What is the best approach to goiter in euthyroid patients?

In the absence of outcome studies, experts recommend ultrasound evaluation of nontoxic multinodular goiters (MNG) followed by fine-needle aspiration (FNA) of suspicious nodules (strength of recommendation [SOR]: C, consensus-based guidelines). Thyroid hormone suppression therapyreduces the size of MNG (SOR: A, systematic review of randomized controlled trials [RCTs]), but it risks inducing hyperthyroidism (SOR: C, expert opinion). Experts recommend thyroidectomy for compressive symptoms, progressive growth, or ultrasound or FNA results indicating thyroid cancer (SOR: C, consensus based guidelines). Expert guidelines recommend repeat ultrasound at 6 to 18 months to follow up benign nodules or nonendemic MNG in patients at low risk of malignancy and subsequent follow-up of stable nodules every 3 to 5 years (SOR: C, consensus-based guidelines)

Treatment of HSV infection in late pregnancy

Pregnant women with a primary or recurrent episode of genital HSV infection who are later than 36 weeks of gestation should be treated with acyclovir (Zovirax) or valacyclovir (Valtrex) for viral suppression. (Strength of Recommendation [SOR]: A, based on one systematic review.) Suppressive therapy at the time of delivery can reduce the rate of recurrence, the risk of asymptomatic viral shedding, and the number of cesarean deliveries because of active HSV infection. Women with active lesions at the time of labor should have a cesarean delivery to decrease vertical transmission of HSV. (SOR: B, based on one prospective cohort study.) Acyclovir prophylaxis is more cost-effective than expectant management with cesarean delivery in women with a history of genital HSV infection, with or without recurrence during pregnancy

Evidence Review: Perennial Energy Crops and their Potential in Scotland

The Committee on Climate Change (CCC) have identified that under net zero emissions scenarios, bioenergy supplied in the UK could reach 200TWh (with 170TWh of this sourced from the UK) by 2050. The CCC considered that UK-produced energy crops could be an important source of bioenergy and assumed that around 700,000 ha could be planted in the UK to help achieve this target, although it did not consider where. If it were evenly spread across the arable area of the UK, Scotland’s ‘share’ would be about 70,000 ha. This report examines the potential for a sustainable expansion of perennial bioenergy crop production on low grade agricultural land or underutilised land, focusing on short rotation coppice (SRC), miscanthus and short rotation forestry (SRF)

“It’s a terrible way to go to work:” what 70 million readers’ comments on the Guardian revealed about hostility to women and minorities online

In 2006, the Guardian opened many of its articles to readers’ comments to encourage a “conversation” between journalists and their readers. Readers responded enthusiastically, and by 2016 they had posted 70 million comments on the site. However, from the outset many journalists complained about the quality and tone of comments. Female and BAME (Black, Asian and minority ethnic) journalists in particular complained that they were subject to more abuse than their male, white counterparts. This study finds prima facie evidence to support the journalists’ claims. Using comments that had been blocked by moderators as a proxy for abuse and dismissive trolling, it was found that articles written by women did attract a higher percentage of blocked comments than those written by men, regardless of the subject of the article; this effect was heightened when the articles ran in a particularly male-dominated section of the site. There was also evidence that articles written by BAME writers attracted disproportionate levels of blocked comments, even though the research was not designed to reveal this. Preliminary research findings were published in the Guardian and readers were invited to comment on them. Guardian journalists’ experiences of comments were also surveyed. Both sets of responses are analysed here, in order to explore the contested nature of online abuse in an online news media environment, and to evaluate the potential of comments to “democratise” journalism

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Running wild, running free : capturing, harnessing and disseminating knowledge flows in support of animal health

In June 2002 the Texas A&M University Libraries instituted a new electronic document delivery service called DeliverEdocs. The service uses the Illiad software, presents a single interface to our users uniting previously separate campus library interlibrary loan/document delivery departments, and offers free desktop access to any article, even those found on our own shelves. The system is entirely web-based and users can log on to the system to request or pick up articles in pdf format from any computer with access to the Internet. The TAMU Medical Sciences Library serves the only college of veterinary medicine in the state of Texas, and has a strong commitment to serving animal health practitioners throughout the state. In addition we serve a college of medicine, a unique school of rural public health, and a multitude of agricultural extension stations. Our user population is widespread and seldom able to physically visit the library. To date we have 2,508 registered users of the new system. During the fiscal year 2004 we borrowed 6767 articles on behalf of our users, filling and delivering to the desktop a total of 11,526 requests. While DeliverEdocs has received rave reviews from our users, it has not been without challenges. Providing electronic delivery caused significant impact on staff, especially in redesigned workflows, position descriptions, and user expectations for rapid turn around times. Reduced library traffic and new tasks have resulted in a change in our staffing patterns. Technological issues remain a constant issue from our varied and geographically separate clientele. This poster illustrates the effect of DeliverEdocs on staff and users alike. We also discuss some of the future considerations in maintaining the system and the service.Poster presented at the 5th International Conference of Animal Health Information Specialists, 4-7 July 2005, Onderstepoort, South AfricaBecky McKay, Chris Foster [and] Martha Bedardhttp://www.library.up.ac.za/vet/icahi

Totally E: meeting the challenge of going electronic only for document delivery and interlibrary loan

Abstract only of poster presentationProceedings of the 5th International Conference of Animal Health Information Specialists, 4-7 July 2005: Running wild, running free: capturing, harnessing and disseminating knowledge flows in support of animal health. 2006. pp. 15