued at 6-hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached. Results All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14-34 years) were controlled successfully with eight or fewer injections of r- pFVIII. The median time from bleeding onset to the administration of r- pFVIII was 5.7 h (range: 1.5-20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r- pFVIII (with or without a loading dose, median dose: 200.8 U kg−1; range: 50-576 U kg−1) regardless of pFVIII level. r- pFVIII was well tolerated and no treatment-emergent serious adverse events were considered by the investigator to be related to r- pFVIII administration. Conclusion The results suggest that FVIII replacement therapy with r- pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors. [ABSTRACT FROM AUTHOR]

Background Airway inflammatory phenotyping is increasingly applied to subjects with asthma. However, its relationship to clinical outcomes in difficult asthma is incompletely elucidated. Objective The goal of our study was to determine the relationship between exacerbation rates and phenotypes of difficult asthma based on the longitudinal measures of sputum eosinophils and neutrophils. Methods Subjects in the longitudinal observational study from two tertiary care centres that completed 1 year of observation and provided at least three sputum samples were classified by inflammatory phenotypes using previously established thresholds. Kaplan-Meier curves and univariable and multivariable Cox proportional hazard models were used to determine the association between inflammatory phenotypes and exacerbation rate. Results During the study, 115 exacerbations occurred in 73 severe asthmatic subjects. Subjects with the persistently eosinophilic phenotype had a significantly shorter time to first exacerbation and greater risk of exacerbation over a 1-year period than those with the non-eosinophilic phenotype based on the univariable and multivariable Cox proportional hazard model (hazard ratio [ HR], 3.24; 95% confidence interval [ CI], 1.35-7.72; adjusted HR, 3.90; 95% CI, 1.34-11.36). No significant differences in time to first exacerbation or exacerbation risk over a 1-year period were observed among the neutrophilic phenotypes. Conclusions The persistent eosinophilic phenotype is associated with increased exacerbation risk compared with the non-eosinophilic phenotype in severe asthma. No differences in time to first exacerbation or exacerbation risk over a 1-year period were detected among neutrophilic phenotypes. [ABSTRACT FROM AUTHOR]

Background The paradigm™2 and 4 phase 3 clinical trials investigated the safety and efficacy of nonacog beta pegol, a recombinant glyco PEGylated factor IX ( FIX) with extended half-life, in previously treated haemophilia B patients. Aim These post hoc analyses investigated the bleeding patterns in target joints. Methods Patients randomized to 40 or 10 IU kg−1 once weekly prophylaxis who had at least one target joint were included. Baseline demographics and disease-specific data were collected. Bleeding patterns were assessed, and an International Society on Thrombosis and Haemostasis ( ISTH) definition of target joints was used. Results A total of 67% and 8% of patients in the 40 and 10 IU kg−1 arm, respectively, did not experience target joint bleeds during the paradigm™2 trial. Twenty-four target joints were recorded in each prophylaxis arm at baseline. During the paradigm™2 trial, no bleeds were reported in 17 (71%) and 7 (29%) target joints in the 40 and 10 IU kg−1 arms respectively. All target joint bleeds in the 40 IU kg−1 once weekly prophylaxis arm were controlled with a single injection of 40 IU kg−1 nonacog beta pegol. By the latest ISTH definition, 90% and 58% of target joints in the 40 and 10 IU kg−1 arms, respectively, were no longer considered target joints at the end of the paradigm™2 trial. At the end of the paradigm™4 extension trial, all target joints in the 40 IU kg−1 arm were no longer considered target joints. Conclusion Routine prophylaxis with 40 IU kg−1 once weekly nonacog beta pegol has the potential for effective management of target joint bleeds in haemophilia B patients. [ABSTRACT FROM AUTHOR]

Reasons for performing study More knowledge of equine influenza ( EI) vaccine usage in training yards and the factors that influence serological response to vaccination are required to determine evidence-based vaccination strategies. Objectives The aim of this study was to ascertain the vaccination history of a population of Thoroughbred racehorses and identify factors that impacted on their antibody titres against EI. Study design Observational field study. Methods The study population consisted of 102 vaccinated Thoroughbred horses in training on a single premises. The vaccination histories recorded in their official passports were analysed. Blood samples for serological testing were collected by the veterinary surgeon one month after booster vaccination with Proteq Flu- Te. Antibodies against EI were measured by single radial haemolysis ( SRH). Multivariate statistical analysis was undertaken to determine the predictors of SRH antibody titres. Results There was a strong correlation between age and number of vaccine doses received. Over 70% of horses received their first vaccine dose between ages 6 and 12 months. On average, horses had received 6 vaccine doses and the mean interval between booster vaccinations was 7.7 months. The majority of horses (95%) received more than one influenza vaccine product while 32% had received 3 vaccine products. Significantly higher antibody levels were observed in females than males and there was a significant association between the number of vaccine products administered and antibody levels. In contrast, a negative association between number of vaccine doses and SRH antibody level was demonstrated. Conclusions Important predictors of EI antibody titres in racehorses were sex, number of vaccine doses received and number of different vaccine products administered. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Partial monochorionic and monoamniotic twin pregnancies: a report of two cases," by S. Galjaard and colleagues in the 2014 issue.

