Cognitive Digital Biomarkers from Automated Transcription of Spoken Language.

BACKGROUND: Although patients with Alzheimer's disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status. OBJECTIVE: To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing. DESIGN: Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses. SETTING: Observational cohort study. PARTICIPANTS: 146 participants in the Framingham Heart Study. MEASUREMENTS: Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions. RESULTS: Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90. CONCLUSIONS: The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.

Gender and health literacy: men's health beliefs and behaviour in Trinidad.

Gender variations in health literacy have implications for engagement in preventive behaviours and the uptake of health services, especially in areas such as the Caribbean where there are marked disparities in life expectancy and health service utilization. A self-reported questionnaire was used to examine men's concepts of health, their help-seeking behaviours and their functional and interactive health literacy. Two hundred and forty-eight men across the life course participated at three sites in Trinidad. Data were analysed using descriptive statistics, with free-text responses analysed thematically. Men were concerned about, and accepted responsibility for their own health but social norms concerning sickness and masculinity were barriers to accessing health services. Almost one-third (31.5%) sought advice from a healthcare service when they were last sick because they were prompted to do so by their wife/partner or family. Levels of functional and interactive health literacy were not high among older men, who were reliant on healthcare professionals to communicate health messages. There was an age divide in e-health literacy. There is little published evidence on men's health literacy, particularly from Caribbean countries such as Trinidad and Tobago. This study highlights the importance of the design and implementation of specific policies focusing on men's health. A major challenge is to engage with men who do not access health services.

Necrotising Scleritis and Peripheral Ulcerative Keratitis Associated with Rheumatoid Arthritis Treated with Rituximab.

Background Rheumatoid arthritis is a chronic and common inflammatory autoimmune disease. This primarily involves the synovia of the joints, but can cause many extra-articular manifestations as well, including peripheral ulcerative keratitis (PUK) and necrotising scleritis. These are often a threat to vision; they significantly compromise not only the eye's structural integrity but are also important for prognosis and need urgent management. History and signs Three cases of peripheral ulcerative keratitis associated with rheumatoid arthritis were recorded in the electronic databank of the Jules Gonin Uveitis Clinic, two with necrotising scleritis and peripheral ulcerative keratitis and one with only peripheral ulcerative keratitis. They were all followed at Jules Gonin Eye Hospital (Lausanne, Switzerland), conjointly with the Department of Rheumatology at the Centre Hospitalier Universitaire Vaudois (Lausanne, Switzerland). Therapy and Outcome Good initial therapeutic response was observed in the two patients who received rituximab therapy. The patient who received only high dose corticosteroid developed massive colon perforation as well as acute renal insufficiency a few days after her ocular event. Conclusion From our limited number of patients, we found that the two patients who received the induction therapy with rituximab were stabilised from an ocular standpoint; however, rituximab had to be switched to other molecules, either due to other systemic symptoms from the disease itself or due to adverse effect of this treatment. This contributes to the increasing number of reports that rituximab can be an effective treatment for refractory ocular complications of rheumatoid arthritis (RA), at least as an induction therapy.

Trials and tribulations: how we established a major incident database.

OBJECTIVE: We describe the process of setting up a database of major incident reports and its potential future application. METHOD: A template for reporting on major incidents was developed using a consensus-based process involving a team of experts in the field. A website was set up as a platform from which to launch the template and as a database of submitted reports. This paper describes the processes involved in setting up a major incident reporting database. It describes how specific difficulties have been overcome and anticipates challenges for the future. CONCLUSIONS: We have successfully set up a major incident database, the main purpose of which is to have a repository of standardised major incident reports that can be analysed and compared in order to learn from them.

Can we identify patients at risk of life-threatening allergic reactions to food?

Anaphylaxis has been defined as a 'severe, life-threatening generalized or systemic hypersensitivity reaction'. However, data indicate that the vast majority of food-triggered anaphylactic reactions are not life-threatening. Nonetheless, severe life-threatening reactions do occur and are unpredictable. We discuss the concepts surrounding perceptions of severe, life-threatening allergic reactions to food by different stakeholders, with particular reference to the inclusion of clinical severity as a factor in allergy and allergen risk management. We review the evidence regarding factors that might be used to identify those at most risk of severe allergic reactions to food, and the consequences of misinformation in this regard. For example, a significant proportion of food-allergic children also have asthma, yet almost none will experience a fatal food-allergic reaction; asthma is not, in itself, a strong predictor for fatal anaphylaxis. The relationship between dose of allergen exposure and symptom severity is unclear. While dose appears to be a risk factor in at least a subgroup of patients, studies report that individuals with prior anaphylaxis do not have a lower eliciting dose than those reporting previous mild reactions. It is therefore important to consider severity and sensitivity as separate factors, as a highly sensitive individual will not necessarily experience severe symptoms during an allergic reaction. We identify the knowledge gaps that need to be addressed to improve our ability to better identify those most at risk of severe food-induced allergic reactions.

