Perinatal outcome of fetuses predicted to be large-for-gestational age on universal third-trimester ultrasound in non-diabetic pregnancy.

OBJECTIVE: To describe the perinatal outcome of fetuses predicted to be large-for-gestational age (LGA) on universal third-trimester ultrasound in non-diabetic pregnancies of women attempting vaginal delivery. METHODS: This was a prospective population-based cohort study of patients from a single tertiary maternity unit in the UK offering universal third-trimester ultrasound and practicing expectant management of suspected LGA until 41-42 weeks. All women with a singleton pregnancy and an estimated due date between January 2014 and September 2019 were included. Women delivering before 37 weeks, those having a planned Cesarean delivery, those with pre-existing or gestational diabetes, those with fetal abnormalities and those who did not undergo a third-trimester scan were excluded from the assessment of perinatal outcome of cases with LGA predicted on ultrasound after implementation of the universal scan period. Association of LGA on universal third-trimester ultrasound screening and perinatal adverse outcome was assessed, with the exposures of interest being estimated fetal weight (EFW) at the 90th -95th , > 95th and > 99th percentile. The reference group was composed of fetuses with EFW at the 30th -70th percentile. Analysis was performed using multivariate logistic regression. The evaluated adverse perinatal outcomes included a composite outcome of admission to neonatal intensive care unit, Apgar score < 7 at 5 min and arterial cord pH < 7.1 (CAO1) and a composite outcome of stillbirth, neonatal death and hypoxic ischemic encephalopathy (CAO2). Secondary maternal outcomes were induction of labor, mode of delivery, postpartum hemorrhage, shoulder dystocia and obstetric anal sphincter injury. RESULTS: Cases with EFW > 95th percentile on universal third-trimester scan were at increased risk of CAO1 (adjusted odds ratio (aOR), 2.18 (95% CI, 1.69-2.80)) and CAO2 (aOR, 2.58 (95% CI, 1.05-6.34)). Cases with EFW at the 90th -95th percentile had a less pronounced increase in the risk of CAO1 (aOR, 1.35 (95% CI, 1.02-1.78)) and were not at increased risk of CAO2. All pregnancies with a fetus predicted to be LGA were at increased risk of all of the evaluated secondary maternal outcomes except for obstetric anal sphincter injury. The risk of adverse maternal outcome was typically higher with increasing EFW. Post-hoc exploration of data suggested that shoulder dystocia had a limited contribution to composite adverse perinatal outcomes in LGA cases (population attributable fraction of 10.8% for CAO1 and 29.1% for CAO2). CONCLUSIONS: Cases with EFW > 95th percentile are at increased risk of severe adverse perinatal outcome, such as death and hypoxic ischemic encephalopathy. These findings should aid antenatal counseling regarding the associated risk and delivery options. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Health-related quality of life in patients with Achilles tendinopathy: Comparison to the general population of the United Kingdom.

BACKGROUND: There is little evidence available regarding the impact of Achilles Tendinopathy (AT) on health-related quality of life (HRQOL). The primary aim of this study was to quantify the clinical and health-related quality-of-life patient-reported outcome measures for a population presenting with either mid-substance or insertional Achilles tendinopathy. METHODS: A prospective comparative observational study of consecutive patients with AT presenting for extracorporeal shockwave therapy (ESWT) at a large teaching hospital. The primary outcome was assessment of a validated health-related quality of life PROMs (Euroqol EQ-5D-5L) and comparison to 2 general UK population datasets. The secondary outcomes were Visual Analogue Pain Scale (VAS-Pain) and two validated foot-specific patient reported outcome measures (Foot Function Index (FFI) and Victorian Institute of Sports Assessment-Achilles (VISA-A)). RESULTS: Between March 2014 and June 2021, 320 consecutive patients (125 male; 195 female) were diagnosed with AT and referred for a first course of ESWT. EQ-5D-5L PROMs were prospectively collected for 303 of these patients (94.7%). The mean age (± standard deviation(SD)) was 52.1 ± 11.4 years. The mean EQ-5D-5L Index score (mean±SD) for the AT cohort was 0.783 ± 0.131. Patients less than 55 years with AT had a statistically significantly worse quality of life compared with members of the same age group in the general population. The mean VAS-Pain, FFI, VISA-A clinical outcome scores were 6.0 ± 2.3, 49.5 ± 21.2 and 34.1 ± 14.4 respectively. There was a statistically significant moderate correlation between HRQOL and clinical PROMs (VAS-Pain and FFI vs EQ-5D) however there was no correlation with age. CONCLUSION: This study demonstrates that patients under the age of 55 with AT have a significantly reduced quality of life compared with the general population. LEVEL OF EVIDENCE: III.