Despite benefits to crop rotations and recent increases in value, the United States produces only a third of the canola (Brassica napus L.) it consumes. To encourage production expansion, an experiment in Moscow, ID, evaluated dual-purpose winter canola in a biennial system for forage and seed production. Two winter canola cultivars were sown at three planting densities (4.5, 6.7, and 9.0 kg ha-1) over four planting dates (May through September) in 2008, 2009, 2010, and 2011. Vegetative biomass during the first year was harvested and ensiled to determine silage quality. Cultivars performed similarly over all treatments for forage yield and quality. The two highest planting densities yielded more forage, but no seed yield differences were detected. Total dry matter forage yield (DMFY) was greatest for May plantings (5.2 t DM ha-1), while August seeded canola yielded 2.4 t DM ha-1. Baldur produced higher seed yield than Athena by 352 kg ha-1, while planting dates had significant, but inconsistent effects on seed yield compared to the fall-planted, uncut control, which averaged 2389 kg ha-1. Fiber content of canola silage (canolage) was extremely low while crude protein (CP) remained consistently high. Canolage quality was exceedingly high, however, high silage pH indicated poor ensiling, which likely led to excessive loss of organic material in the silage that increased ash content. Early-planted winter canola withstood multiple forage harvests without having a large impact on seed yield most years and economics indicate this may be a feasible management practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization. Methods This was a retrospective cohort study, covering a 16-year period at the national tertiary fetal medicine center for management of alloimmunization. Data concerning RhD alloimmunized pregnant women were extracted from an institutional database and maternal anti-D antibody levels were cross-checked with the national reference laboratory. Fetal hemoglobin (Hb) levels were determined only at the first intrauterine transfusion ( IUT) and were compared with the pretransfusion maternal anti-D antibody level ( IU/ mL). Sensitivity, specificity and positive and negative predictive values of maternal antibody thresholds for detecting moderate to severe (Hb ≤ 0. 64MoM) fetal anemia were calculated. Results Between 1996 and 2011, 66 women underwent a first IUT for RhD alloimmunization at our institution. The highest serum anti-D antibody level was extracted for 208 RhD alloimmunized women who did not require IUT during the last 10 years of the study period. The traditional maternal antibody threshold of > 15 IU/ mL failed to detect 20% of cases of moderate to severe fetal anemia. The ≥ 4 IU/ mL threshold had 100% sensitivity but a 45% false-positive rate. The optimal anti-D antibody threshold for specialist referral in our population was ≥ 6 IU/ mL; at this level, no case of moderate to severe anemia was missed and specificity was 61%. Use of this threshold would have eliminated 10% of referrals to our fetal medicine unit without compromising fetal outcomes. Conclusions Setting the critical maternal RhD antibody level at >15 IU/ mL does not provide sufficient sensitivity. The lower threshold of ≥ 4 IU/ mL, though sensitive, is associated with a 45% false-positive rate. In our population, a threshold of ≥ 6 IU/ mL minimizes false-positive referrals while maintaining 100% sensitivity for moderate to severe fetal anemia. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY Objectives To analyse the incidence of additional alloantibody formation following intrauterine red cell transfusion and to evaluate the feasibility of providing extended phenotype-matched red cells in future intrauterine transfusion (IUT). Background IUT is performed in severe, life-threatening fetal anaemia, usually in alloimmunised pregnancies. Its complications include the formation of additional alloantibodies to other red cell antigens. Materials and methods This was an 11-year retrospective, observational study of additional alloantibody formation in patients receiving IUT in the National Maternity Hospital, Dublin. The study included evaluation of the donor population in the Republic of Ireland (RoI) with regards to the feasibility of providing extended phenotype-matched units in future IUT. Results Following IUT, 22% of mothers formed additional red cell alloantibodies. In 67% of cases, the transfused donor red cells expressed the cognate antigen. Suitable donors are available for most combinations of Fy, Jk and Ss antigens. Conclusions In our population, it is feasible to provide more extensively phenotype-matched red cells for future IUT. These can be supplied from the current donor pool with no significant extra phenotyping required. We consider their provision to be a reasonable proactive step in a known at-risk group. [ABSTRACT FROM AUTHOR]

