Performance of Hair Testing for Cocaine Use-Comparison of Five Laboratories Using Blind Reference Specimens.

The purpose of this study was to compare results from five commercial hair testing laboratories conducting workplace drug testing with regard to bias, precision, selectivity and decontamination efficiency. Nine blind hair specimens, including cocaine-positive drug user specimens (some contaminated with methamphetamine) and negative specimens contaminated with cocaine, were submitted in up to five replicates to five different laboratories. All laboratories correctly identified cocaine in all specimens from drug users. For an undamaged hair specimen from a cocaine user, within-laboratory Coefficients of Variation (CVs) of 5-22% (median 8%) were reported, showing that it is possible to produce a homogenous proficiency testing sample from drug user hair. Larger CVs were reported for specimens composed of blended hair (up to 29%) and curly/damaged hair (19-67%). Quantitative results appeared to be method-dependent, and the reported cocaine concentrations varied up to 5-fold between the laboratories, making interlaboratory comparisons difficult. All laboratories reported at least one positive result in specimens contaminated with cocaine powder, followed by sweat and shampoo treatments. Benzoylecgonine, norcocaine, cocaethylene and hydroxylated cocaine metabolites were all detected in cocaine powder-contaminated specimens. This indicates that current industry standards for analyzing and reporting positive cocaine results are not completely effective at identifying external contamination. Metabolite ratios between meta- or para-hydroxy-cocaine and cocaine were 6- and 10-fold lower in contaminated specimens compared to those observed in cocaine user specimens, supporting their potential use in distinguishing samples positive due to contamination and drug use.

The Precision Teaching System: A Synthesized Definition, Concept Analysis, and Process.

Precision teaching (PT) has a long history in the fields of behavior analysis and education. As the system of PT has evolved and grown, many developments and discoveries have been made. The current article briefly reviews the history of PT and presents a synthesized definition derived from the unique legacy of the system. The article includes (a) an updated definition of PT, (b) a concept analysis of PT, and (c) a set of synthesized steps that comprise PT. The goal of the current article is to present a succinct summary of the current state of PT for readers from all backgrounds, with examples that encompass the entirety of the applications of PT.

Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations.

Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

Expressed information needs of patients with osteoporosis and/or fragility fractures: a systematic review.

This systematic review identified patients have unmet information needs about the nature of osteoporosis, medication, self-management and follow-up. Clinician knowledge and attitudes appear to be of key importance in determining whether these needs are met. Unmet information needs appear to have psychosocial consequences and result in poor treatment adherence. PURPOSE: Patient education is an integral component of the management of osteoporosis, yet patients are dissatisfied with the information they receive and see this as an area of research priority. This study aimed to describe and summarise the specific expressed information needs of patients in previously published qualitative research. METHODS: Using terms relating to osteoporosis, fragility fracture and information needs, seven databases were searched. Articles were screened using predefined inclusion and exclusion criteria. Full-text articles selected for inclusion underwent data extraction and quality appraisal. Findings were drawn together using narrative synthesis. RESULTS: The search identified 11,024 articles. Sixteen empirical studies were included in the review. Thematic analysis revealed three overarching themes relating to specific information needs, factors influencing whether information needs are met and the impact of unmet information needs. Specific information needs identified included the following: the nature of osteoporosis/fracture risk; medication; self-management and understanding the role of dual energy x-ray absorptiometry and follow-up. Perceived physician knowledge and attitudes, and the attitudes, beliefs and behaviours of patients were important factors in influencing whether information needs were met, in addition to contextual factors and the format of educational resources. Failure to elicit and address information needs appears to be associated with poor treatment adherence, deterioration of the doctor-patient relationship and important psychosocial consequences. CONCLUSION: This is the first study to describe the information needs of patients with osteoporosis and fracture, the impact of this information gap and possible solutions. Further research is needed to co-design and evaluate educational interventions with patients.

Root architecture governs plasticity in response to drought.

AIMS: Root characteristics are important for predicting plant and ecosystem responses to resource scarcity. Simple, categorical traits for roots could be broadly applied to ecosystem function and restoration experiments, but they need to be evaluated for their role and behaviour under various stresses, including water limitation. We hypothesised that more complex root architectures allow more plastic responses to limited water than do tap roots. METHODS: We carried out two greenhouse experiments: one with a range of grassland plant species; the other with only species of Asteraceae to test the responsiveness of root architectural classes to location of limited water in the soil column. Using trait screening techniques and X-ray tomography, we measured the plasticity of the roots in response to water location. RESULTS: Plasticity of root biomass was lowest in tap rooted species, while fibrous and rhizomatous roots allocated biomass preferentially to where the soil was wettest. X-ray tomography indicated that root morphology was least plastic in rhizomatous species. CONCLUSIONS: Our results provide a starting point to effective categorisation of plants in terms of rooting architecture that could aid in understanding drought tolerance of grassland species. They also demonstrate the utility of X-ray tomography in root analyses.

Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol.

INTRODUCTION: Knee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions. METHODS AND ANALYSIS: Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI. ETHICS AND DISSEMINATION: Research ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians. PROSPERO REGISTRATION NUMBER: CRD42017054049.

Vitamin D in obesity.

PURPOSE OF REVIEW: Vitamin D is essential for bone health, and may also have important functions in immunity and other systems. Vitamin D deficiency is common, and testing and supplementation is increasing. Serum vitamin D is lower in obese people; it is important to understand the mechanism of this effect and whether it indicates clinically significant deficiency. RECENT FINDINGS: Vitamin D is fat soluble, and distributed into fat, muscle, liver, and serum. All of these compartments are increased in volume in obesity, so the lower vitamin D likely reflects a volumetric dilution effect and whole body stores of vitamin D may be adequate. Despite lower serum vitamin D, obese adults do not have higher bone turnover or lower bone mineral density. Patients undergoing bariatric surgery do have bone loss, and ensuring vitamin D sufficiency in these patients may help to attenuate bone loss. SUMMARY: Lower vitamin D in obese people is a consistent finding across age, ethnicity, and geography. This may not always reflect a clinical problem. Obese people need higher loading doses of vitamin D to achieve the same serum 25-hydroxyvitamin D as normal weight.

Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health.

BACKGROUND: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone. OBJECTIVE: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight. DESIGN: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health. RESULTS: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people. CONCLUSIONS: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3 We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status.

Cognitive Rehabilitation for Attention and Memory in people with Multiple Sclerosis: study protocol for a randomised controlled trial (CRAMMS).

BACKGROUND: People with multiple sclerosis have problems with memory and attention. Cognitive rehabilitation is a structured set of therapeutic activities designed to retrain an individual's memory and other cognitive functions. Cognitive rehabilitation may be provided to teach people strategies to cope with these problems, in order to reduce the impact on everyday life. The effectiveness of cognitive rehabilitation for people with multiple sclerosis has not been established. METHODS: This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based cognitive rehabilitation programme for attention and memory problems for people with multiple sclerosis. Four hundred people with multiple sclerosis will be randomised from at least four centres. Participants will be eligible if they have memory problems, are 18 to 69 years of age, are able to travel to attend group sessions and give informed consent. Participants will be randomised in a ratio of 6:5 to the group rehabilitation intervention plus usual care or usual care alone. Intervention groups will receive 10 weekly sessions of a manualised cognitive rehabilitation programme. The intervention will include both restitution strategies to retrain impaired attention and memory functions and compensation strategies to enable participants to cope with their cognitive problems. All participants will receive a follow-up questionnaire and an assessment by a research assistant at 6 and 12 months after randomisation. The primary outcome is the Multiple Sclerosis Impact Scale (MSIS) Psychological subscale at 12 months. Secondary outcomes include the Everyday Memory Questionnaire, General Health Questionnaire-30, EQ-5D and a service use questionnaire from participants, and the Everyday Memory Questionnaire-relative version and Carer Strain Index from a relative or friend. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the MSIS Psychological subscale at 12 months will be used to estimate the effect of the group cognitive rehabilitation programme. DISCUSSION: The study will provide evidence regarding the clinical and cost-effectiveness of a group-based cognitive rehabilitation programme for attention and memory problems in people with multiple sclerosis. TRIAL REGISTRATION: ISRCTN09697576 . Registered 14 August 2014.

Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood.

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site-specific differences in BMD, bone structure, or bone strength between obese and normal-weight adults. We studied 100 individually-matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m2) and obese (BMI >30 kg/m2) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual-energy X-ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high-resolution peripheral QCT (HR-pQCT) and micro-finite element analysis. Serum type 1 procollagen N-terminal peptide (P1NP) and collagen type 1 C-telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR-pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age-related bone loss and may increase peak bone mass.

Vitamin D associates with improved quality of life in participants with irritable bowel syndrome: outcomes from a pilot trial.

