Dementia and osteoporosis in a geriatric population: Is there a common link?

AIM To determine the existence of a common pathological link between dementia and osteoporosis through reviewing the current evidence base. METHODS This paper reviews the current literature on osteoporosis and dementia in order to ascertain evidence of a common predisposing aetiology. A literature search of Ovid MEDLINE (1950 to June 2016) was conducted. The keywords “osteoporosis”, “osteoporotic fracture”, “dementia” and “Alzheimer’s disease” (AD) were used to determine the theoretical links with the most significant evidence base behind them. The key links were found to be vitamins D and K, calcium, thyroid disease, statins, alcohol and sex steroids. These subjects were then searched in combination with the previous terms and the resulting papers manually examined. Theoretical, in vitro and in vivo research were all used to inform this review which focuses on the most well developed theoretical common causes for dementia (predominantly Alzheimer’s type) and osteoporosis. RESULTS Dementia and osteoporosis are multifaceted disease processes with similar epidemiology and a marked increase in prevalence in elderly populations. The existence of a common link between the two has been suggested despite a lack of clear pathological overlap in our current understanding. Research to date has tended to be fragmented and relatively weak in nature with multiple confounding factors reflecting the difficulties of in vivo experimentation in the population of interest. Despite exploration of various possible mechanisms in search for a link between the two pathologies, this paper found that it is possible that these associations are coincidental due to the nature of the evidence available. One finding in this review is that prior investigation into common aetiologies has found raised amyloid beta peptide levels in osteoporotic bone tissue, with a hypothesis that amyloid beta disorders are systemic disorders resulting in differing tissue manifestations. However, our findings were that the most compelling evidence of a common yet independent aetiology lies in the APOE4 allele, which is a well-established risk for AD but also carries an independent association with fracture risk. The mechanism behind this is thought to be the reduced plasma vitamin K levels in individuals exhibiting the APOE4 allele which may be amplified by the nutritional deficiencies associated with dementia, which are known to include vitamins K and D. The vitamin theory postulates that malnutrition and reduced exposure to sunlight in patients with AD leads to vitamin deficiencies. CONCLUSION Robust evidence remains to be produced regarding potential links and regarding the exact aetiology of these diseases and remains relevant given the burden of dementia and osteoporosis in our ageing population. Future research into amyloid beta, APOE4 and vitamins K and D as the most promising aetiological links should be welcomed

The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer

BACKGROUND: A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour-stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas. METHODS: TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed. RESULTS: Tumours with ≥49% stroma were associated with better survival in female (OS P=0.008, HR=0.2-0.7; RFS P=0.006, HR=0.1-0.6) and male breast cancer (OS P=0.005, HR=0.05-0.6; RFS P=0.01, HR=0.87-5.6), confirmed in multivariate analysis. CONCLUSIONS: High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR

Online Dominating Set

This paper is devoted to the online dominating set problem and its variants. We believe the paper represents the first systematic study of the effect of two limitations of online algorithms: making irrevocable decisions while not knowing the future, and being incremental, i.e., having to maintain solutions to all prefixes of the input. This is quantified through competitive analyses of online algorithms against two optimal algorithms, both knowing the entire input, but only one having to be incremental. We also consider the competitive ratio of the weaker of the two optimal algorithms against the other. We consider important graph classes, distinguishing between connected and not necessarily connected graphs. For the classic graph classes of trees, bipartite, planar, and general graphs, we obtain tight results in almost all cases. We also derive upper and lower bounds for the class of bounded-degree graphs. From these analyses, we get detailed information regarding the significance of the necessary requirement that online algorithms be incremental. In some cases, having to be incremental fully accounts for the online algorithm's disadvantage.Comment: IMADA-preprint-c

SPAM detection: Naïve bayesian classification and RPN expression-based LGP approaches compared

An investigation is performed of a machine learning algorithm and the Bayesian classifier in the spam-filtering context. The paper shows the advantage of the use of Reverse Polish Notation (RPN) expressions with feature extraction compared to the traditional Naïve Bayesian classifier used for spam detection assuming the same features. The performance of the two is investigated using a public corpus and a recent private spam collection, concluding that the system based on RPN LGP (Linear Genetic Programming) gave better results compared to two popularly used open source Bayesian spam filters. © Springer International Publishing Switzerland 2016

Challenges and solutions to returning to clinical training after research: a multidisciplinary survey of integrated academic trainees in West Yorkshire, United Kingdom

Background Time out of clinical training can impact medical trainees’ skills, competence and confidence. Periods of Out of Programme for Research (OOPR) are often much longer than other approved mechanisms for time of out training. The aim of this survey study was to explore the challenges of returning to clinical training following OOPR, and determine potential solutions. Methods All current integrated academic training (IAT) doctors at the University of Leeds (United Kingdom) and previous IAT trainees undertaking OOPR in the local region (West Yorkshire, United Kingdom)(n = 53) were invited to complete a multidisciplinary survey. Results The survey was completed by 33 participants (62% response rate). The most relevant challenges identified were completing the thesis whilst transitioning back to clinical work, the rapid transition between full-time research and clinical practice, a diminished confidence in clinical abilities and isolation from colleagues. Potential solutions included dedicated funds allocated for the renewal of lapsed skills, adequate notice of the clinical rotation to which trainees return, informing clinical supervisors about the OOPR trainee returning to practice and a mandatory return to standard clinical days. Conclusions Addressing these issues has the potential to improve the trainee experience and encourage future trainees to take time out of training for research activities

Ventilatory muscle strength, diaphragm thickness and pulmonary function in world-class powerlifters.