Reasons for performing study Artificial lighting is commonly used to advance the breeding season in horses. Light masks have been developed that direct light at a single eye to inhibit the production of melatonin, the decoder of photoperiod for seasonally breeding animals. Objectives To investigate whether low-intensity blue light from light masks was effective at advancing the breeding season in mares. Study design Controlled experiment. Methods Data on reproductive activity was collected from 3 groups of mares maintained on Kentucky horse farms under various lighting conditions between 20 November 2011 and 10 February 2012: 59 nonpregnant, healthy Thoroughbred mares were used. On 1 December 2011, Group 1 (n = 16) was housed indoors under barn lighting (250 Lux) until 23.00 h daily. Group 2 (n = 25) wore light masks programmed to turn on from 16.30 h until 23.00 h daily and was maintained outdoors. Group 3 (n = 19) was maintained outdoors under the natural photoperiod as control. At 2-week intervals, rectal ultrasound examinations were performed and blood was collected for progesterone analysis. Oestrous cyclicity was defined as the presence of follicles >20 mm diameter detected in conjunction with serum progesterone >1 ng/ml and confirmation of ovulation by transrectal ultrasound examination. Results On 10 February, the number of mares exhibiting oestrous cyclicity was 14/16 (87.5%) in Group 1; 20/25 (80%) in Group 2; and 4/19 (21%), in Group 3. Pairwise comparison of groups revealed no difference in the number of cycling mares between Groups 1 and 2 (χ2 test, P = 0.3348) whereas differences were observed between Groups 1 and 3 (χ2 test, P<0.0001) and Groups 2 and 3 (χ2 test, P<0.0003). Conclusions Low-intensity blue light to a single eye from a light mask is an effective alternative to maintenance of mares indoors under lights for advancing the breeding season. Mobile light therapy for horses could have economic benefits for the breeder by reducing the costs of maintaining mares indoors, and welfare benefits for horses by permitting outdoor maintenance. [ABSTRACT FROM AUTHOR]

SUMMARY Objective To analyse anti-D quantification levels and frequency of intrauterine transfusion (IUT), per maternal ABO blood group. Background Maternally derived red cell allo-antibodies can target fetal red cell antigens in utero leading to haemolytic disease and fetal anaemia. When a clinically significant allo-antibody is formed the priority is ascertaining the risk to the fetus and maternal ABO blood groups are not considered relevant. Materials and methods This was a 10-year retrospective, observational study carried out on women referred for anti-D quantification ( n = 1106), and women whose fetuses required an IUT to treat fetal anaemia ( n = 62) due to anti-D, in the Republic of Ireland. Results Relative to the overall incidence of RhD allo-immunisation by blood group, women of blood group A were more likely to require IUT compared with those who were blood group O ( P = 0·002). Conclusion It is known that ABO feto-maternal compatibility can influence the incidence and level of red cell allo-antibodies in pregnancy; however, it does not account for the significantly high rate of severe haemolytic disease requiring IUT seen in blood group A women. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the evaluation of a novel external tag-mount for acoustic tracking of small fish. Topics include the use of PT-1 acoustic transmitter in the modification of external tagging apparatus, impact of tag attachment on feeding and mortality of Argyrosomus japonicus and Acanthopagrus australis and impact of novel external tagging on trade-off between recovery time and commencement of tracking.

Intra-operative oesophageal Doppler monitor-guided fluid management has been associated with improved postoperative length of hospital stay and morbidity in gastrointestinal and orthopaedic surgery. We designed a randomised controlled trial to test the hypothesis that this approach to intra-operative fluid management in major elective open gynaecological surgery would shorten the length of postoperative stay, defined as time to readiness for hospital discharge. Postoperative morbidity was evaluated as a secondary outcome. The oesophageal Doppler monitor group underwent intra-operative fluid management using an oesophageal Doppler-guided stroke volume optimisation algorithm. Control group (conventional fluid therapy) intra-operative fluid management was based on conventional haemodynamic indices. In a single centre, 102 patients were randomly assigned: 51 to the oesophageal Doppler monitor group (51 analysed) and 51 to the control group (50 analysed). Evaluators who were blinded to patient assignment collected postoperative outcome data. There was no difference in the length of postoperative hospital stay between the groups: median (IQR [range]) number of days until ready for discharge was 6 (5-8 [4-25]) days in the oesophageal Doppler monitor group compared with 7 (5-9 [4-42]) days in the control group, p = 0.5. There was no difference between the groups in postoperative morbidity survey scores on postoperative days 1, 3 or 5. Seven patients in the oesophageal Doppler monitor group and 11 in the control group experienced postoperative complications (p = 0.41). These findings question whether intra-operative oesophageal Doppler-guided fluid therapy is of benefit in patients undergoing open gynaecological surgery. [ABSTRACT FROM AUTHOR]