BACKGROUND: Vitamin D deficiency has been associated or implicated with the pathophysiology of the gastrointestinal conditions inflammatory bowel disease and colorectal cancer, as well as with depression. No trials or epidemiology studies to date have investigated a link with irritable bowel syndrome (IBS). A single case report has suggested a benefit in IBS of vitamin D supplementation. We hypothesised that IBS participants with vitamin D insufficiency would benefit from repletion in terms of their IBS symptoms. We undertook a pilot trial to provide data to support a power calculation and to justify a full trial. METHODS: This was a randomised, double blinded, three-arm parallel design trial of vitamin D, placebo or a combination of vitamin D and probiotics. Participants were further stratified according to whether they were vitamin D replete or insufficient. Vitamin D status was determined by blood test at baseline and exit; IBS symptoms were assessed by validated questionnaire; dietary intakes were assessed by food frequency questionnaire. RESULTS: A significant proportion of the IBS population were vitamin D deficient, such that the replete stratum could not be adequately recruited. There was a significant association in the baseline data between circulating vitamin D level and quality of life ("How much has IBS affected your life?"). Supplementation significantly improved vitamin D level versus placebo. IBS symptoms were not significantly improved in this pilot, although a power calculation was enabled from the intervention data. CONCLUSIONS: The IBS population exhibits significant levels of vitamin D insufficiency and would benefit from screening and possible supplementation. The impact of IBS on quality of life may be reduced by vitamin D level. Future trials should have a sample size of over 97. TRIAL REGISTRATION NUMBER: ICTRN 6116003917.

Clinal distribution of a chromosomal rearrangement: a precursor to chromosomal speciation?

Geographically structured genetic variants provide an effective means to assess sources of natural selection and mechanisms of adaptation to local environments. Correlated selection pressures along environmental gradients favor subdivision of genomes through chromosomal rearrangement. This study examines populations of Drosophila americana to evaluate selection pressures affecting chromosomal forms distinguished by a centromeric fusion. Analyses of chromosomal polymorphism throughout the Mississippi River Valley in the central United States reveal the presence of a distinct latitudinal cline for the chromosomal rearrangement. The cline has a width of 623 km centered at 35.97 degrees N and displays a characteristic sigmoid shape consistent with a balance between selection and dispersal. Extreme low temperature during January, an indicator of winter severity, was identified as the environmental variable that most accurately predicts arrangement frequency. An intriguing relationship identified between the chromosomal cline and operational sex ratio indicates that these alternative arrangements of the X chromosome may influence sex-specific survival. A hypothesis for the cline is presented wherein variation associated with the alternative chromosome forms influences distinct overwintering strategies. The resulting subdivision within the genome embodies a transitory stage of a speciation process in which locally adapted gene complexes provide a foundation for species formation.

Independent origins of new sex-linked chromosomes in the melanica and robusta species groups of Drosophila.

BACKGROUND: Recent translocations of autosomal regions to the sex chromosomes represent important systems for identifying the evolutionary forces affecting convergent patterns of sex-chromosome heteromorphism. Additions to the sex chromosomes have been reported in the melanica and robusta species groups, two sister clades of Drosophila. The close relationship between these two species groups and the similarity of their rearranged karyotypes motivates this test of alternative hypotheses; the rearranged sex chromosomes in both groups are derived through a common origin, or the rearrangements are derived through at least two independent origins. Here we examine chromosomal arrangement in representatives of the melanica and the robusta species groups and test these alternative hypotheses using a phylogenetic approach. RESULTS: Two mitochondrial and two nuclear gene sequences were used to reconstruct phylogenetic relationships of a set of nine ingroup species having fused and unfused sex chromosomes and representing a broad sample of both species groups. Different methods of phylogenetic inference, coupled with concurrent cytogenetic analysis, indicate that the hypothesis of independent origins of rearranged sex chromosomes within each species group is significantly more likely than the alternative hypothesis of a single common origin. An estimate tightly constrained around 8 My was obtained for the age of the rearranged sex chromosomes in the melanica group; however, a more loosely constrained estimate of 10-15 My was obtained for the age of the rearrangement in the robusta group. CONCLUSION: Independent acquisition of new chromosomal arms by the sex chromosomes in the melanica and robusta species groups represents a case of striking convergence at the karyotypic level. Our findings indicate that the parallel divergence experienced by newly sex-linked genomic regions in these groups represents an excellent system for studying the tempo of sex chromosome evolution.