HIV-associated neurocognitive impairment in stable people living with HIV on ART in rural Tanzania.

OBJECTIVES: Few studies have assessed cognitive impairment among healthy people living with HIV (PLWH) who are stable on antiretroviral treatment (ART) in sub-Saharan Africa. METHODS: We conducted a cross-sectional study among a random sample of stable adult PLWH from rural Tanzania on ART for more than 1 year and without immunological failure or pre-existing neurological disease. We evaluated the prevalence and risk factors for neurocognitive impairment (NCI), assessed through neuropsychological tests, functional and depression questionnaires and defined as a mean Z-score ≤ -1 in two or more cognitive domains. RESULTS: Among 243 participants [median age = 44.3 years (interquartile range: 36-52] and 71% female] we found a rate of NCI of 19.3% (95% confidence interval: 14.8-24.8%). Memory and psychomotor domains demonstrated the highest impairment. Independent predictors of NCI were age and self-reported alcohol use. Other classical risk factors were not associated with HIV-associated NCI. CONCLUSION: Despite effective ART roll-out, NCI remained a prevalent condition in this healthy rural Tanzanian population of PLWH on ART. Age and alcohol use were key risk factors.

An inexpensive retrospective standard setting method based on item facilities.

BACKGROUND: Standard setting is one of the most challenging aspects of assessment in high-stakes healthcare settings. The Angoff methodology is widely used, but poses a number of challenges, including conceptualisation of the just-passing candidate, and the time-cost of implementing the method. Cohen methodologies are inexpensive and rapid but rely on the performance of an individual candidate. A new method of standard setting, based on the entire cohort and every item, would be valuable. METHODS: We identified Borderline candidates by reviewing their performance across all assessments in an academic year. We plotted the item scores of the Borderline candidates in comparison with Facility for the whole cohort and fitted curves to the resulting distribution. RESULTS: It is observed that for any given Item, an equation of the form y ≈ C. eFx where y is the Facility of Borderline candidates on that Item, x is the observed Item Facility of the whole cohort, and C and F are constants, predicts the probable Facility for Borderline candidates over the test, in other words, the cut score for Borderline candidates. We describe ways of estimating C and F in any given circumstance, and suggest typical values arising from this particular study: that C = 12.3 and F = 0.021. CONCLUSIONS: C and F are relatively stable, and that the equation y = 12.3. e0.021x can rapidly be applied to the item Facility for every item. The average value represents the cut score for the assessment as a whole. This represents a novel retrospective method based on test takers. Compared to the Cohen method which draws on one score and one candidate, this method draws on all items and candidates in a test. We propose that it can be used to standard set a whole test, or a particular item where the predicted Angoff score is very different from the observed Facility.

Discordant rapid HIV tests: lessons from a low-resource community.

OBJECTIVES: HIV rapid antibody tests are widely used in Africa, but dual testing sometimes produces discordant results. It is not clear if discordant rapid HIV tests should always heighten suspicion by frontline health workers that early HIV infection is present. Some studies have reported that discordant rapid tests have value for identifying early HIV infection in high HIV prevalence populations. It is not known if rapid test performance influenced this conclusion, or if this observation will hold true for low HIV prevalence populations. We therefore explored the occurrence of discordant rapid HIV tests in a low-resource community. METHODS: A cross-sectional sample of HIV status-unaware adults with recent exposure to unsafe sex was assessed using a validated risk-based tool (University of North Carolina (UNC)-Malawi Risk Screening Score) for acute HIV infection. Participants received rapid testing with Determine™ HIV 1/2 and Uni-Gold™ HIV assays, plus plasma HIV-1 antigen testing with the COBAS® Ampliprep/COBAS® Taqman® HIV-1 assay, followed by western blot in those with detected HIV-1 antigen. RESULTS: Of 408 participants, 1.0% were confirmed to have established HIV infection. The discordance between rapid tests at initial screening was 2.45 and 2.94% when the two assays were used sequentially and simultaneously, respectively. Discordant rapid tests were strongly associated with risk scores > 2 [odds ratio (OR) 10.88; 95% confidence interval (CI) 2.35-50.43], and with detected HIV-1 RNA (OR 26.06; 95% CI 3.91-173.60). CONCLUSIONS: When the sample occurrence of discordance between the first and second tests is below 5%, discordant rapid tests in an adult with sexual risk behaviour should trigger strong suspicion of early HIV infection in low HIV prevalence populations.