ABSTRACT The migratory response and behaviour of catadromous Australian bass with regard to hourly mean river flows and water temperatures was assessed over 15 months. Fish movement was assessed using a 75-km passive acoustic telemetry array in the regulated Shoalhaven River below Tallowa Dam, NSW, Australia. The majority (62%) of downstream pre-spawning migrations from freshwater to estuarine habitats were stimulated by a series of flow pulses from April to September, but a proportion of fish (38%) commenced downstream migrations under regulated baseflow conditions after a sustained decrease in water temperature to below 15°C in late autumn. Equal numbers of fish undertook post-spawning upstream return migrations during flow pulses and during regulated baseflow conditions, with regulated baseflow migrants exhibiting a preference for dusk-dawn passage through freshwater pool-riffle sequences. The median magnitude of flow pulses at the time of commencement of downstream and upstream freshwater migrations by Australian bass was not large, equivalent to natural (in the absence of river regulation) flows equalled or exceeded for 56% and 48% of time, respectively. There was no evidence for increased numbers of migrants with increasing flow pulse magnitude, with individual fish ignoring some flow pulses but responding to subsequent events. In regulated rivers, the release of more frequent flow pulses with peak magnitudes approximating the natural 50th flow duration percentile may be more effective in stimulating greater numbers of Australian bass to undertake pre-spawning and post-spawning migrations between freshwater and estuarine habitats than the release of a single, larger event. The propensity of Australian bass to also undertake spawning migrations under regulated baseflow conditions emphasizes the need for provision of baseflow regimes in regulated rivers that can facilitate migrations by large bodied fishes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Selective fetoscopic laser photocoagulation (SFLP) is now the treatment of choice for twin-twin transfusion syndrome (TTTS). The incidence of recurrent TTTS following SFLP has been inconsistently reported across different studies. We performed a systematic review of TTTS recurrence following SFLP. Methods PubMed and MEDLINE online databases were searched for articles published between 2000 and August 2011, using combinations of the terms 'twin-twin transfusion', 'TTTS', 'laser', 'recur' and 'outcome'. Citations identified in the primary search were screened for eligibility. Studies reporting outcomes from selective SFLP for TTTS in twin pregnancies, which addressed specifically the issue of TTTS recurrence, were included. The primary outcome was rate of TTTS recurrence. Secondary outcomes were therapeutic preference and fetal outcomes in cases of recurrent TTTS. Results The primary search identified 22 eligible studies that are included in this review (n = 2447 twin pregnancies). Two studies included a minority of non-selective procedures. The published incidence of recurrent TTTS ranged from 0 to 16%. Clinical management was reported in 65.7% (71/108) cases, with repeat SFLP the most commonly performed secondary intervention. Only three studies provided comprehensive outcome data for cases of recurrent TTTS. The overall rate of neurologically-intact survival was 44% (23/52). The data were inadequate to determine the effects of secondary therapeutic approach, placental location or gestational age on perinatal outcome in cases of recurrent TTTS. Conclusions The published rate of TTTS recurrence following SFLP in monochorionic twin pregnancies ranges from 0 to 16%. Although limited follow-up data suggest that recurrence is associated with significant perinatal mortality and morbidity, further study is needed. Currently, there are insufficient data available to guide recommendations for clinical management of TTTS recurrence. Future studies on SFLP for TTTS must include details on recurrence rates and provide outcome data specific to the recurrent subset. [ABSTRACT FROM AUTHOR]

. Acute haemorrhage treatment in patients with congenital haemophilia with inhibitors (CHwI) has transitioned to home. Patient/caregiver perceptions of bleeding symptoms and reasons for starting/stopping treatment were investigated. Frequently bleeding CHwI patients (≥4 episodes in 3 months) prescribed recombinant factor VIIa (rFVIIa) as first-line therapy, or their caregivers, completed daily diaries for 3-6 months capturing bleeding symptoms and treatment decisions. Thirty-eight patients reported 131 joint, 19 muscle and 44 other bleeding events. Symptoms (all/joint/muscle haemorrhages) included pain (78.9%/90.1%/89.5%), joint swelling (44.8%/65.6%/5.3%), decreased mobility (41.2%/48.9%/68.4%), local warmth (21.1%/26.0%/15.8%), other swelling (16.0%/6.9%/47.4%), irritability (14.9%/16.8%/10.5%), visible bleeding (12.4%/7.6%/5.3%) and redness (10.3%/6.1%/10.5%). Most patients/caregivers recognized when bleeds started (58.4%/58.0%), but were less clear when bleeds stopped (43.5%/33.3%). Medication was commonly started by patients/caregivers when bleeds were identified (73.7%/47.4%) or when concerned bleeds might start (32.9%/27.6%). Common reasons for delays in starting medication by patients included 'I thought it might not be a bleed' (48.9%), 'I wanted to see if the bleed progressed' (46.8%) and 'I thought it was just joint pain' (44.7%). Common reasons for caregivers were: 'I wanted to see if it progressed' (37.9%), 'I didn't have medication' (20.7%) and 'I thought it might not be a bleed' (17.2%). Reasons for stopping medication for patients/caregivers were pain cessation/stabilization (93.9%/54.7%), arrest of swelling progression (60.6%/46.9%) and improved mobility (50.0%/35.9%). Patients/caregivers have difficulty in determining bleed onset and particularly resolution, both quite necessary for treatment decisions and clinical trials. Caregivers' inability to assess resolution in children may lead to longer treatment duration seen in the Dosing Observational Study in Haemophilia (DOSE). [ABSTRACT FROM AUTHOR]

