Quotients of continuous convex functions on nonreflexive Banach spaces

On each nonreflexive Banach space X there exists a positive continuous convex function f such that 1/f is not a d.c. function (i.e., a difference of two continuous convex functions). This result together with known ones implies that X is reflexive if and only if each everywhere defined quotient of two continuous convex functions is a d.c. function. Our construction gives also a stronger version of Klee's result concerning renormings of nonreflexive spaces and non-norm-attaining functionals.Comment: 5 page

Machine Learning-Based Method for Personalized and Cost-Effective Detection of Alzheimer's Disease

Diagnosis of Alzheimer's disease (AD) is often difficult, especially early in the disease process at the stage of mild cognitive impairment (MCI). Yet, it is at this stage that treatment is most likely to be effective, so there would be great advantages in improving the diagnosis process. We describe and test a machine learning approach for personalized and cost-effective diagnosis of AD. It uses locally weighted learning to tailor a classifier model to each patient and computes the sequence of biomarkers most informative or cost-effective to diagnose patients. Using ADNI data, we classified AD versus controls and MCI patients who progressed to AD within a year, against those who did not. The approach performed similarly to considering all data at once, while significantly reducing the number (and cost) of the biomarkers needed to achieve a confident diagnosis for each patient. Thus, it may contribute to a personalized and effective detection of AD, and may prove useful in clinical settings.</p

Bioprofile Analysis:A New Approach for the Analysis of Biomedical Data in Alzheimer's Disease

This article presents a new approach for the analysis of biomedical data to support the management and care of patients with Alzheimer's disease (AD). The increase in prevalence of neurodegenerative disorders such as AD has led to a need for objective means to assist clinicians with the analysis and interpretation of complex biomedical data. To this end, we propose a "Bioprofile" analysis to reveal the pattern of disease in the subject's biodata. From the Bioprofile, personal "Bioindices" that indicate how closely a subject's data resemble the pattern of AD can be derived. We used an unsupervised technique (k-means) to cluster variables of the ADNI database so that subjects are divisible into those with the Bioprofile of AD and those without it. Results revealed that there is an "AD pattern" in the biodata of most AD and mild cognitive impairment (MCI) patients and some controls. This pattern agrees with a recent hypothetical model of AD evolution. We also assessed how the Bioindices changed with time and we found that the Bioprofile was associated with the risk of progressing from MCI to AD. Hence, the Bioprofile analysis is a promising methodology that may potentially provide a complementary new way of interpreting biomedical data. Furthermore, the concept of the Bioprofile could be extended to other neurodegenerative diseases.</p

A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

Anomalous high-magnetic field electronic state of the nematic superconductors FeSe₁₋ₓSₓ

Understanding superconductivity requires detailed knowledge of the normal electronic state from which it emerges. A nematic electronic state that breaks the rotational symmetry of the lattice can potentially promote unique scattering relevant for superconductivity. Here, we investigate the normal transport of superconducting FeSe1−xSx across a nematic phase transition using high-magnetic fields up to 69 T to establish the temperature and field dependencies. We find that the nematic state is dominated by a linear resistivity at low temperatures that evolves towards Fermi-liquid behavior, depending on the composition x and the impurity level. Near the nematic end point, we find an extended temperature regime with ∼T1.5 resistivity, different from the behavior found near an antiferromagnetic critical point. The variation of the resistivity exponent with temperature reflects the importance of the nematoelastic coupling that can also suppress divergent critical fluctuations at the nematic end point. The transverse magnetoresistance inside the nematic phase has a ∼H1.55 dependence over a large magnetic field range and it displays an unusual peak at low temperatures inside the nematic phase. Our study reveals anomalous transport inside the nematic phase, influenced by both changes in the electronic structure and the scattering with the lattice and spin fluctuations

Standing up in Multiple Sclerosis (SUMS): Protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

This study is funded by the NIHR Health Technology Assessment Programme (14/176/12), United Kingdom.Background:  Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed ‘Balance Right in MS’ (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls. Our eventual aim is to assess the clinical and cost effectiveness of BRiMS in people with secondary progressive MS by undertaking an appropriately statistically powered, multi-centre, assessor-blinded definitive, randomised controlled trial. This feasibility study will assess the acceptability of the intervention and test the achievability of running such a definitive trial. Methods/design:  This is a pragmatic multi-centre feasibility randomised controlled trial with blinded outcome assessment. Sixty ambulant people with secondary progressive MS who self-report two or more falls in the previous 6 months will be randomly allocated (1:1) to either the BRiMS programme plus usual care or to usual care alone. All participants will be assessed at baseline and followed up at 15 weeks and 27 weeks post-randomisation. The outcomes of this feasibility trial include: • Feasibility outcomes, including trial recruitment, retention and completion • Assessment of the proposed outcome measures for the anticipated definitive trial (including measures of walking, quality of life, falls, balance and activity level) • Measures of adherence to the BRiMS programme • Data to inform the economic evaluation in a future trial • Process evaluation (assessment of treatment fidelity and qualitative evaluation of participant and treating therapist experience) Discussion:  The BRiMS intervention aims to address a key concern for MS service users and providers. However, there are several uncertainties which need to be addressed prior to progressing to a full-scale trial, including acceptability of the BRiMS intervention and practicality of the trial procedures. This feasibility trial will provide important insights to resolve these uncertainties and will enable a protocol to be finalised for use in the definitive trial.Publisher PDFPeer reviewe

Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review

<p>Abstract</p> <p>Background</p> <p>Cannabis therapy has been considered an effective treatment for spasticity, although clinical reports of symptom reduction in multiple sclerosis (MS) describe mixed outcomes. Recently introduced therapies of combined Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) extracts have potential for symptom relief with the possibility of reducing intoxication and other side effects. Although several past reviews have suggested that cannabinoid therapy provides a therapeutic benefit for symptoms of MS, none have presented a methodical investigation of newer cannabinoid treatments in MS-related spasticity. The purpose of the present review was to systematically evaluate the effectiveness of combined THC and CBD extracts on MS-related spasticity in order to increase understanding of the treatment's potential effectiveness, safety and limitations.</p> <p>Methods</p> <p>We reviewed MEDLINE/PubMed, Ovid, and CENTRAL electronic databases for relevant studies using randomized controlled trials. Studies were included only if a combination of THC and CBD extracts was used, and if pre- and post-treatment assessments of spasticity were reported.</p> <p>Results</p> <p>Six studies were systematically reviewed for treatment dosage and duration, objective and subjective measures of spasticity, and reports of adverse events. Although there was variation in the outcome measures reported in these studies, a trend of reduced spasticity in treated patients was noted. Adverse events were reported in each study, however combined TCH and CBD extracts were generally considered to be well-tolerated.</p> <p>Conclusion</p> <p>We found evidence that combined THC and CBD extracts may provide therapeutic benefit for MS spasticity symptoms. Although some objective measures of spasticity noted improvement trends, there were no changes found to be significant in post-treatment assessments. However, subjective assessment of symptom relief did often show significant improvement post-treatment. Differences in assessment measures, reports of adverse events, and dosage levels are discussed.</p

A systematic review of biomarkers for disease progression in Parkinson's disease

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