Gait disorders are associated with non-cardiovascular falls in elderly people: a preliminary study

BACKGROUND: The association between unexplained falls and cardiovascular causes is increasingly recognized. Neurally mediated cardiovascular disorders and hypotensive syndromes are found in almost 20 percent of the patients with unexplained falls. However, the approach to these patients remains unclear. Gait assessment might be an interesting approach to these patients as clinical observations suggests that those with cardiovascular or hypotensive causes may not manifest obvious gait alterations. Our primary objective is to analyze the association between gait disorders and a non-cardiovascular cause of falls in patients with unexplained falls. A second objective is to test the sensitivity and specificity of a gait assessment approach for detecting non-cardiovascular causes when compared with intrinsic-extrinsic classification. METHODS: Cross-sectional study performed in a falls clinic at a university hospital in 41 ambulatory elderly participants with unexplained falls. Neurally mediated cardiovascular conditions, neurological diseases, gait and balance problems were assessed. Gait disorder was defined as a gait velocity < 0.8 m/s or Tinetti Gait Score <9. An attributable etiology of the fall was determined in each participant. Comparisons between the gait assessment approach and the attributable etiology regarding a neurally mediated cardiovascular cause were performed. Fisher exact test was used to test the association hypothesis. Sensitivity and specificity of gait assessment approach and intrinsic-extrinsic classification to detect a non-cardiovascular mediated fall was calculated with 95% confidence intervals (CI95%). RESULTS: A cardiovascular etiology (orthostatic and postprandial hypotension, vasovagal syndrome and carotid sinus hypersensitivity) was identified in 14% of participants (6/41). Of 35 patients with a gait disorder, 34 had a non-cardiovascular etiology of fall; whereas in 5 out of 6 patients without a gait disorder, a cardiovascular diagnosis was identified (p < 0.001). Sensitivity and specificity of the presence of gait disorder for identifying a non-cardiovascular mediated cause was 97.1% (CI95% = 85–99) and 83% (CI95% = 36–99), respectively. CONCLUSION: In community dwelling older persons with unexplained falls, gait disorders were associated with non-cardiovascular diagnosis of falls. Gait assessment was a useful approach for the detection of a non-cardiovascular mediated cause of falls, providing additional value to this assessment

Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study

Background Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. Aims To describe initiation of psychotropic medication in the first year after partner bereavement. Methods In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. Results The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. Conclusion Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use

The Challenge Non-Typhoidal Salmonella (CHANTS) Consortium: Development of a non-typhoidal Salmonella controlled human infection model: Report from a consultation group workshop, 05 July 2022, London, UK [version 2; peer review: 2 approved]

Invasive non-typhoidal Salmonella disease (iNTS) is a major cause of morbidity and mortality globally, particularly as a cause of bloodstream infection in children and immunocompromised adults in sub-Saharan Africa. Vaccines to prevent non-typhoidal Salmonella (NTS) would represent a valuable public health tool in this setting to avert cases and prevent expansion of antimicrobial resistance. Several NTS and combination typhoidal-NTS vaccine candidates are in early-stage development, although the pathway to licensure is unclear due to challenges in conducting large phase III field trials. Controlled human infection models (CHIM) present an opportunity to accelerate vaccine development for a range of enteric pathogens. Several recent typhoidal Salmonella CHIMs have been conducted safely and have played pivotal roles in progressing vaccine candidates to pre-qualification and licensure. The Challenge Non-Typhoidal Salmonella (CHANTS) consortium has been formed with funding from the Wellcome Trust, to deliver the first NTS CHIM, which can act as a platform for future vaccine evaluation. This paper reports the conclusions of a consultation group workshop convened with key stakeholders. The aims of this meeting were to: (1) define the rationale for an NTS CHIM (2) map the NTS vaccine pipeline (3) refine study design and (4) establish potential future use cases

leap ucd 2017 centrifuge tests at cambridge

As part of the LEAP project the seismic response of a liquefiable 5° slope was modelled at a number of centrifuges around the world. In this paper the two experiments conducted at Cambridge University are discussed. The model preparation is detailed with particular emphasis on the sand pouring, saturation and slope cutting process. The presence of the third harmonic in the input motion is shown and its significance discussed. The potential for wavelet denoising to filter random electrical noise from the pore pressure traces is illustrated. CPT strength profiles are highlighted and a possible softer layer in one of the tests is discussed. Whilst the specifications called for one dense and one loose test, the likelihood that both Cambridge tests were loosely poured is assessed. The PIV technique is used to obtain the displacements of the slope during the test. Finally, the correspondence between the PIV displacements and physical measurements of the marker movements is compared

Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development

Background MC1R, a G‐protein coupled receptor with high affinity for alpha‐melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk. MC1R mutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentation in utero alter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight. Methods and Results By in situ hybridization, RT‐PCR and immunohistochemistry, we show that MC1R is widely expressed during human, chick and mouse embryonic and fetal stages in many somatic tissues, particularly in the musculoskeletal and nervous systems, and conserved across evolution in these three amniotes. Its dynamic pattern differs from that of TUBB3, a gene overlapping the same locus in humans and encoding class III β‐tubulin. The αMSH peptide and the transcript for its precursor, pro‐opiomelanocortin (POMC), are similarly present in numerous extra‐cutaneous tissues. MC1R genotyping of variants p.(V60M) and p.(R151C) was undertaken for 867 healthy children from the Avon Longitudinal Study of Parent and Children (ALSPAC) cohort, and birthweight modeled using multiple logistic regression analysis. A significant positive association initially found between R151C and birth weight, independent of known birth weight modifiers, was not reproduced when combined with data from an independent genome‐wide association study of 6,459 additional members of the same cohort. Conclusions These data clearly show a new and hitherto unsuspected role for MC1R in noncutaneous solid tissues before birth

The Search for Invariance: Repeated Positive Testing Serves the Goals of Causal Learning

Positive testing is characteristic of exploratory behavior, yet it seems to be at odds with the aim of information seeking. After all, repeated demonstrations of one’s current hypothesis often produce the same evidence and fail to distinguish it from potential alternatives. Research on the development of scientific reasoning and adult rule learning have both documented and attempted to explain this behavior. The current chapter reviews this prior work and introduces a novel theoretical account—the Search for Invariance (SI) hypothesis—which suggests that producing multiple positive examples serves the goals of causal learning. This hypothesis draws on the interventionist framework of causal reasoning, which suggests that causal learners are concerned with the invariance of candidate hypotheses. In a probabilistic and interdependent causal world, our primary goal is to determine whether, and in what contexts, our causal hypotheses provide accurate foundations for inference and intervention—not to disconfirm their alternatives. By recognizing the central role of invariance in causal learning, the phenomenon of positive testing may be reinterpreted as a rational information-seeking strategy

Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. CONCLUSIONS: Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Using focus groups to design systems science models that promote oral health equity

Background While the US population overall has experienced improvements in oral health over the past 60 years, oral diseases remain among the most common chronic conditions across the life course. Further, lack of access to oral health care contributes to profound and enduring oral health inequities worldwide. Vulnerable and underserved populations who commonly lack access to oral health care include racial/ethnic minority older adults living in urban environments. The aim of this study was to use a systematic approach to explicate cause and effect relationships in creating a causal map, a type of concept map in which the links between nodes represent causality or influence. Methods To improve our mental models of the real world and devise strategies to promote oral health equity, methods including system dynamics, agent-based modeling, geographic information science, and social network simulation have been leveraged by the research team. The practice of systems science modeling is situated amidst an ongoing modeling process of observing the real world, formulating mental models of how it works, setting decision rules to guide behavior, and from these heuristics, making decisions that in turn affect the state of the real world. Qualitative data were obtained from focus groups conducted with community-dwelling older adults who self-identify as African American, Dominican, or Puerto Rican to elicit their lived experiences in accessing oral health care in their northern Manhattan neighborhoods. Results The findings of this study support the multi-dimensional and multi-level perspective of access to oral health care and affirm a theorized discrepancy in fit between available dental providers and patients. The lack of information about oral health at the community level may be compromising the use and quality of oral health care among racial/ethnic minority older adults. Conclusions Well-informed community members may fill critical roles in oral health promotion, as they are viewed as highly credible sources of information and recommendations for dental providers. The next phase of this research will involve incorporating the knowledge gained from this study into simulation models that will be used to explore alternative paths toward improving oral health and health care for racial/ethnic minority older adults