ABSTRACT Thermoduric gram-positive bacteria are indigenous in milk, cheese, whey and other dairy products. They are capable of surviving heat processes and can result in quality defects and a shortened product shelf life. In Ireland, premium products such as whey protein concentrate (WPC) are often adversely affected by these microorganisms, particularly during the winter months. A high bacterial count in the WPC can result in the product being sold at a lower grade, with an overall loss of revenue for the manufacturer. This study recovered thermoduric bacterial isolates ( n = 140) from an Irish WPC process during the months of November-February. Using molecular 16S rRNA gene identification, Bacillus licheniformis, Microbacterium lacticum, Staphylococcus warneri, Enterococcus durans and Bacillus subtilis were recorded as the predominant microorganisms in this process line. This is the first known study to report the detection of Microbacterium phyllosphaerae, Neisseria subflava, Rothia aeria and Streptococcus mitis in dairy produce or indeed in any food product. The identification of bacteria at various stages of the WPC production process will support future measures in reducing/removing microorganisms from the process line in question and assist the dairy manufacturer in tackling this costly problem. PRACTICAL APPLICATIONS Through the use of 16S rRNA gene typing, we have accurately identified the bacteria that were present at various stages of the WPC production process in this facility. Molecular methods are not routinely used in this setting. Nonetheless, they can confer important advantages in terms of their accuracy and speed. These findings support a translated improvement in bacterial identification, allowing us to not only trace but also to strategically reduce/eliminate certain microflora from the production process. The latter step can have the effect of reducing the overall bacterial load of the matrix while simultaneously improving its shelf-life characteristics. These findings will assist in the development of measures to improve the quality and safety of WPC production at this plant. This study highlights the potential benefits of using molecular techniques in a food processing environment. [ABSTRACT FROM AUTHOR]

. Patients with congenital haemophilia with inhibitors experience acute bleeds managed with bypassing agents, such as recombinant FVIIa (rFVIIa). Home-based treatment and dosing patterns in the US remain poorly described. This study aimed to assess the prescribed and actual rFVIIa dosing in frequently bleeding inhibitor patients (≥4 bleeds in 3 months) prescribed first-line therapy with rFVIIa. Patients or caregivers recorded daily diaries, including the details of all bypassing agent infusions for 3-6 months. Median (range) initial rFVIIa dose prescribed for joint, muscle and other bleeds was 167.5 (61.0-289.0) mcg kg−1. Additional rFVIIa doses prescribed were 90 (61-270) mcg kg−1 at an interval of 2.5-3 (1-24) h. The actual initial rFVIIa dose reported by patients/caregivers for 158 bleeds was 212 (59-400) mcg kg−1, with total dose per episode of 695 (74-21257) mcg kg−1. Patient/caregiver-reported average dose per bleed was 146 (40-400) mcg kg−1 across 5 (1-106) infusions. The initial rFVIIa dose was higher for haemarthrosis (223 [59-400] mcg kg−1) than muscle bleeds (148 [74-300] mcg kg−1; P = 0.07). Initial and mean dose per day changed as treatment progressed. The DOSE study indicates that frequently bleeding inhibitor patients are prescribed and use higher rFVIIa dosing for all bleed types than recommended in the package insert (90 mcg kg−1). The rFVIIa dosing was highly variable within and across bleed types, with higher initial doses used for joint bleeds than muscle and other bleed types, particularly in the first days of treatment. This suggests that patients/caregivers have adopted home treatment strategies based on physician discretion and individual responses and experience. [ABSTRACT FROM AUTHOR]