Dulaglutide decreases plasma aminotransferases in people with Type 2 diabetes in a pattern consistent with liver fat reduction: a post hoc analysis of the AWARD programme.

AIMS: To evaluate the effects of dulaglutide vs placebo on liver and glycaemic/metabolic measurements in a population with Type 2 diabetes and in a subgroup with non-alcoholic fatty liver/non-alcoholic steatohepatitis. METHODS: A total of 1499 participants from AWARD-1, AWARD-5, AWARD-8 and AWARD-9 clinical trials were included in this analysis (dulaglutide 1.5 mg, n=971 and placebo, n=528). Thresholds of alanine aminotransferase levels ≥30 IU/l in men and ≥19 IU/l in women were used to determine the subgroup who had non-alcoholic fatty liver/non-alcoholic steatohepatitis. Objectives included changes from baseline to 6 months in: (1) alanine aminotransferase, aspartate transaminase and gamma-glutamyl transpeptidase levels in the overall population and (2) alanine aminotransferase, aspartate transaminase, gamma-glutamyl transpeptidase and glycaemic/metabolic measurements (e.g. HbA1c , fasting serum glucose, body weight, lipids and homeostatic model assessment) in the non-alcoholic fatty liver/non-alcoholic steatohepatitis subgroup. RESULTS: In the overall population at 6 months, dulaglutide significantly reduced alanine aminotransferase, aspartate transaminase and gamma-glutamyl transpeptidase levels vs placebo [least squares mean treatment differences: -1.7 IU/l (95% CI -2.8, -0.6), P=0.003; -1.1 IU/l (95% CI -2.1, -0.1), P=0.037; -6.6 IU/l (95% CI -12.4, -0.8), P=0.025, respectively]. In the subgroup with non-alcoholic fatty liver/non-alcoholic steatohepatitis (alanine aminotransferase levels greater than or equal to the upper limit of normal), mean baseline liver enzyme values were 38.0 IU/l, 27.8 IU/l and 43.9 IU/l for alanine aminotransferase, aspartate transaminase and gamma-glutamyl transpeptidase, respectively. In this population, more pronounced reductions from baseline in alanine aminotransferase were observed with dulaglutide vs placebo (-8.8 IU/l vs -6.7 IU/l). In the subgroup of people with alanine aminotransferase levels less than the upper limit of normal, changes from baseline in alanine aminotransferase did not significantly differ between treatment groups (0.0 IU/l vs 0.7 IU/l). CONCLUSIONS: Once-weekly dulaglutide improved alanine aminotransferase, aspartate transaminase and gamma-glutamyl transpeptidase levels compared with placebo in a pattern consistent with liver fat reductions. Our results add further weight to the notion that glucagon-like peptide-1 receptor agonists may provide benefit in lowering liver fat in addition to their other metabolic actions.

A New Picture of Fire Extent, Variability, and Drought Interaction in Prescribed Fire Landscapes: Insights From Florida Government Records.

Florida, United States, government records provide a new resource for studying fire in landscapes managed with prescribed fire. In Florida, most fire area (92%) is prescribed. Current satellite fire products, which underpin most air pollution emission inventories, detect only 25% of burned area, which alters airborne emissions and environmental impacts. Moreover, these satellite products can misdiagnose spatiotemporal variability of fires. Overall fire area in Florida decreases during drought conditions as prescribed fires are avoided, but satellite data do not reflect this pattern. This pattern is consistent with prescribed fire successfully reducing overall fire risk and damages. Human management of prescribed fires and fuels can, therefore, break the conventional link between drought and wildfire and play an important role in mitigating rising fire risk in a changing climate. These results likely apply in other regions of the world with similar fire regimes.

