NHS waiting lists and evidence of national or local failure: analysis of health service data.

OBJECTIVES: To investigate the national distribution of prolonged waiting for elective day case and inpatient surgery, and to examine associations of prolonged waiting with markers of NHS capacity, activity in the independent sector, and need. SETTING: NHS hospital trusts in England. POPULATION: People waiting for elective treatment in the specialties of general surgery; ear, nose and throat surgery; ophthalmic surgery; and trauma and orthopaedic surgery. MAIN OUTCOME MEASURE: Numbers of people waiting six months or longer (prolonged waiting). Characteristics of trusts with large numbers waiting six months or longer were examined by using logistic regression. RESULTS: The distribution of numbers of people waiting for day case or elective surgery in all the specialties examined was highly positively skewed. Between 52% and 83% of patients waiting longer than six months in the specialties studied were found in one quarter of trusts, which in turn contributed 23-45% of the national throughput specific to the specialty. In general, there was little evidence to show that capacity (measured by numbers of operating theatres, dedicated day case theatres, available beds, and bed occupancy rate) or independent sector activity were associated with prolonged waiting, although exceptions were noted for individual specialties. There was consistent evidence showing an increase in prolonged waiting, with increased numbers of anaesthetists across all specialties and with increased bed occupancy rates for ear, nose and throat surgery. Markers of greater need for health care, such as deprivation score and rate of limiting long term illness, were inversely associated with prolonged waiting. CONCLUSION: In most instances, substantial numbers of patients waiting unacceptably long periods for elective surgery were limited to a small number of hospitals. Little and inconsistent support was found for associations of prolonged waiting with markers of capacity, independent sector activity, or need in the surgical specialties examined

Family Planning Decisions, Perceptions and Gender Dynamics among Couples in Mwanza, Tanzania: A Qualitative Study.

Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18-49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Four themes emerged during the study. First, "risks and costs" which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, "male involvement" as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, "gender relations and communication" as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, "urban-rural differences", life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use

Screening of DUB activity and specificity by MALDI-TOF mass spectrometry

Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to quantify in vitro DUB enzyme activity using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Unlike other current assays, this method uses unmodified substrates, such as diubiquitin topoisomers. By analyzing 42 human DUBs against all diubiquitin topoisomers we provide an extensive characterization of DUB activity and specificity. Our results confirm the high specificity of many members of the OTU and JAMM DUB families and highlight that all USPs tested display low linkage selectivity. We also demonstrate that this assay can be deployed to assess the potency and specificity of DUB inhibitors by profiling 11 compounds against a panel of 32 DUBs

A rare presentation of cervical fibroid in pregnancy

Pregnancy in a fibroid uterus is not rare. However cervical fibroid is rare in pregnancy and has unique management challenges. We report a case of cervical fibroid in a Gravida2 Para1 patient that was found incidentally in a routine ultrasound in the second trimester. The fibroid grew in pregnancy till term, caused obstructed labour, a Cesarean section was required for the baby. Post surgery the fibroid prolapsed out of the introitus. Conservative  management was decided to prevent surgical complications, delayed consequences of surgery and to preserve future child bearing. The case shows that conservative management over surgery is sometimes the appropriate choice.Keywords: Cervical fibroid, conservative management, pregnanc

LC determination of propylene glycol in human plasma after pre-column derivatization with benzoyl chloride

A simple high-performance liquid chromatographic method, using photodiode array detection was developed for the determination of propylene glycol in human plasma and in the fluid retreived after continuous veno-venous hemofiltration. The method entailed alkaline derivatization with benzoyl chloride and ethylene glycol as internal standard. The separation of the compounds, after extraction with pentane, was carried out on a Pursuit C8 column with UV-detection at 230 nm. Validation samples were analyzed with an accuracy between 95 and 105%, and intra- and inter-day coefficients of variation of less than 8%. The calibration curve was linear over a concentration range of 5-100 mg

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

International audienc

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness

BACKGROUND: Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with an aim to provide detailed clinical characteristics of renal angiomyolipoma among patients with TSC. METHODS: Patients of any age with a documented clinic visit for TSC within 12 months or who were newly diagnosed with TSC before participation in the registry were eligible. Data specific to renal angiomyolipoma included physical tumour characteristics (multiple, bilateral, lesion size and growing lesions), clinical signs and symptoms, and management. The effects of age, gender and genotype on the prevalence of renal angiomyolipoma were also evaluated. RESULTS: Renal angiomyolipoma was reported in 51.8% of patients at baseline, with higher frequency in female patients (57.8% versus 42.2%). The median age at diagnosis was 12 years. Prevalence of angiomyolipoma was higher in patients with TSC2 compared with TSC1 mutations (59.2% versus 33.3%, P 3 cm in 34.3% of patients. Most patients were asymptomatic (82%). Frequently reported angiomyolipoma-related symptoms included bleeding, pain, elevated blood pressure and impaired renal function. Embolization and mammalian target of rapamycin inhibitors were the two most common treatment modalities. CONCLUSIONS: The TOSCA registry highlights the burden of renal angiomyolipoma in patients with TSC and shows that renal manifestations are initially asymptomatic and are influenced by gender and genotype. Furthermore, the occurrence of significant problems from angiomyolipoma in a minority of younger patients suggests that surveillance should begin in infancy or at initial diagnosis