Prevalence of bacterial vaginosis in lesbians and heterosexual women in a community setting.

OBJECTIVES: High prevalence of bacterial vaginosis (BV) has been reported in lesbians but most studies were based in sexually transmitted infection clinic settings; therefore, we wished to determine the prevalence and risk factors of BV in lesbians and heterosexual women in a community setting in the UK. METHODS: A cross-sectional study recruiting lesbian women volunteers from community groups, events, clubs and bars. Heterosexual women were recruited from a community family planning clinic. They self-swabbed to create a vaginal smear, which was Gram-stained and categorised as BV, intermediate or normal flora. They completed a questionnaire about age, ethnic group, smoking, genital hygiene practices and sexual history. RESULTS: Of 189 heterosexuals and 171 lesbians recruited, 354 had gradeable flora. BV was identified in 43 (25.7%) lesbians and 27 (14.4%) heterosexuals (adjusted OR 2.45, 95% CI 1.25 to 4.82; p = 0.009). Concordance of vaginal flora within lesbian partnerships was significantly greater than expected (27/31 (87%) couples, kappa = 0.63; p<0.001). Smoking significantly increased the risk of BV regardless of sexuality (adjusted OR 2.65; p = 0.001) and showed substantial concordance in lesbian partnerships but less than for concordance of flora. CONCLUSIONS: Women who identified as lesbians have a 2.5-fold increased likelihood of BV compared with heterosexual women. The prevalence is slightly lower than clinic-based studies and as volunteers were recruited in community settings, this figure may be more representative of lesbians who attend gay venues. Higher concordance of vaginal flora within lesbian partnerships may support the hypothesis of a sexually transmissible factor or reflect common risk factors such as smoking.

Positive selection near an inversion breakpoint on the neo-X chromosome of Drosophila americana.

Unique features of heteromorphic sex chromosomes are produced as a consequence of sex-linked transmission. Alternative models concerning the evolution of sex chromosomes can be classified in terms of genetic drift or positive selection being the primary mechanism of divergence between this chromosomal pair. This study examines early changes on a newly acquired chromosomal arm of the X in Drosophila americana, which was derived from a centromeric fusion between the ancestral X and previously autosomal chromosome 4 (element B). Breakpoints of a chromosomal inversion In(4)a, which is restricted to the neo-X, are identified and used to guide a sequence analysis along chromosome 4. Loci flanking the distal breakpoint exhibit patterns of sequence diversity consistent with neutral evolution, yet loci near the proximal breakpoint reveal distinct imprints of positive selection within the neo-X chromosomal class containing In(4)a. Data from six separate positions examined throughout the proximal region reveal a pattern of recent turnover driven by two independent sweeps among chromosomes with the inverted gene arrangement. Selection-mediated establishment of an extended haplotype associated with recombination-suppressing inversions on the neo-X indicates a pattern of active coadaptation apparently initiated by X-linked transmission and potentially sustained by intralocus sexual conflict.

Increased nucleotide diversity with transient Y linkage in Drosophila americana.

Recombination shapes nucleotide variation within genomes. Patterns are thought to arise from the local recombination landscape, influencing the degree to which neutral variation experiences hitchhiking with selected variation. This study examines DNA polymorphism along Chromosome 4 (element B) of Drosophila americana to identify effects of hitchhiking arising as a consequence of Y-linked transmission. A centromeric fusion between the X and 4(th) chromosomes segregates in natural populations of D. americana. Frequency of the X-4 fusion exhibits a strong positive correlation with latitude, which has explicit consequences for unfused 4(th) chromosomes. Unfused Chromosome 4 exists as a non-recombining Y chromosome or as an autosome proportional to the frequency of the X-4 fusion. Furthermore, Y linkage along the unfused 4 is disrupted as a function of the rate of recombination with the centromere. Inter-population and intra-chromosomal patterns of nucleotide diversity were assayed using six regions distributed along unfused 4(th) chromosomes derived from populations with different frequencies of the X-4 fusion. No difference in overall level of nucleotide diversity was detected among populations, yet variation along the chromosome exhibits a distinct pattern in relation to the X-4 fusion. Sequence diversity is inflated at loci experiencing the strongest Y linkage. These findings are inconsistent with the expected reduction in nucleotide diversity resulting from hitchhiking due to background selection or selective sweeps. In contrast, excessive polymorphism is accruing in association with transient Y linkage, and furthermore, hitchhiking with sexually antagonistic alleles is potentially responsible.