Comparison of endoscopic laser therapy and self expanding metal stents for palliation in patients with non-resectable oesophageal carcinoma.

BACKGROUND: There are currently limited data on the comparative success of endoscopic laser therapy (NLT) and self expanding metal stents (SEMS) as palliative measures in patients with non-resectable oesophageal cancer. This study aims to assess and compare the outcomes of these methods of endoscopic palliation. METHODS: Patients with non-curative oesophageal/gastro-oesophageal cancers with dysphagia were identified prospectively and consented to swallow assessment and follow-up. Patients underwent SEMS or NLT at the discretion of the treating endoscopist. Initial standardised swallow scores (0-4) were assessed. All subsequent interventions were recorded as well as survival. RESULTS: 31 patients were recruited (30M vs 8F, mean age 70.8). There was no significant difference in age, sex or chemotherapy treatment between groups. 19(61%)patients underwent NLT as primary procedure. 20(64.5%) patients required subsequent intervention(s) (median 1, range 0-8). Primary NLT patients were more likely to require subsequent therapy (p = 0.004) and multiple procedures (p = 0.001). 8(42.1%)patients initially undergoing NLT subsequently required SEMS, while no SEMS patients underwent subsequent NLT. Swallow scores of 1 or 2 were more likely to be maintained with NLT while scores of 3 or 4 were more likely to progress to SEMS (p = 0.039). Time to repeat procedure was greater in the SEMS group (p = 0.001). Median survival was 133 days for NLT vs 60 days for SEMS (p = 0.412). CONCLUSION: In this series, patients selected for NLT had a trend towards longer survival, but were more likely to require repeated procedures. Those with lower early initial dysphagia scores were more likely to be maintained by NLT alone.

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271.

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n = 240), India (n = 480), Malawi (n = 481), Peru (n = 239), South Africa (480), Thailand (n = 240), and Zimbabwe (n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.

A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8).

AIMS: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. METHODS: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. RESULTS: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported. CONCLUSIONS: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.

Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: We describe neuropsychological test performance (NP) in antiretroviral treatment (ART)-naïve HIV-positive individuals with CD4 cell counts above 500 cells/µL. METHODS: In a neurology substudy of the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of AntiRetroviral Treatment (START) study, eight neurocognitive tests were administered. The primary measure of NP was the quantitative NP z-score (QNPZ-8), the average of the z-scores for the eight tests. Associations of baseline factors with QNPZ-8 scores were assessed by multiple regression. Mild neurocognitive impairment (NCI) was defined as z-scores < -1 in at least two of six cognitive domains. RESULTS: A total of 608 participants had a median age of 34 years; 11% were women and 15% were black; the median time since HIV diagnosis was 0.9 years; the median CD4 cell count was 633 cells/µL; 19.9% had mild NCI. Better NP was independently associated with younger age, being white, higher body mass index (0.10 per 10 kg/m(2) higher), and higher haematocrit percentage (0.19 per 10% higher). Worse NP was associated with longer time since HIV diagnosis (-0.17 per 10 years), diabetes (-0.29) and higher Framingham risk score (-0.15 per 10 points higher). QNPZ-8 scores differed significantly between geographical locations, with the lowest scores in Brazil and Argentina/Chile. CONCLUSIONS: This is the largest study of NP in ART-naïve HIV-positive adults with CD4 counts > 500 cells/µL. Demographic factors and diabetes were most strongly associated with NP. Unmeasured educational/sociocultural factors may explain geographical differences. Poorer NP was independently associated with longer time since HIV diagnosis, suggesting that untreated HIV infection might deleteriously affect NP, but the effect was small.

HIV eradication symposium: will the brain be left behind?

