Sleep in people with and without intellectual disabilities: a systematic review and meta-analysis.

BACKGROUND: Sleep problems are regularly reported in people with intellectual disabilities. Recent years have seen a substantial increase in studies comparing sleep in people with intellectual disabilities to control participants, with an increase in the use of validated, objective measures. Emerging patterns of differences in sleep time and sleep quality warrant pooled investigation. METHODS: A systematic search was conducted across three databases (Ovid Embase, PsycInfo and Medline) and returned all papers comparing sleep in people with intellectual disabilities to a control group, published since the last meta-analysis on the topic. A quality framework was employed to rate the risk of bias across studies. Separate meta-analyses of sleep duration and sleep quality were conducted. Subgrouping compared findings for those studies with participants with genetic syndromes or neurodevelopmental conditions and those with heterogeneous intellectual disability. RESULTS: Thirteen new papers were identified and combined with those from the previous meta-analysis to provide 34 papers in total. Quality of studies was generally rated highly, though sampling provided risk of bias and adaptive functioning was rarely measured. People with intellectual disability associated with genetic syndromes or neurodevelopmental conditions sleep for shorter time periods (standardised mean difference = .26) and experience worse sleep quality (standardised mean difference = .68) than their peers. People with intellectual disability of heterogeneous origin show no difference in sleep time but have poorer sleep quality. There was some evidence that age moderated these effects. CONCLUSIONS: People with intellectual disability have poorer sleep than those without. Subtle patterns suggest that aetiology of intellectual disability moderates the topography of these difficulties, with further work needed to differentiate common and distinct mechanisms across groups.

Distal urethral carcinoma: Contemporary management with phallus preserving techniques.

INTRODUCTION: Primary urethral carcinoma is a rare clinical entity with an incidence of 1 case per million in the United Kingdom. Cancers of the distal urethra are most commonly of squamous subtype and often associated with Human Papilloma Virus infection. Penile preserving techniques are recommended in tumours of the pendulous urethra with a number of surgical approaches described. Herein, we describe the surgical management of 7 patients presenting with primary urethral carcinoma. METHODS: Seven patients diagnosed with primary urethral carcinoma of the distal urethra were identified using a prospectively maintained penile cancer database at our institution from May 2017 to November 2020. RESULTS: The mean age at presentation was 56.5 (33-80) years. Presenting symptoms included visible lesion, LUTS and a groin mass. Three patients had lesions located within the glanular urethra and had a distal urethrectomy and primary closure. Two patients with lesions extending proximal to the glanular urethra and into or beyond the fossa navicularis had a distal urethrectomy with a hypospadic neomeatus formation. One patient with tumour extending into the glans penis underwent distal urethrectomy and partial glansectomy with split thickness skin graft. A partial penectomy was performed for one patient with urethral tumour invading the corporal heads. Mean follow-up was 23.4 (±17.0) months. There have been no disease recurrences to date. CONCLUSION: Penile preserving techniques are feasible in patients with tumours of the pendulous urethra and do not appear to compromise local control.

The 100 Citation Classics in the Irish Medical Literature; A Bibliometric Analysis.

Identifying citation classics is a valuable metric of research performance. Ireland has a distinguished history of medical research, although Ireland's top-cited articles are unknown. The SCOPUS database identified all medical and surgical articles published by journals in the Republic of Ireland or Northern Ireland. The 100 top-cited articles were analysed. The most cited article received 240 citations. There is an observed trend of increasing number of authors over time (p<0.05). General medicine and public health are the most common topics. The majority of works originate from Irish institutions. Collaborative research and non-Irish research are poorly represented among the citation classics. The Irish medical literature contains multiple highly cited and influential articles.

Perspectives from Young South African and Zimbabwean Women on Attributes of Four (Placebo) Vaginal Microbicide Delivery Forms.

INTRODUCTION: Incorporating end-user input into the design of new vaginal microbicides for women is key to optimizing their uptake, consistent use, and, ultimately, success in combatting the heterosexual HIV epidemic. METHODS: The Quatro Study assessed four placebo forms of vaginally inserted HIV-microbicides among young microbicide-naïve African women: on-demand film, insert and gel, and monthly ring. Participants randomly used each product for 1 month and provided product satisfaction ratings (1-5 scale), and opinions on product attributes and potential alternative designs. Qualitative data were collected through focus group discussions at study exit. Multivariable associations between attribute opinions and overall product rating were examined using Poisson regression models with robust standard errors to assess the attributes most influential to satisfaction. RESULTS: Overall opinions of products and their individual attributes were generally positive; all products were rated either 4 or a 5 by ≥ 50% of participants. Attributes related to ease of use and interference with normal activities were the most salient predictors of satisfaction. Preferences for duration of use tended toward relatively shorter use periods for the ring (i.e., 1-3 months vs. 12 months) and for coitally independent dosing for the on-demand products. CONCLUSIONS: How well a product fit in with participants' lifestyles was important to their overall satisfaction. For on-demand products, greater flexibility around timing of use was desired, to avoid coital dependency of the dosing.

