Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death ...following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.
Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.
There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10
), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0×10
). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded
repeats was shorter than in those without expanded
repeats (p = 5.0×10
).
Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.
Please cite this paper as: Cooper K, Lee A, Chien P, Raja E, Timmaraju V, Bhattacharya S. Outcomes following hysterectomy or endometrial ablation for heavy menstrual bleeding: retrospective analysis ...of hospital episode statistics in Scotland. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03011.x
Objective To determine the risk of further gynaecological surgery and gynaecological cancer following hysterectomy and endometrial ablation in women with heavy menstrual bleeding.
Design Population‐based retrospective cohort study.
Setting Scottish hospitals between 1989 and 2006.
Population or sample Scottish women treated with hysterectomy or endometrial ablation for heavy menstrual bleeding between 1989 and 2006.
Methods Anonymised data collected by the Scottish Information Services Division were analysed using appropriate methods across the hysterectomy and endometrial ablation groups. Cox proportional hazards regression analysis was used to examine the survival experience for different surgical outcomes after adjustment for age, year of primary operation and Carstairs quintile.
Main outcome measures Further gynaecological surgery and gynaecological cancer in women.
Results A total of 37 120 women had a hysterectomy, 11 299 women underwent endometrial ablation without a subsequent hysterectomy and 2779 women underwent endometrial ablation followed by a subsequent hysterectomy. The median (interquartile range) duration of follow‐up was 11.6 years (7.9, 14.8) and 6.2 years (2.7, 10.8) in the hysterectomy and endometrial ablation (without hysterectomy) cohorts, respectively. Compared with women who underwent hysterectomy, those who underwent ablation were less likely to need pelvic floor repair adjusted hazards ratio, 0.62; 95% confidence interval (95% CI), 0.50, 0.77 or tension‐free vaginal tape surgery for stress urinary incontinence (adjusted hazards ratio, 0.55; 95% CI, 0.41, 0.74). Abdominal hysterectomy was associated with a lower chance than vaginal hysterectomy of pelvic floor repair surgery (hazards ratio, 0.54; 95% CI, 0.45, 0.64). Overall, the number of women diagnosed with cancer was small, the largest group being breast cancer (n = 584, 1.57% and n = 130, 1.15% in the hysterectomy and endometrial ablation groups respectively; adjusted hazards ratio, 1.14; 95% CI, 0.93–1.39).
Conclusions Hysterectomy is associated with a higher risk than endometrial ablation of surgery for pelvic floor repair and stress urinary incontinence. Surgery for pelvic floor prolapse is more common after vaginal than abdominal hysterectomy.
During mitosis in budding yeast the nucleus first moves to the mother-bud neck and then into the neck. Both movements depend on interactions of cytoplasmic microtubules with the cortex. We ...investigated the mechanism of these movements in living cells using video analysis of GFP-labeled microtubules in wild-type cells and in EB1 and Arp1 mutants, which are defective in the first and second steps, respectively. We found that nuclear movement to the neck is largely mediated by the capture of microtubule ends at one cortical region at the incipient bud site or bud tip, followed by microtubule depolymerization. Efficient microtubule interactions with the capture site require that microtubules be sufficiently long and dynamic to probe the cortex. In contrast, spindle movement into the neck is mediated by microtubule sliding along the bud cortex, which requires dynein and dynactin. Free microtubules can also slide along the cortex of both bud and mother. Capture/shrinkage of microtubule ends also contributes to nuclear movement into the neck and can serve as a backup mechanism to move the nucleus into the neck when microtubule sliding is impaired. Conversely, microtubule sliding can move the nucleus into the neck even when capture/shrinkage is impaired.
We describe the on-state performance of trench oxide-protected SiC UMOSFETs on 115-μm-thick n-type 4H-SiC epilayers designed for blocking voltages up to 14 kV. An on-state current density of 137 A/cm ...2 and specific on-resistance of 228 m/spl Omega//spl middot/cm 2 are achieved at a gate bias of 40 V (oxide field of 2.67 MV/cm). The effect of current spreading on the specific on-resistance for finite-dimension devices is investigated, and appropriate corrections are made.
To document changes in the prevalence of resistance of Propionibacterium acnes to antibiotics used for treating acne.
MEDLINE and EMBASE were searched for publications on P. acnes resistance to ...systemic antibiotics. The search strategy mapped "acne" or "acne vulgaris" with the terms "antibiotic resistance" or "drug resistance, microbial". Only papers published in English during 1976 to 1997 were included in the search.
53 publications met the search criteria. The search output was refined by selecting papers that specifically addressed P. acnes resistance patterns. Additional studies (not included in the search output) were identified from review articles and references of the retrieved articles. Twelve articles were reviewed.
Data on the prevalence of antibiotic-resistant propionibacteria, the incidence of individual resistance phenotypes, mixed resistance, and correlation between poor therapeutic response and resistant propionibacteria were extracted.
Research since 1978 has suggested an association between poor therapeutic response and antibiotic-resistant propionibacteria. The overall incidence of P. acnes antibiotic resistance has increased from 20% in 1978 to 62% in 1996. Resistance to specific antibiotics varied and was most commonly reported with erythromycin and clindamycin, tetracycline and doxcycline, and trimethoprim. Resistance to minocycline is rare.
In many patients with acne, continued treatment with antibiotics can be inappropriate or ineffective. It is important to recognise therapeutic failure and alter treatment accordingly. The use of long-term rotational antibiotics is outdated and will only exacerbate antibiotic resistance.
The Cassini Imaging Science Subsystem acquired high-resolution imaging data on the outer Saturnian moon, Phoebe, during Cassini's close flyby on 11 June 2004 and on Iapetus during a flyby on 31 ...December 2004. Phoebe has a heavily cratered and ancient surface, shows evidence of ice near the surface, has distinct layering of different materials, and has a mean density that is indicative of an ice-rock mixture. Iapetus's dark leading side (Cassini Regio) is ancient, heavily cratered terrain bisected by an equatorial ridge system that reaches 20 kilometers relief. Local albedo variations within and bordering Cassini Regio suggest mass wasting of ballistically deposited material, the origin of which remains unknown.
Geohelminth infections are major parasitic infections with a worldwide distribution. Immunoglobulin E (IgE) is considered to play a central role in protective immunity against these parasites ...although the evidence from experimental animal models infected with helminth parasites and treated with anti-IgE antibodies and from observational studies in human populations of the immunologic correlates of protective immunity against helminths do not support a critical role for IgE in mediating protection against helminths. Anti-IgE treatment of human allergic disorders using a humanized monoclonal IgE antibody (omalizumab, Xolair) has been approved for clinical use in the USA and Europe and there is concern that this treatment may be associated with increased morbidity in populations exposed to helminth infections. A recently published randomized controlled trial investigating the risk of geohelminth infections in allergic patients receiving omalizumab in Brazil has provided some evidence that omalizumab may not be associated with increased morbidity attributable to these parasites. This review examines the evidence for a role of IgE in protective immunity against helminth parasites, discusses the findings of the randomized controlled trial, assesses the potential risks and provides recommendations for anti-IgE treatment in groups of allergic patients with different exposure risks for helminth infections.
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