On 18 July 2014, the National Institute of Mental Health in collaboration with ViiV Health Care and Boehringer Ingelheim supported a symposium on HIV eradication and what it meant for the brain. The symposium was an affiliated event to the 20th International AIDS Conference. The meeting was held in Melbourne, Australia, and brought together investigators currently working on HIV eradication together with investigators who are working on the neurological complications of HIV. The purpose of the meeting was to bring the two fields of HIV eradication and HIV neurology together to foster dialogue and cross talk to move the eradication field forward in the context of issues relating to the brain as a potential reservoir of HIV. The outcomes of the symposium were that there was substantive but not definitive evidence for the brain as an HIV reservoir that will provide a challenge to HIV eradication. Secondly, the brain as a clinically significant reservoir for HIV is not necessarily present in all patients. Consequently, there is an urgent need for the development of biomarkers to identify and quantify the HIV reservoir in the brain. Lastly, when designing and developing eradication strategies, it is critical that approaches to target the brain reservoir be included.

Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

Validating a refractometer to evaluate immunoglobulin G concentration in Jersey colostrum and the effect of multiple freeze-thaw cycles on evaluating colostrum quality.

The objectives of this study were to (1) validate a method using refractometry to rapidly and accurately determine immunoglobulin (IgG) concentration in Jersey colostrum, (2) determine whether there should be different refractive index (nD) and %Brix cut points for Jersey colostrum, and (3) evaluate the effect of multiple freeze-thaw (FT) cycles on radial immunodiffusion (RID) and a digital refractometer to determine IgG concentration in Jersey colostrum. Samples (n=58; 3L) of colostrum were collected from a dairy in northwestern Iowa. Samples were analyzed within 2h of collection for IgG concentration by RID, %Brix, and nD by refractometer and an estimate of IgG by colostrometer. Samples were frozen, placed on dry ice, and transported to the laboratory at Iowa State University (Ames). Samples arrived frozen and were placed in a -20°C manual-defrost freezer until further analysis. On d 7 (1FT), d 14 (2FT), and 1yr (3FT) all samples were thawed, analyzed for IgG by RID, %Brix, nD by refractometer, and IgG estimate by colostrometer, and frozen until reanalysis at the next time point. Fresh colostrum had a mean (±SD) IgG concentration of 72.91 (±33.53) mg/mL, 21.24% (±4.43) Brix, and nD 1.3669 (±0.0074). Multiple FT cycles did affect IgG as determined by RID and colostrometer reading. The IgG concentrations were greater in fresh and 1FT samples as compared with 2FT and 3FT samples (72.91, 75.38, 67.20, and 67.31mg of IgG/mL, respectively). The colostrometer reading was lower in 1FT samples compared with fresh and 2FT samples. Multiple FT cycles had no effect on nD or %Brix reading. In fresh samples, IgG concentration was moderately correlated with nD (r=0.79), %Brix (r=0.79), and colostrometer reading (r=0.79). Diagnostic test characteristics using the recommended cut point of 1.35966 nD resulted in similar sensitivities for 1FT and 2 FT samples (94.87 and 94.74%, respectively). Cut points of 18 and 19% Brix resulted in the greatest sensitivities (92.31 and 84.62%) and specificity (94.74 and 94.74%, respectively). The 18% Brix cut point resulted in 94.83% of the samples being correctly classified based on IgG concentration. These data support the use of digital refractometer to accurately and rapidly determine IgG concentration in fresh Jersey colostrum. Additionally, these data suggest that IgG concentration determined by RID is affected by multiple FT cycles, whereas estimates obtained by refractometer are not affected by multiple FT cycles.

A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs.

Although variation in the KIT gene is a common cause of white spotting among domesticated animals, KIT has not been implicated in the diverse white spotting observed in the dog. Here, we show that a loss-of-function mutation in KIT recapitulates the coat color phenotypes observed in other species. A spontaneous white spotting observed in a pedigree of German Shepherd dogs was mapped by linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15). DNA sequence analysis identified a novel 1-bp insertion in the second exon that co-segregated with the phenotype. The expected frameshift and resulting premature stop codons predicted a severely truncated c-Kit receptor with presumably abolished activity. No dogs homozygous for the mutation were recovered from multiple intercrosses (P = 0.01), suggesting the mutation is recessively embryonic lethal. These observations are consistent with the effects of null alleles of KIT in other species.

DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters.