Surfaces that Adhesively Discriminate Breast Epithelial Cell Lines and Lymphocytes in Buffer and Human Breast Milk.

We report new surface coatings that adhesively distinguish three breast epithelial cell lines (MCF-10A, MCF-7, and TMX2-28) when cell suspensions in buffer or breast milk are flowed over the coatings. We also report the selective capture of epithelial cells and rejection of Jurkat lymphocytes, with average selectivities exceeding 60 and captured cell purities often exceeding >99%. The surfaces achieve the dual goals of selective cell capture and resistance to fouling by proteins and other components of breast milk. The coatings do not rely on antibody targeting of cell surface markers but instead contain polycation chains embedded within a layer of end-tethered poly(ethylene glycol) (PEG) chains. The PEG, somewhat shielding the polycations, prevents surface fouling by proteins, nondesired cells, and other milk components, while the polycations produce electrostatic attractions that are heterogeneous on nanoscopic length scales. These electrostatic heterogeneities on the engineered coating, shown to produce curvature-selective particle capture in other studies, produce cell selectivity here. The ability of the engineered surfaces to discriminate these cell lines via an electrostatic driving force is remarkable, as the cells are of very similar surface charge as evidenced by their nearly identical ζ-potentials. The current surfaces, which likely distinguish cells based on their electrostatic surface landscape combined with other factors, adhesively distinguish cell lines that may differ only slightly in their expression of a surface marker, or cancer cells that minimally express EpCAM but which have different distributions of electrostatic charge on their surfaces. These surfaces are among the first to be documented for the compatibility of a polymer brush with human breast milk and may find use in technologies that capture cells from human breast milk or other complex fluids for cancer risk assessment.

Selective Adhesive Cell Capture without Molecular Specificity: New Surfaces Exploiting Nanoscopic Polycationic Features as Discrete Adhesive Units.

This work explored how molecularly non-specific polycationic nanoscale features on a collecting surface control kinetic and selectivity aspects of mammalian cell capture. Key principles for selective collector design were demonstrated by comparing the capture of two closely related breast cancer cell lines: MCF-7 and TMX2-28. TMX2-28 is a tamoxifen-selected clone of MCF-7. The collector was a silica surface, negatively-charged at pH 7.4, containing isolated molecules (~ 8 nm diameter) of the cationic polymer, poly(dimethyl-aminoethylmethacrylate), pDMAEMA. Important in this work is the non-selective nature of the pDMAEMA interactions with cells: pDMAEMA generally adheres negatively charged particles and cells in solution. We show here that selectivity towards cells results from collector design: this includes competition between repulsive interactions involving the negative silica and attractions to the immobilized pDMAEMA molecules, the random pDMAEMA arrangement on the surface, and the concentration of positive charge in the vicinity of the adsorbed pDMAEMA chains. The latter act as nanoscopic cationic surface patches, each weakly attracted to negatively-charged cells. Collecting surfaces engineered with an appropriate amount pDMAEMA, exposed to mixtures of MCF-7 and TMX2-28 cells preferentially captured TMX2-28 with a selectivity of 2.5. (This means that the ratio of TMX2-28 to MCF cells on the surface was 2.5 times their compositional ratio in free solution.) The ionic strength-dependence of cell capture was shown to be similar to that of silica microparticles on the same surfaces. This suggests that the mechanism of selective cell capture involves nanoscopic differences in the contact areas of the cells with the collector, allowing discrimination of closely related cell line-based small scale features of the cell surface. This work demonstrated that even without molecular specificity, selectivity for physical cell attributes produces adhesive discrimination.

The Hidden Burden of Outpatient Repeat PSA Testing in a Prospective Cohort.

