Microfluidic-based chemical sensors take laboratory analytical protocols and miniaturize them into field-deployable systems for in situ monitoring of water chemistry. Here, we present a prototype ...nitrate/nitrite sensor based on droplet microfluidics that in contrast to standard (continuous phase) microfluidic sensors, treats water samples as discrete droplets contained within a flow of oil. The new sensor device can quantify the concentrations of nitrate and nitrite within each droplet and provides high measurement frequency and low fluid consumption. Reagent consumption is at a rate of 2.8 mL/day when measuring every ten seconds, orders of magnitude more efficient than those of the current state-of-the-art sensors. The sensor’s capabilities were demonstrated during a three-week deployment in a tidal river. The accurate and high frequency data (6% error relative to spot samples, measuring at 0.1 Hz) elucidated the influence of tidal variation, rain events, diurnal effects, and anthropogenic input on concentrations at the deployment site. This droplet microfluidic-based sensor is suitable for a wide range of applications such as monitoring of rivers, lakes, coastal waters, and industrial effluents.
To determine the prevalence of autism spectrum disorder (ASD) in Neurofibromatosis Type 1 (NF1).
Second-phase population-based epidemiologic study using an allcase NF1 registry in a defined UK 4.1 ...million population area. A total of 109 (52.7%) of 207 responders from the initial screening phase were grouped by using the parent-rated Social Responsiveness Scale (SRS) as significant ASD (SRS≥76; n = 32), moderate ASD (SRS ≥ 60<76; n = 29), or non-ASD (SRS <60, n = 48). Twenty-three cases from the significant ASD group, 16 from moderate ASD, and 8 from non-ASD (total n = 47), invited proportionately by random selection, were seen for detailed confirmatory ascertainment. Assessments on Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Scale-Generic, and verbal IQ were combined by using standard Collaborative Program for Excellence in Autism criteria into an ASD categorization for each case (ASD, broad ASD with partial features, non-ASD). A preplanned weighted analysis was used to derive prevalence estimates for the whole population.
Fourteen (29.5%) of 47 showed ASD, 13 (27.7%) broad ASD, and 20 (42.5%) non-ASD. The ASD/broad ASD group showed male predominance (1.7:1.0), but did not differ significantly from the non-ASD group on IQ, age, socioeconomic status, inheritance, physical severity, or education. The population prevalence estimate is 24.9% ASD (95% confidence interval 13.1%-42.1%) and 20.8% broad ASD (95% confidence interval 10.0%-38.1%); a total of 45.7% showing some ASD spectrum phenotype.
Findings indicate high prevalence of ASD in NF1, with implications for clinical practice and further research into NF1 as a single-gene model for autism.
Short Total Synthesis of Ajoene Silva, Filipa; Khokhar, Shaista S.; Williams, Danielle M. ...
Angewandte Chemie (International ed.),
September 17, 2018, Letnik:
57, Številka:
38
Journal Article
Recenzirano
Odprti dostop
We describe a short total synthesis of ajoene, a major biologically active constituent of garlic. The instability of allicin as the only other known alternative starting material has led to the ...development of a reliable procedure for the synthesis of ajoene from simple building blocks that is also suitable for upscale operations.
Making garlic: An efficient total synthesis of ajoene from easily available starting materials is reported. Upscaling of the procedure enabled the synthesis of ajoene in larger amounts.