Intravenous iron administration and hypophosphatemia in clinical practice.

Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32-0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

Mental health nurses can increase capability and capacity in primary care by educating practice nurses: an evaluation of an education programme in England.

Most people with a mental health problem in England are cared for by clinicians in primary care who may have had little or no training in this area. Our aim was to develop an accessible education programme which was appropriate to the learning needs of this workforce. A survey of the mental health and well-being training needs and preferred learning methods of practice nurses was undertaken, then a programme of education was developed by a primary care mental health expert. Teaching was delivered by mental health nurses who were trained as educators. Both the practice nurses and mental health nurses felt their clinical practice would improve as a result of being involved in this programme. To sustain the learning, mental health nurses were supported by attending and then leading their own action learning sets. This model of education can be adapted and used by health organizations both nationally and internationally. Research is required to find out whether training practice nurses using this programme has an impact on patients.

The protein tyrosine phosphatase PRL-2 interacts with the magnesium transporter CNNM3 to promote oncogenesis.

The three PRL (phosphatases of regenerating liver) protein tyrosine phosphatases (PRL-1, -2 and -3) have been identified as key contributors to metastasis in several human cancers, yet the molecular basis of their pro-oncogenic property is unclear. Among the subfamily of PRL phosphatases, overexpression of PRL-2 in breast cancer cells has been shown to promote tumor growth by a mechanism that remains to be uncovered. Here we show that PRL-2 regulates intracellular magnesium levels by forming a functional heterodimer with the magnesium transporter CNNM3. We further reveal that CNNM3 is not a phosphorylated substrate of PRL-2, and that the interaction occurs through a loop unique to the CBS pair domains of CNNM3 that exists only in organisms having PRL orthologs. Supporting the role of PRL-2 in cellular magnesium transport is the observation that PRL-2 knockdown results in a substantial decrease of cellular magnesium influx. Furthermore, in PRL-2 knockout mice, serum magnesium levels were significantly elevated as compared with control animals, indicating a pivotal role for PRL-2 in regulating cellular magnesium homeostasis. Although the expression levels of CNNM3 remained unchanged after magnesium depletion of various cancer cell lines, the interaction between endogenous PRL-2 and CNNM3 was markedly increased. Importantly, xenograft tumor assays with CNNM3 and a mutant form that does not associate with PRL-2 confirm that CNNM3 is itself pro-oncogenic, and that the PRL-2/CNNM3 association is important for conferring transforming activities. This finding is further confirmed from data in human breast cancer tissues showing that CNNM3 levels correlate positively with both PRL-2 expression and the tumor proliferative index. In summary, we demonstrate that oncogenic PRL-2 controls tumor growth by modulating intracellular magnesium levels through binding with the CNNM3 magnesium transporter.

[Incomplete form of hypertrophc osteoarthropathy in a patient with breast cancer]. / LE CAS CLINIQUE DU MOIS. Ostéoarthropathie hypertrophique de forme incomplète chez une patiente présentant un cancer du sein.

Hypertrophic osteoarthropathy is sometimes the paraneoplasic manifestation of cancer of pulmonary origin. It is rarely present in case of breast cancer, even at a metastatic stage. In its complete form, this entity includes periostitis (predominantly bilateral and affecting upper and lower limbs), digital clubbing and, rarely, arthritis. We report the case of a female patient with metastatic breast cancer and an incomplete form of hypertrophic osteoarthropathy, clearly asymetric and without digital clubbing.

Non-invasive diagnosis of intracranial aneurysms.

Patients need to be examined for intracranial aneurysms if they have had a subarachnoid hemorrhage. The preferred technique in this situation is CT angiography. Screening can be done for familial forms or for elastic tissue disorders, for which the first line investigation is magnetic resonance angiography. These non-invasive methods have now taken over from conventional angiography that was reserved for the pretreatment phase. A good technical knowledge of these imaging methods, their artifacts and misleading images enables reliable detection of intracranial aneurysms and for an accurate report to be returned to clinicians.

Neurokinin-3 receptor activation in the retrochiasmatic area is essential for the full pre-ovulatory luteinising hormone surge in ewes.