Resistance training activates the ventilatory muscles providing a stimulus similar to ventilatory muscle training. We examined the effects of elite powerlifting training upon ventilatory muscle strength, pulmonary function and diaphragm thickness in world-class powerlifters (POWER) and a control group (CON) with no history of endurance or resistance training, matched for age, height and body mass

The role of ABCG2 in modulating responses to anti-cancer photodynamic therapy

The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transmembrane protein transporter is known for conferring resistance to treatment in cancers. Photodynamic therapy (PDT) is a promising anti-cancer method involving the use of light-activated photosensitisers to precisely induce oxidative stress and cell death in cancers. ABCG2 can efflux photosensitisers from out of cells, reducing the capacity of PDT and limiting the efficacy of treatment. Many studies have attempted to elucidate the relationship between the expression of ABCG2 in cancers, its effect on the cellular retention of photosensitisers and its impact on PDT. This review looks at the studies which investigate the effect of ABCG2 on a range of different photosensitisers in different pre-clinical models of cancer. This work also evaluates the approaches that are being investigated to address the role of ABCG2 in PDT with an outlook on potential clinical validation

Colour assessment outcomes – a new approach to grading the severity of color vision loss

INTRODUCTION: Recent studies have shown that a significant percentage of subjects with anomalous, congenital trichromacy can perform the suprathreshold, colour-related tasks encountered in many occupations with the same accuracy as normal trichromats. In the absence of detailed, occupation-specific studies, an alternative approach is to make use of new findings and the statistical outcomes of past practices that have been considered safe to produce graded, justifiable categories of colour vision that can be enforced. METHODS: We analyzed traditional color assessment outcomes and measured severity of colour vision loss using the CAD test in 1363 subjects (336 normals, 705 deutan, 319 protan and 3 tritan). The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. RESULTS: The correlation between the number of Ishihara (IH) test plates subjects fail and the severity of RG colour vision loss was very poor. The 38 plates IH test has high sensitivity when no errors are allowed (i.e., only 0.71% deutans and 0.63% protans pass). Protocols based on zero errors are uncommon since 18.15% of normal trichromats fail. The most common protocols employ either the 24 or the 14 plates editions with two or less errors. These protocols pass almost all normal trichromats, but the deutans and some protans that also pass (when two or less errors are allowed) can be severely deficient. This is simply because the most challenging plates have not been included in the 24 and 14 plates editions. As a result, normals no longer fail, but the deutans and protans that pass have more severe loss of colour vision since they fail less challenging plates. The severity of colour vision loss was measured in each subject and statistical, pass / fail outcomes established for each of the most commonly used, conventional colour assessment tests and protocols. DISCUSSION: Historical evidence and new findings that relate severity of loss to the effective use of colour signals in a number of tasks provide the basis for a new colour grading system based on six categories. A single colour assessment test is needed to establish the applicant’s Colour Vision category which can range from ‘supernormal’ (CV0), for the most stringent, colour-demanding tasks, to ‘severe colour deficiency’, when red / green colour vision is either absent or extremely weak (CV5)

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Trial of remote continuous versus intermittent NEWS monitoring after major surgery (TRaCINg): a feasibility randomised controlled trial

Background Despite medical advances, major surgery remains high risk with up to 44% of patients experiencing postoperative complications. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient’s mobility. The aim of this study was to evaluate the feasibility, acceptability and clinical outcomes of continuous remote monitoring after major surgery. Methods The study was a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery were randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring was achieved using the SensiumVitals® wireless patch which is worn on the patient’s chest and monitors heart rate, respiratory rate and temperature continuously, and alerts the nurse when there is deviation from pre-set physiological norms. Feasibility was assessed by evaluating recruitment rate, adherence to protocol and randomisation and the amount of missing data. Clinical outcomes included time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of hospital readmission within 30 days of discharge. Results One hundred and thirty-six patients were randomised between October 2018 and April 2019: 67 to the control group and 69 to the intervention group. Recruitment was completed prior to the 12 month target with a high rate of eligibility and consent. Missing data was limited only to questionnaire responses; no participants were lost to follow-up and only one participant was withdrawn due to loss of capacity. The number of patients classed as ‘drop-out’ due to design (8.1%) were less than anticipated, and there were no participants who crossed over into the alternative trial allocation group. Seventeen participants in the intervention group (28%) did not adhere to the monitoring protocol. No formal comparisons between arms was undertaken; however, participants had fewer unplanned critical care admissions (1 versus 5) and had a shorter average length of hospital stay (11.6 days (95% confidence interval 9.5–13.7 days) versus 16.2 days (95% confidence interval 11.3–21.2 days)) in the continuous vital signs monitoring group. The time taken to receive antibiotics in cases of sepsis was similar in both arms. A cost-utility analysis indicated that the remote monitoring system was cost-saving when compared to standard NEWS monitoring alone. Conclusions It is feasible to perform a large-scale randomised controlled trial of continuous remote monitoring after major surgery. Progression to a definitive multicentre randomised controlled trial would be appropriate, taking consideration of factors, such as patient adherence, that might mask the potential benefit of additional monitoring. Trial registration ISRCTN registry with study ID ISRCTN16601772. Registered 30 August 2017