Background Loneliness has been associated with poor physical health and a link has been suggested between the presence of loneliness, cardiovascular health and inflammatory markers. Objective To investigate the association between vascular disease biomarkers and loneliness in a community-dwelling non-demented elderly population. Design cross-sectional community based assessment. Participants 466 subjects with mean age 75.45 (SD, 6.06) years. 208 (44.6%) were male. Results Higher levels of HbA1c, but not other vascular biomarkers were independently associated with being lonely. Conclusion Loneliness was associated with raised levels of HbA1c in a community dwelling elderly population. The mechanism for this association has yet to be elucidated but may reflect an abnormal stress response in people who are lonely. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim Previous studies have implicated stoma formation as an independent factor prolonging length of stay (LOS) after colorectal surgery. We examined whether loop ileostomy (LI) formation during an open anterior resection affected LOS within a newly developed enhanced recovery programme (ERP). This involved reorganization of services, including stoma care, to optimize pre- and perioperative patient education, training and expectation, while applying the standard scientific principles of enhanced recovery. Method Data were collected prospectively on 72 consecutive open anterior resections (33 with LI) to see whether LI affected LOS. Stomas were fashioned at the surgeon's discretion and patients were discharged according to agreed criteria. Results Thirty-three of the 72 patients had a covering LI performed. The overall age range was 32-85 years (median 68), with 40 patients being men. LOS for all 72 patients ranged from 3 to 34 days. The median and mean LOS were the same for both groups (median 6 days, mean 8 days). The complication rate was 44% (32/72) with a leak rate of 7% (5/72) and a mortality of 1.4% (1/72). Between the two groups (no ileostomy vs ileostomy), there was no statistically significant difference in complications (41% vs 48%), leakage (8% vs 6%) and readmission rates (12% vs 5%). Conclusion A covering loop ileostomy need not prolong hospital stay after open anterior resection. [ABSTRACT FROM AUTHOR]

Background It has been reported that late onset depression is more frequently associated with acquired organic pathology and that patients are less likely to report a family history of depression. Differences in phenomenology according to age of onset have been described although these have not been consistently replicated. The majority of these studies have been in hospital populations. The aim of this study is to address this question in a sample of community dwelling older adults. Methods 89 subjects with GMS-AGECAT depression were identified from a sample of 1231 community dwelling adults aged 65 years and over. Subjects were analysed across a range of aetiological and phenomenological variables according to age of onset of first depressive episode. Results Subjects with late onset depression (≥ 60) were significantly less likely to report a family history of depression, were less likely to report previous hospitalisation for depression and had greater cognitive impairment. Late onset subjects were also less likely to report feelings of guilt or thoughts that life was not worth living in the previous month. Conclusion While we found that patients with late onset depression differed from early onset patients according to certain aetiological risk factors, we did not find a distinctive profile of depressive symptomatology which might be considered clinically useful at an individual level. These findings are consistent with studies based in hospital populations. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The main focus of lower limb physical performance assessment in people with haemophilia (PWH) has usually been on function, muscle strength and joint flexibility. The impact of haemophilic arthropathy on balance and falls risk is relatively under-explored. The aim of this study was to evaluate balance and related performance in PWH compared with age and gender matched healthy controls. It involved a comprehensive suite of clinical and laboratory measures of static and dynamic balance, mobility, strength, physical activity and falls efficacy completed in 20 PWH (mean age 39.4, 100% male) and 20 controls. Fifty percent of PWH reported falls in the past 12 months. Moderate impairment of balance and related measures were identified in PWH compared with the controls, with an average 35% difference between groups. Significant differences were evident between groups on both clinical and laboratory measures, including measures of dynamic bilateral stance balance [limits of stability measures on the laboratory test, functional reach; ( P < 0.001); dynamic single leg balance (Step Test, P < 0.001)], gait and mobility (gait speed, step width and turning measures on the laboratory test, timed up and go test; P < 0.001); muscle strength (timed sit to stand, P = 0.002; quadriceps strength, P < 0.001); and activity level and falls efficacy, ( P < 0.004). The dynamic clinical and laboratory measures testing similar domains of balance, gait and mobility had moderate correlations (0.310 < r < 0.531, P < 0.01). Moderate impairments in balance, mobility and related measures were identified in PWH, compared with the control group. Clinicians should include assessments of balance and related measures when reviewing adults with haemophilia. [ABSTRACT FROM AUTHOR]

Background: Observational studies of the impact of care delivered in stroke units on mortality after acute stroke have been difficult to interpret because of bias. Methods: This study used Bayesian methodology to (i) sequentially update current knowledge based on a systematic review of observational studies, (ii) adjust for the likely effect of observational bias in a conservative, scenario-based approach and (iii) evaluate the likely impact of further studies. The data were interpreted both unmodified and adjusted for bias by explicitly correcting for point estimate and precision bias. Results: As of 2007, the total evidence base was almost 47 000 patients. The unadjusted data yielded a current 95% posterior credible interval (Cr.I.) for the odds ratio of death within 1 year after stroke unit versus alternative models of stroke care of (0.77, 0.85). Given the adjusted data, the current 95% Cr. I. is (0.79, 0.93). Conclusions: The current estimates are robust, with demonstrable stability despite the addition of recent large studies. Further studies are very unlikely to alter current knowledge but may have a role in ensuring regional stability of outcome. [ABSTRACT FROM AUTHOR]

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7–45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance ( P = 0.036) and Timed Sit to Stand ( P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme. [ABSTRACT FROM AUTHOR]