Neurokinin B (NKB) is essential for human reproduction and has been shown to stimulate luteinising hormone (LH) secretion in several species, including sheep. Ewes express the neurokinin-3 receptor (NK3R) in the retrochiasmatic area (RCh) and there is one report that placement of senktide, an NK3R agonist, therein stimulates LH secretion that resembles an LH surge in ewes. In the present study, we first confirmed that local administration of senktide to the RCh produced a surge-like increase in LH secretion, and then tested the effects of this agonist in two other areas implicated in the control of LH secretion and where NK3R is found in high abundance: the preoptic area (POA) and arcuate nucleus (ARC). Bilateral microimplants containing senktide induced a dramatic surge-like increase in LH when given in the POA similar to that seen with RCh treatment. By contrast, senktide treatment in the ARC resulted in a much smaller but significant increase in LH concentrations suggestive of an effect on tonic secretion. The possible role of POA and RCh NK3R activation in the LH surge was next tested by treating ewes with SB222200, an NK3R antagonist, in each area during an oestradiol-induced LH surge. SB222200 in the RCh, but not in the POA, reduced the LH surge amplitude by approximately 40% compared to controls, indicating that NK3R activation in the former region is essential for full expression of the pre-ovulatory LH surge. Based on these data, we propose that the actions of NKB in the RCh are an important component of the pre-ovulatory LH surge in ewes.

Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran Sasso National Laboratory.

The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) µs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.

What does practice development (PD) offer mental health-care contexts? A comparative case study of PD methods and outcomes.

Practice development (PD) in mental health nursing has been progressing over the last decade; however, the level and impact of PD activity in the field of mental health remains poorly understood outside localized project impact. More specific reporting and comparative analysis of PD outcomes will improve this situation. In response, this paper presents three case scenarios from work taking place in Australia and New Zealand, as working examples of how PD methodologies have been applied within mental health practice settings. Using a comparative framework that captures the contributing assumptions, practices, processes and conditions imperative to effective PD work within a mental health-care context, three case vignettes are reviewed. The critical question driving this paper is 'what mental health-care services does PD offer in terms of transformational change approaches and the promotion of effective workplace cultures?' Conditions considered necessary for successful PD initiatives within mental health contexts are explored such as how PD converges and diverges with mental health-related theories, plus where and how PD activity best integrates with the specific elements associated with mental health-care provision. The findings are further reviewed in line with reports of PD outcomes from other fields of health care.

Pilot of BRAF mutation analysis in indeterminate, suspicious and malignant thyroid FNA cytology.

BACKGROUND: BRAF V600E mutation has been reported to show a high specificity for papillary thyroid carcinoma (PTC). Using this marker to upgrade 'indeterminate' or 'suspicious' thyroid fine needle aspiration (FNA) cytology to 'malignant' could potentially allow one-stage therapeutic total thyroidectomy. METHODS: For a 14-month period, FNA cytology specimens in the Thy3-5 categories, which are the UK equivalents of indeterminate (Thy3a, atypical; Thy3f, follicular), suspicious for malignancy (Thy4) and malignant (Thy5) in the Bethesda System, underwent BRAF mutation testing by melt curve analysis. The results were correlated with histology. RESULTS: We tested 123 cytology specimens of which 12 (9.8%) failed. The BRAF mutation rate in the remainder was 16.2% (18/111), with 93 showing the wild-type. Seventeen mutations were V600E and one was non-V600E. The rate of mutation increased significantly (P < 0.0001 if Thy3a and Thy3f were combined) with the cytology category: 1/42 Thy3a (2.4%), 1/36 Thy3f (2.8%), 4/15 Thy4 (26.7%), 12/18 Thy5 (66.7%). All BRAF mutations correlated with PTC on histology, except for one recurrent PTC without histology. One mutation-positive case with Thy3a cytology showed the target lesion to be a 10-mm follicular adenoma on histology with an immediately adjacent 4-mm micro-PTC, in a patient who did not require total thyroidectomy. CONCLUSION: BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.

From principles to practice: a spatial approach to systematic conservation planning in the deep sea.

Increases in the demand and price for industrial metals, combined with advances in technological capabilities have now made deep-sea mining more feasible and economically viable. In order to balance economic interests with the conservation of abyssal plain ecosystems, it is becoming increasingly important to develop a systematic approach to spatial management and zoning of the deep sea. Here, we describe an expert-driven systematic conservation planning process applied to inform science-based recommendations to the International Seabed Authority for a system of deep-sea marine protected areas (MPAs) to safeguard biodiversity and ecosystem function in an abyssal Pacific region targeted for nodule mining (e.g. the Clarion-Clipperton fracture zone, CCZ). Our use of geospatial analysis and expert opinion in forming the recommendations allowed us to stratify the proposed network by biophysical gradients, maximize the number of biologically unique seamounts within each subregion, and minimize socioeconomic impacts. The resulting proposal for an MPA network (nine replicate 400 × 400 km MPAs) covers 24% (1 440 000 km(2)) of the total CCZ planning region and serves as example of swift and pre-emptive conservation planning across an unprecedented area in the deep sea. As pressure from resource extraction increases in the future, the scientific guiding principles outlined in this research can serve as a basis for collaborative international approaches to ocean management.