PSA testing is widespread throughout Europe for diagnostic purposes and follow up. We performed a prospective outpatient cohort study of 250 men (2013-2015) in two hospital sites. Included were those men being followed up by urology with PSA blood testing. First appointments and those men in whom non-PSA tests were ordered by urology were excluded. The median age was 67.2yrs (46-88). Eighty-one point two percent of samples had a combination of 21 different serology tests at an added cost of >€18,000. Abnormal serology resulted in 53 referrals. Twenty-six-six percent of correspondence referenced abnormal serology other than PSA. Follow up of non-PSA test results poses a challenge in an outpatient setting with failure to appropriately follow-up on abnormal results, increased costs, and medico-legal implications. There is currently no Irish legislature in place to safeguard hospital physicians. This study quantifies the levels of expenditure, resources and risk associated with ambulant PSA testing.

The effect of body mass index at diagnosis on clinical outcome in children with newly diagnosed acute lymphoblastic leukemia.

The impact of body mass index (BMI) at diagnosis on treatment outcome in children with acute lymphoblastic leukemia (ALL) is controversial. We studied 373 children with ALL enrolled on the Total XV study, which prospectively used minimal residual disease (MRD) for risk assignment. MRD on day 19 and at the end of remission induction (day 46), cumulative incidence of relapse/refractory disease (CIR), event-free survival (EFS) and overall survival (OS) were evaluated using sets of four, three and two subgroups based on BMI at diagnosis, along with BMI percentile change during remission induction. Higher BMI was associated with older age and higher treatment risk. There was no association between MRD on days 19 or 46 and BMI for four, three or two BMI subgroups (P>0.1 in all cases), nor was BMI associated with CIR or EFS. Obese patients had worse OS compared with non-obese (P=0.031) due to treatment-related mortality and less salvage after refractory disease or bone marrow relapse. No association between BMI change during remission induction and MRD, CIR, EFS or OS was seen. BMI at diagnosis does not predict poorer response or relapse in a contemporary MRD-directed ALL regimen. Improvements in supportive care and innovative, less-toxic frontline/salvage therapies are needed, especially for obese patients.

Ozone production chemistry in the presence of urban plumes.

Ozone pollution affects human health, especially in urban areas on hot sunny days. Its basic photochemistry has been known for decades and yet it is still not possible to correctly predict the high ozone levels that are the greatest threat. The CalNex_SJV study in Bakersfield CA in May/June 2010 provided an opportunity to examine ozone photochemistry in an urban area surrounded by agriculture. The measurement suite included hydroxyl (OH), hydroperoxyl (HO2), and OH reactivity, which are compared with the output of a photochemical box model. While the agreement is generally within combined uncertainties, measured HO2 far exceeds modeled HO2 in NOx-rich plumes. OH production and loss do not balance as they should in the morning, and the ozone production calculated with measured HO2 is a decade greater than that calculated with modeled HO2 when NO levels are high. Calculated ozone production using measured HO2 is twice that using modeled HO2, but this difference in calculated ozone production has minimal impact on the assessment of NOx-sensitivity or VOC-sensitivity for midday ozone production. Evidence from this study indicates that this important discrepancy is not due to the HO2 measurement or to the sampling of transported plumes but instead to either emissions of unknown organic species that accompany the NO emissions or unknown photochemistry involving nitrogen oxides and hydrogen oxides, possibly the hypothesized reaction OH + NO + O2 → HO2 + NO2.

Evidence for NO(x) control over nighttime SOA formation.

Laboratory studies have established a number of chemical pathways by which nitrogen oxides (NO(x)) affect atmospheric organic aerosol (OA) production. However, these effects have not been directly observed in ambient OA. We report measurements of particulate organic nitrates in Bakersfield, California, the nighttime formation of which increases with NO(x) and is suppressed by high concentrations of organic molecules that rapidly react with nitrate radical (NO(3))--evidence that multigenerational chemistry is responsible for organic nitrate aerosol production. This class of molecules represents about a third of the nighttime increase in OA, suggesting that most nighttime secondary OA is due to the NO(3) product of anthropogenic NO(x) emissions. Consequently, reductions in NO(x) emissions should reduce the concentration of organic aerosol in Bakersfield and the surrounding region.

Distribution study of orally administered lipoic acid in rat brain tissues.