The emergence of a population of relatively healthy adults with severe haemophilia A presents a unique challenge for haemophilia care in the 21st century. Understanding how best to continue, restart, initiate or modify prophylaxis in younger and older adult patients is essential to optimizing their care. To elucidate practice and outcome data, a survey was sent to 23 US hemophilia treatment centers (HTCs); 10 centers responded, providing data concerning up to 145 adults (mean age of 34 years). Forty-eight patients (33%) were on regular prophylaxis when first seen at the HTC; the prophylactic regimen was modified for 22/48 (46%), often because of breakthrough bleeding. Five of 21 patients (24%) for whom data were available discontinued prophylaxis. Three of those five patients (60%) experienced increased bleeding episodes and the other two (40%) subsequently resumed regular prophylactic infusions because of the increased bleeding. Of the 77 patients not initially receiving prophylaxis for whom data were available, prophylaxis was started or resumed in all. The prophylactic regimen was modified in 57/77 patients (74%) at some point during treatment, often because of breakthrough bleeding. Of the 55 patients whose prophylactic regimens were modified for whom data were available, 22 (40%) discontinued prophylaxis. Thirteen of 20 patients (65%) for whom data were available experienced an increase in bleeding episodes and 7/18 patients (39%) who had discontinued prophylaxis and for whom data were available subsequently resumed regular prophylactic infusions because of bleeding. These findings suggest that prophylaxis prevents bleeding in adults with severe haemophilia A and that discontinuation of the prophylactic regimen is associated with increased bleeding events. [ABSTRACT FROM AUTHOR]

Objectives: To assess attributes of sevoflurane for routine clinical anaesthesia in dogs by comparison with the established volatile anaesthetic isoflurane. Methods: One hundred and eight dogs requiring anaesthesia for elective surgery or diagnostic procedures were studied. The majority was premedicated with 0·03 mg/kg of acepromazine and 0·01 mg/kg of buprenorphine or 0·3 mg/kg of methadone before induction of anaesthesia with 2 to 4 mg/kg of propofol and 0·5 mg/kg of diazepam. They were randomly assigned to receive either sevoflurane (group S, n=50) or isoflurane (group I, n=58) in oxygen and nitrous oxide for maintenance of anaesthesia. Heart rate, respiratory rate, indirect arterial blood pressure, haemoglobin saturation, vaporiser settings, end-tidal carbon dioxide and anaesthetic concentration and oesophageal temperature were measured. Recovery was timed. Data were analysed using analysis of variance and non-parametric tests. Results: Heart rate (85 to 140/minute), respiratory rate (six to 27/minute) and systolic arterial blood pressure (80 to 150 mmHg) were similar in the two groups. End-tidal carbon dioxide between 30 and 60 minutes (group S 6·4 to 6·6 and group I 5·8 to 5·9 per cent) and vaporiser settings throughout (group S 2·1 to 2·9 and group I 1·5 to 1·5 per cent) were higher in group S. There was no difference in time to head lift (18±16 minutes), sternal recumbency (28±22 minutes) or standing (48±32 minutes). No adverse events occurred. Clinical Significance: Sevoflurane appeared to be a suitable volatile anaesthetic for maintenance of routine clinical anaesthesia in dogs. [ABSTRACT FROM AUTHOR]

Background The diagnosis of dementia poses difficulties for general practitioners (GPs) particularly when access to specialist diagnostic services is delayed. Ireland is soon to witness an increase in numbers of people presenting with dementia, yet little is known about the service needs of GPs when attempting to diagnose dementia. Objectives To detail the service needs of GPs, especially their training needs, access to diagnostic resources such as CT and MRI brain scans and access to specialist services such as Old Age Psychiatry (OAP), Geriatric Medicine (GM) and Neuropsychology (NP). Methods The paper is based on survey data collected from a sample of GPs (n = 300) registered with the Irish College of General Practitioners (ICGP) and on qualitative data collected from a Focus Group (n = 7). Results GPs were more likely to blame themselves than either the health care system, their patients or family members for the late presentation of dementia in primary care. Stigma was a major obstacle preventing GPs from being more proactive in this area. Rural GPs felt geographically disadvantaged accessing diagnostic services and both rural and urban GPs experienced considerable time delays accessing specialist diagnostic services. Conclusions Findings provide compelling evidence that training and access to diagnostic services are only two of several different structural and ideological obstacles that GPs encounter when attempting to diagnose dementia. Future educational supports for GPs need to be developed which concentrate on these areas.Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

