Sensitivity to syntax in visual cortex

One of the most intriguing findings on language comprehension is that violations of syntactic predictions can affect event-related potentials as early as 120 ms, in the same time-window as early sensory processing. This effect, the so-called early left-anterior negativity (ELAN), has been argued to reflect word category access and initial syntactic structure building (Friederici, 2002). In two experiments, we used magnetoencephalography to investigate whether (a) rapid word category identification relies on overt category-marking closed-class morphemes and (b) whether violations of word category predictions affect modality-specific sensory responses. Participants read sentences containing violations of word category predictions. Unexpected items varied in whether or not their word category was marked by an overt function morpheme. In Experiment 1, the amplitude of the visual evoked M100 component was increased for unexpected items, but only when word category was overtly marked by a function morpheme. Dipole modeling localized the generator of this effect to the occipital cortex. Experiment 2 replicated the main results of Experiment 1 and eliminated two non-morphology-related explanations of the M100 contrast we observed between targets containing overt category-marking and targets that lacked such morphology. Our results show that during reading, syntactically relevant cues in the input can affect activity in occipital regions at around 125 ms, a finding that may shed new light on the remarkable rapidity of language processing

Routine vestibular function assessment in children with congenital CMV: are we ready?

Congenital cytomegalovirus (cCMV) is a leading non-genetic cause of sensorineural hearing loss (SNHL) and is an important cause of neurodevelopmental delay.1,2 Vestibular hypofunction can result in gross motor delay, hypotonia, postural instability, and lack of spatial awareness. Vestibular physiotherapy and safety advice may be indicated. Studies have shown vestibular impairment to be common in children with cCMV, in both those with, and without, sensorineural hearing loss.3 Routine screening for, and appropriate management of, vestibular hypofunction in all children with hearing loss has been recommended in NICE-accredited guidelines issued by the British Association of Audiovestibular Physicians.4 One author5 has recommended that children with cCMV with and without SNHL be tested for vestibular dysfunction. However, how and when to test vestibular function in children with cCMV does not form part of standard guidance for the management of cCMV in the UK

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Recommendations for Transitioning Young People with Primary Immunodeficiency Disorders and Autoinflammatory Diseases to Adult Care

Purpose: Significant improvements in the prognosis for young patients with Primary Immunodeficiency Diseases (PID) and Autoinflammatory Disorders (AID), which together make up the majority of Inborn Errors of Immunity (IEI), have resulted in the need for optimisation of transition and transfer of care to adult services. Effective transition is crucial to improve health outcomes and treatment compliance among patients. Evaluations of existing transition programmes in European health centres identified the absence of disease-specific transition guidelines for PID and AID, as a challenge to the transition process. This research aimed to establish expert consensus statements for the transition of young patients with PID and AID to adult services. Methods: This project used the Delphi method to establish mutual agreement for the proposed recommendations. A draft set of statements was developed following a literature review of existing transition programmes. Then the ERN RITA Transition Working Group convened to review the drafted recommendations and develop them into a survey. This survey was circulated among healthcare professionals to determine consensus using a five-point Likert scale, with the level of agreement set to 80% or greater. Statements that did not reach consensus were revised by the Working Group and recirculated among respondents. Results: The initial survey received 93 responses from 68 centres across 23 countries, while the following survey outlining revised recommendations received 66 responses. The respondents agreed upon recommendations detailing the structure and administration of transition programmes, collaborative working with social systems, and contraindications to transfer of care. Conclusion: This paper sets out a comprehensive set of recommendations to optimise transitional care for PID and AID

A reference map of the human binary protein interactome.

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes

Ganciclovir treatment in children: evidence of subtherapeutic levels

International audienceGanciclovir is used to treat babies and older children with cytomegalovirus-related disease. Treatment courses are generally derived from adult studies and there are few data relating to pharmacokinetics of ganciclovir in children. In adults low trough ganciclovir levels have been associated with treatment failure and virological resistance. Data on suitable drug levels for use in therapeutic drug monitoring in the paediatric age group do not currently exist