Lipoic acid (LA), an essential cofactor for mitochondrial enzymes and a natural antioxidant, has been explored for the treatment of Alzheimer's disease. However, lipoic acid distribution in brain has not been investigated via oral dosing in human subjects or animals. Therefore, we aim to investigate the distribution of orally administered LA from systemic circulation into rat brain tissues and understand the transport efficiency of lipoic acid across the blood-brain barrier. Brain and blood samples were obtained from male Lister Hooded rats at pre-defined time points after single and chronic oral dosing of LA at 50 mg/kg. Levels of LA were determined using liquid chromatography tandem mass spectrometry. An equilibrium dialysis method was employed to elucidate LA protein binding in brain and blood tissues. Basal endogenous levels of LA in control rats were found to fluctuate between 0.005 and 0.267 microM in blood and 0-0.024 microM in brain after correction for residual blood volume. Pharmacokinetic profiling demonstrated rapid biphasic elimination of LA in blood and poor distribution into various brain regions with levels ranging from 0.0009 to 0.0072 microM. The in vitro and in vivo LA brain:blood partition ratios were 0.1 and -0.01, respectively. Our results demonstrate for the first time that LA does not cross the blood-brain barrier readily and suggest that the antioxidant effect of LA in brain may not be due to its direct effect in the central nervous system.

Digestion, rumen fermentation and circulating concentrations of insulin, growth hormone and IGF-1 in steers fed diets based on different proportions of maize silage and grass silage.

Replacing grass silage with maize silage results in a fundamental change in the ratio of structural to non-structural carbohydrates with commensurate changes in rumen fermentation patterns and nutrient utilisation. This study investigated the effects of feeding four forage mixtures, namely grass silage (G); 67 g/100 g grass silage + 33 g/100 g maize silage (GGM); 67 g/100 g maize silage + 33/100 g grass silage (MMG); maize silage (M) to four ruminally and duodenally canulated Holstein Friesian steers. All diets were formulated to be isonitrogenous (22.4 g N/kg DM) using a concentrate mixture. Dietary dry matter (DM) and organic matter (OM) digestibility increased with ascending maize silage inclusion (P < 0.1) whereas starch and neutral detergent fibre digestibility declined (P < 0.05). Ratio of non-glucogenic to glucogenic precursors in the rumen fluid increased with maize silage inclusion (P < 0.01) with a commensurate reduction in rumen pH (P < 0.05). Mean circulating concentrations of insulin were greatest and similar in diets MMG and GGM, lower in diet M and lowest in diet G (P < 0.01). There were no effects of diet on the mean circulating concentration of growth hormone (GH), or the frequency, amplitude and duration of GH pulses, or the mean circulating concentrations of IGF-1. Increasing levels of DM, OM and starch intakes with the substitution of grass silage with maize silage affected overall digestion, nutrient partitioning and subsequent circulating concentrations of insulin.

The use of drotrecogin alfa (activated) in a patient with recent orthotopic liver transplant.

Drotrecogin alfa has been shown to reduce mortality in severe sepsis. However, it remains unlicensed for use in patients with previous liver transplantation. We report its use in such a case. Prior to administration a risk benefit analysis was performed in line with General Medical Council recommendations. This included being satisfied that no appropriately licensed alternative would better serve the patient's needs and that sufficient evidence existed to demonstrate the safety and efficacy of the drug. Responsibility was taken for prescription, monitoring and follow up. The process was carefully documented and the patient recovered fully with no adverse effects. To date the only published data on the use of drotrecogin alpha in transplant recipients is a case series of three patients. Further published data may encourage review of the licence.

No associations of human pulmonary tuberculosis with Sp110 variants.

BACKGROUND: After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis. METHODS: In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing. RESULTS: No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re-sequencing revealed 13 novel Sp110 variants in the 5'-UTR, exons, and adjacent intronic regions. CONCLUSIONS: Based on the results obtained in this case-control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.

The species Mycobacterium africanum in the light of new molecular markers.

The findings of recent studies addressing the molecular characteristics of Mycobacterium tuberculosis complex isolates have initiated a discussion on the classification of M. africanum, especially of those isolates originating from East Africa (cluster F, subtype II) and displaying phenotypic and biochemical characteristics more similar to those of M. tuberculosis. To further address this question, we analyzed a representative collection of 63 M. tuberculosis complex strains comprising 30 M. africanum subtype I strains, 20 M. africanum subtype II strains, 10 randomly chosen M. tuberculosis isolates, and type strains of M. tuberculosis, M. bovis, and M. africanum for the following biochemical and molecular characteristics: single-nucleotide polymorphisms (SNPs) in gyrB and narGHJI and the presence or absence of RD1, RD9, and RD12. For all molecular markers analyzed, subtype II strains were identical to the M. tuberculosis strains tested. In contrast, the subtype I strains as well as the M. africanum type strain showed unique combinations of SNPs in gyrB and genomic deletions (the absence of RD9 and the presence of RD12), which proves their independence from M. tuberculosis and M. bovis. Accordingly, all subtype I strains displayed main biochemical characteristics included in the original species description of M. africanum. We conclude that the isolates from West Africa were proved to be M. africanum with respect to the phenotypic and genetic markers analyzed, while the isolates from East Africa must be regarded as phenotypic variants of M. tuberculosis (genotype Uganda). We propose the addition of the molecular characteristics defined here to the species description of M. africanum, which will allow clearer species differentiation in the future.