(i) To determine whether neurology is the medical specialty with which Irish students and doctors have most difficulty, (ii) appraise attitudes towards how neurology is taught, and (iii) suggest ways teaching might be improved. A questionnaire on medical teaching was given to 457 medical students and junior doctors in Ireland. Perceived difficulties with neurology compared with seven other medical specialties were analysed. Other aspects of teaching were assessed including why neurology is perceived as difficult and ways teaching could be improved. Neurology was perceived as the most difficult of the eight medical specialties assessed. Participants felt they learned most at bedside tutorials with surprisingly few learning online. Neurology was perceived as difficult because of insufficient exposure to the subject, lack of teaching, and perceived complexity. Neurology teaching could be improved by increasing the number of bedside tutorials and by greater exposure to neurological patients for the students in clinical training. Medical students and doctors find neurology difficult. The teaching of neurology is reported as moderate to poor. The reasons for this are wide ranging but an emphasis on increased numbers of tutorials and greater integration of pre-clinical neurology to clinical years would improve teaching. [ABSTRACT FROM AUTHOR]

Schistosoma mansoni infection of mice increases the frequency of cells that are CD4+CD25+ in the acute (4 and 8 weeks) and chronic (16 week) stages of infection. Depletion of > 85% of CD25+ cells in the acute or chronic stages of schistosome infection caused no overt changes in morbidity or immunological responses. The absence of effect in mice with CD25+ cells depleted may be due to the preferential expression of IL-4 and IL-10, two cytokines that are protective in schistosome infection, on CD25− CD4+ cells. We also assessed infection-induced changes of other regulatory markers, GITR, CD103 and CTLA-4 on CD4+ cells. We identified a marked expansion of CTLA-4+ population on CD25− CD4+ cells in acute and chronic infection. Blocking of CTLA-4 during acute, but not chronic infection, caused significant weight loss and altered the type 2 cytokine response of mice, with increased IL-4 and IL-5 production associated with significantly more Th2 cells and eosinophils in the liver granuloma. This study illustrates the complexity of regulation of T cells in schistosome infection and highlights a specific role for CTLA-4+, but not CD25+ cells, in the regulation of Th2 responses in helminth infection. [ABSTRACT FROM AUTHOR]

Objective To determine the frequency of unrecognised dementia in a group of community dwelling elderly, and to identify factors associated with dementia recognition by informants. Sample selection People over 65 years with an AGECAT case or subcase organic diagnosis or an MMSE ≤ 23 were identified from a database of community dwelling elderly. A psychiatrist to confirm the diagnosis of dementia according to ICD-10 criteria interviewed these individuals. Study participants Sixty-two community dwelling elderly meeting ICD-10 criteria for dementia whom had reliable informants. Methods Prior to the start of the interview the informant was questioned about whether they felt the patient had memory difficulties and if so whether they had a medical evaluation for their memory problems. A psychiatrist then interviewed the patient and informant to establish whether that patient met ICD-10 criteria for dementia. Basic sociodemographic details were collected and the following assessments were carried out: the Blessed Dementia Rating Scale, the Clinical Dementia Rating Scale, the Behave-AD and the Baumgarten Behavioural Disturbance Scale. Analysis Univariate and step-wise forward logistic regression analysis were used to examine the factors associated with recognition of memory difficulties. Results Twenty-nine percent of family informants of people with dementia failed to recognise a problem with their relatives'memory. Where memory difficulties were recognised only 39% of this group received a medical evaluation. Using univariate analysis recognition of memory difficulties by family informants was associated higher levels of behaviour disturbance ( p = < 0.0011), greater functional impairment ( p = 0.0039), with increasing cognitive impairment ( p = 0.013). Using a logistic regression model, to test the independence of these variables, increasing behavioural disturbance (p = 0.0001) was associated with recognition of dementia by family informants. Conclusions Recognition of memory problems by family members is associated with increasing behavioural disturbance. Even with recognition of dementia, families often fail to seek medical attention. Education of the lay public on the early signs and symptoms of dementia must be a key first step in improving recognition of dementia in the community dwelling elderly. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multi-day rainfall events appear to be an important cause of recent flooding in the UK. Hydrological data from an extensive, nested hydrometric network in the unregulated, predominantly rural Upper Eden catchment in northern England are presented for one such flood event. These highlight antecedent catchment conditions and the propagation of the multi-day flood event during February 2004. An assessment of flood response is provided over varying scales and land use between the upland Gais Gill catchment (1.1 km2) and the larger Upper Eden catchment (616 km2). Large spatial variations in rainfall totals are identified from a dense raingauge network during the flood event and are principally related to catchment elevation. High cumulative rainfall totals for the 6-day event, particularly at upland sites appear to be the exceptional feature of the flood event with return periods in the order of 100 years at some upland gauges. Resultant patterns of flood attenuation and translation are quantified in different areas of the catchment, highlighting the flashy response of the headwater catchments and the attenuated downstream response in the lowland environment. The study forms part of the national Catchment Hydrology And Sustainable Management (CHASM) programme. [ABSTRACT FROM AUTHOR]