Methylation of CpG islands is associated with transcriptional silencing and the formation of nuclease-resistant chromatin structures enriched in hypoacetylated histones. Methyl-CpG-binding proteins, such as MeCP2, provide a link between methylated DNA and hypoacetylated histones by recruiting histone deacetylase, but the mechanisms establishing the methylation patterns themselves are unknown. Whether DNA methylation is always causal for the assembly of repressive chromatin or whether features of transcriptionally silent chromatin might target methyltransferase remains unresolved. Mammalian DNA methyltransferases show little sequence specificity in vitro, yet methylation can be targeted in vivo within chromosomes to repetitive elements, centromeres and imprinted loci. This targeting is frequently disrupted in tumour cells, resulting in the improper silencing of tumour-suppressor genes associated with CpG islands. Here we show that the predominant mammalian DNA methyltransferase, DNMT1, co-purifies with the retinoblastoma (Rb) tumour suppressor gene product, E2F1, and HDAC1 and that DNMT1 cooperates with Rb to repress transcription from promoters containing E2F-binding sites. These results establish a link between DNA methylation, histone deacetylase and sequence-specific DNA binding activity, as well as a growth-regulatory pathway that is disrupted in nearly all cancer cells.

The Use of Contextual Information for Anticipation of Badminton Shots in Different Expertise Levels.

Purpose: The current study investigated the use of contextual information for anticipation in badminton. Method: Participants were groups of elites (n = 26), competitive (n = 15) and novice players (n = 17) whose anticipation accuracy and reaction time were assessed using an ecologically valid badminton specific video-based occlusion test. Two conditions were presented, where either only kinematic information was available (Last Strokes condition, LS), or kinematic and contextual information were both available (Full Rally condition, FR). Results: Participants reacted slower in the FR condition, while no differences in accuracy were observed between the two conditions. Furthermore, all participants were better at side predictions than length, and elites outperformed novices in both side and length predictions. Among the elite group (which was split into adult elites, adult sub-elites & young elites), adult elite athletes showed faster responses for both the LS and FR conditions compared to their other elite counterparts who were much slower in both conditions. Conclusion: These results indicate that even at the highest level, anticipation performance can discriminate between groups of expert performers. In addition, the findings of this study indicate that the role of contextual information might not be as large as hypothesized, and further research is needed to clarify the role of contextual information toward anticipation.

A Comparative Study of Skimmed Milk and Cassava Flour on the Viability of Freeze-Dried Lactic Acid Bacteria as Starter Cultures for Yogurt Fermentation.

The purpose of this study was to evaluate the survival rates and fermentation performance of three freeze-dried lactic acid bacterial cultures previously isolated from Ghanaian traditional fermented milk. LAB cultures, i.e., Lactobacillus delbrueckii, Lactococcus lactis and Leuconostoc mesenteroides, were frozen in the chamber of a Telstar (Lyoquest) laboratory freeze dryer for 10 h at -55 °C (as single and combined cultures) using skimmed milk and cassava flour as cryoprotectants held in plastic or glass cryovials. For viability during storage, freeze-dried LAB cultures were stored in a refrigerator (4 °C) and at room temperature (25 °C) for 4 weeks. The survival of freeze-dried cultures was determined by growth kinetics at 600 nm (OD600). The performance of freeze-dried LAB cultures after 4 weeks of storage was determined by their growth, acidification of milk during yogurt fermentation and consumer sensory evaluation of fermented milk using a nine-point hedonic scale. The survival rates for LAB ranged between 60.11% and 95.4% following freeze-drying. For single cultures, the highest survival was recorded for Lactobacillus delbrueckii (L12), whereas for combined cultures, the highest survival was observed for Lactococcus lactis (L3) combined with Lactobacillus delbrueckii (L12). The consumer acceptability results showed that yogurts produced from a combined starter culture of Lactococcus lactis and Lactobacillus delbrueckii or from a single culture of Lactococcus lactis were the most preferred products with Lactococcus lactis and Lactobacillus delbrueckii possessing high survival rates and high consumer acceptability in yogurt production. These findings are crucial and can be adopted for large-scale production and commercialization of yogurt.

Improved neuropsychological and neurological functioning across three antiretroviral regimens in diverse resource-limited settings: AIDS Clinical Trials Group study a5199, the International Neurological Study.

BACKGROUND: AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. METHODS: Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. RESULTS: The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). CONCLUSIONS: The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. CLINICAL TRIALS REGISTRATION: NCT00096824.