Improved limit on the electron capture decay branch of 176Lu.

We have performed searches for the electron-capture decay branches of 176Lu to the ground state and first excited state of 176Yb. No evidence of either decay mode was observed. From these measurements we have established upper limits on both of these possible branches that are each > 20 times more stringent than the single previously published limit.

Costs of near-miss obstetric complications for women and their families in Benin and Ghana.

This paper estimates the total cost to women and their families associated with a spontaneous vaginal delivery and five types of 'near-miss' obstetric complication in Benin and Ghana, and assesses affordability in relation to household cash expenditure. A retrospective evaluation of costs was carried out among 121 mothers in three hospitals in Ghana. A prospective evaluation of costs was undertaken among 420 pregnant women in two hospitals in Benin. Information was collected on the cost of travel to the facilities and of direct medical and non-medical costs incurred during their stay in hospital. In Benin, costs ranged from an average of 15 US dollars for a spontaneous delivery to 256 US dollars for a near-miss complication caused by dystocia. In Ghana, average costs ranged from 18 US dollars for a spontaneous vaginal delivery to 115 US dollars for a near-miss complication caused by haemorrhage. Medical costs accounted for the largest share of total costs, mainly drugs and medical supplies in Ghana and costs of the delivery and any surgical intervention in Benin. Payments associated with a spontaneous vaginal delivery amounted to at least 2% of annual household cash expenditure in both countries. In the case of severe obstetric complications, costs incurred reached a high of 34% of annual household cash expenditure in Benin. The economic burden of hospital-based delivery care in Ghana and Benin is likely to deter or delay women's use of health services. Should a woman develop severe obstetric complications while in labour, the relatively high costs of hospital care could have a potentially catastrophic impact on the household budget.

Invertebrate responses to the management of genetically modified herbicide-tolerant and conventional spring crops. I. Soil-surface-active invertebrates.

The effects of herbicide management of genetically modified herbicide-tolerant (GMHT) beet, maize and spring oilseed rape on the abundance and diversity of soil-surface-active invertebrates were assessed. Most effects did not differ between years, environmental zones or initial seedbanks or between sugar and fodder beet. This suggests that the results may be treated as generally applicable to agricultural situations throughout the UK for these crops. The direction of the effects was evenly balanced between increases and decreases in counts in the GMHT compared with the conventional treatment. Most effects involving a greater capture in the GMHT treatments occurred in maize, whereas most effects involving a smaller capture were in beet and spring oilseed rape. Differences between GMHT and conventional crop herbicide management had a significant effect on the capture of most surface-active invertebrate species and higher taxa tested in at least one crop, and these differences reflected the phenology and ecology of the invertebrates. Counts of carabids that feed on weed seeds were smaller in GMHT beet and spring oilseed rape but larger in GMHT maize. In contrast, collembolan detritivore counts were significantly larger under GMHT crop management.

Invertebrate responses to the management of genetically modified herbicide-tolerant and conventional spring crops. II. Within-field epigeal and aerial arthropods.

The effects of the management of genetically modified herbicide-tolerant (GMHT) crops on the abundances of aerial and epigeal arthropods were assessed in 66 beet, 68 maize and 67 spring oilseed rape sites as part of the Farm Scale Evaluations of GMHT crops. Most higher taxa were insensitive to differences between GMHT and conventional weed management, but significant effects were found on the abundance of at least one group within each taxon studied. Numbers of butterflies in beet and spring oilseed rape and of Heteroptera and bees in beet were smaller under the relevant GMHT crop management, whereas the abundance of Collembola was consistently greater in all GMHT crops. Generally, these effects were specific to each crop type, reflected the phenology and ecology of the arthropod taxa, were indirect and related to herbicide management. These results apply generally to agriculture across Britain, and could be used in mathematical models to predict the possible long-term effects of the widespread adoption of GMHT technology. The results for bees and butterflies relate to foraging preferences and might or might not translate into effects on population densities, depending on whether adoption leads to forage reductions over large areas. These species, and the detritivore Collembola, may be useful indicator species for future studies of GMHT management.