Neurofibromatosis type 2 (NF2) is a tumour-prone disorder characterised by the development of multiple schwannomas and meningiomas. Prevalence (initially estimated at 1: 200,000) is around 1 in ...60,000. Affected individuals inevitably develop schwannomas, typically affecting both vestibular nerves and leading to hearing loss and deafness. The majority of patients present with hearing loss, which is usually unilateral at onset and may be accompanied or preceded by tinnitus. Vestibular schwannomas may also cause dizziness or imbalance as a first symptom. Nausea, vomiting or true vertigo are rare symptoms, except in late-stage disease. The other main tumours are schwannomas of the other cranial, spinal and peripheral nerves; meningiomas both intracranial (including optic nerve meningiomas) and intraspinal, and some low-grade central nervous system malignancies (ependymomas). Ophthalmic features are also prominent and include reduced visual acuity and cataract. About 70% of NF2 patients have skin tumours (intracutaneous plaque-like lesions or more deep-seated subcutaneous nodular tumours). Neurofibromatosis type 2 is a dominantly inherited tumour predisposition syndrome caused by mutations in the NF2 gene on chromosome 22. More than 50% of patients represent new mutations and as many as one-third are mosaic for the underlying disease-causing mutation. Although truncating mutations (nonsense and frameshifts) are the most frequent germline event and cause the most severe disease, single and multiple exon deletions are common. A strategy for detection of the latter is vital for a sensitive analysis. Diagnosis is based on clinical and neuroimaging studies. Presymptomatic genetic testing is an integral part of the management of NF2 families. Prenatal diagnosis and pre-implantation genetic diagnosis is possible. The main differential diagnosis of NF2 is schwannomatosis. NF2 represents a difficult management problem with most patients facing substantial morbidity and reduced life expectancy. Surgery remains the focus of current management although watchful waiting with careful surveillance and occasionally radiation treatment have a role. Prognosis is adversely affected by early age at onset, a higher number of meningiomas and having a truncating mutation. In the future, the development of tailored drug therapies aimed at the genetic level are likely to provide huge improvements for this devastating condition.
It is frequent for news items to lead to a short lived temporary increase in interest in a particular health related service, however it is rare for this to have a long lasting effect. In 2013, in ...the UK in particular, there has been unprecedented publicity in hereditary breast cancer, with Angelina Jolie's decision to have genetic testing for the BRCA1 gene and subsequently undergo risk reducing mastectomy (RRM), and a pre-release of the NICE guidelines on familial breast cancer in January and their final release on 26th June. The release of NICE guidelines created a lot of publicity over the potential for use of chemoprevention using tamoxifen or raloxifene. However, the longest lasting news story was the release of details of film actress Angelina Jolie's genetic test and surgery.
To assess the potential effects of the 'Angelina Jolie' effect, referral data specific to breast cancer family history was obtained from around the UK for the years 2012 and 2013. A consortium of over 30 breast cancer family history clinics that have contributed to two research studies on early breast surveillance were asked to participate as well as 10 genetics centres. Monthly referrals to each service were collated and increases from 2012 to 2013 assessed.
Data from 12 family history clinics and 9 regional genetics services showed a rise in referrals from May 2013 onwards. Referrals were nearly 2.5 fold in June and July 2013 from 1,981 (2012) to 4,847 (2013) and remained at around two-fold to October 2013. Demand for BRCA1/2 testing almost doubled and there were also many more enquiries for risk reducing mastectomy. Internal review shows that there was no increase in inappropriate referrals.
The Angelina Jolie effect has been long lasting and global, and appears to have increased referrals to centres appropriately.
Abstract
The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the ...European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy.
Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome ...can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (
and Suppressor of fused (
mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in
mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive "rhabdoid" term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in
or, more rarely,
, each of which encodes a chromatin remodeling family member.
mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of
and
mutations.
Because clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2) have not been identified, we aimed to determine whether genotype-phenotype correlations are useful ...in clinical trials in NF1 and NF2.
The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Biomarker Group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumors. The group then met during a series of consensus meetings to develop a joint report.
We found that in NF2, the genetic severity score is clearly of potential clinical use. In NF1, despite over 3,000 constitutional variants having been described in the
gene, only 4 actionable genotype-phenotype correlations exist. The diagnosis and treatment decision of these tumors should ideally include histopathology and compilation of some of the genetic markers.
We summarized emerging clinical use of genotype-phenotype correlations in neurofibromatosis.
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