Laminitis is a common debilitating disease in horses that involves painful disruption of the lamellar dermo-epidermal junction within the hoof. This condition is often refractory to conventional ...anti-inflammatory analgesia and results in unremitting pain, which in severe cases requires euthanasia. The mechanisms underlying pain in laminitis were investigated using quantification of behavioural pain indicators in conjunction with histological studies of peripheral nerves innervating the hoof. Laminitic horses displayed consistently altered or abnormal behaviours such as increased forelimb lifting and an increased proportion of time spent at the back of the box compared to normal horses. Electron micrographic analysis of the digital nerve of laminitic horses showed peripheral nerve morphology to be abnormal, as well as having reduced numbers of unmyelinated (43.2%) and myelinated fibers (34.6%) compared to normal horses. Sensory nerve cell bodies innervating the hoof, in cervical, C8 dorsal root ganglia (DRG), showed an upregulated expression of the neuronal injury marker, activating transcription factor-3 (ATF3) in both large NF-200-immunopositive neurons and small neurons that were either peripherin- or IB4-positive. A significantly increased expression of neuropeptide Y (NPY) was also observed in myelinated afferent neurons. These changes are similar to those reported in other neuropathic pain states and were not observed in the C4 DRG of laminitic horses, which is not associated with innervation of the forelimb. This study provides novel evidence for a neuropathic component to the chronic pain state associated with equine laminitis, indicating that anti-neuropathic analgesic treatment may well have a role in the management of this condition.
To (i) describe the contraceptive practices of HIV care and treatment (HCTx) clients in Manzini, Swaziland, including their unmet needs for family planning (FP), and compare these with ...population-level estimates; and (ii) qualitatively explore the causal factors influencing contraceptive choice and use.
Mixed quantitative and qualitative methods were used. A cross-sectional survey conducted among HCTx clients (N=611) investigated FP and condom use patterns. Using descriptive statistics, findings were compared with population-level estimates derived from Swaziland Demographic and Health Survey data, weighted for clustering. In-depth interviews were conducted with HCTx providers (n=16) and clients (n=22) and analysed thematically.
64% of HCTx clients reported current contraceptive use; most relied on condoms alone, few practiced dual method use. Rates of condom use for FP among female HCTx clients (77%, 95% CI 71% to 82%) were higher than population-level estimates in the study region (50% HIV-positive, 95% CI 43% to 57%; 37% HIV-negative, 95% CI 31% to 43%); rates of unmet FP needs were similar when condom use consistency was accounted for (32% HCTx, 95% CI 26% to 37%; vs 35% HIV-positive, 95% CI 28% to 43%; 29% HIV-negative, 95% CI 24% to 35%). Qualitative analysis identified motivational factors influencing FP choice: fears of reinfection; a programmatic focus on condoms for people living with HIV; changing sexual behaviours before and after antiretroviral therapy (ART) initiation; failure to disclose to partners; and contraceptive side effect fears.
Fears of reinfection prevailed over consideration of pregnancy risk. Given current evidence on reinfection, HCTx services must move beyond a narrow focus on condom promotion, particularly for those in seroconcordant relationships, and consider diverse strategies to meet reproductive needs.
Today's business processes are more connected than ever before, driven by the ability to share the right information with the right partners at the right time. While this interconnectedness and ...situational awareness is crucial to success, it also opens the possibility for misuse of the same capabilities by sophisticated adversaries to spread attacks and exfiltrate or corrupt critical sensitive information. We have been investigating means to analyze behaviors of actors and assess trustworthiness of information to support real-time cyber security decision making through a concept called Behavior-Based Access Control (BBAC). The work described in this paper focuses on the statistical machine learning techniques used in BBAC to make predictions about the intent of actors establishing TCP connections and issuing HTTP requests. We discuss pragmatic challenges and solutions we encountered in implementing and evaluating BBAC, discussing (a) the general concepts underlying BBAC, (b) challenges we have encountered in identifying suitable datasets, (c) mitigation strategies to cope with shortcomings in available data, (d) the combination of clustering and support vector machines for performing classification at scale, and (e) results from a number of scientific experiments. We also include expert commentary from Air Force stakeholders and describe current plans for transitioning BBAC capabilities into the Department of Defense together with lessons learned for the machine learning community.
To quantitatively describe passive lower extremity range of motion in participants with spinal muscular atrophy (SMA) types 2 and 3, and to establish preliminary thresholds to identify individuals at ...risk for performing poorly on disease-specific motor function outcome measures.
Eighty participants with SMA types 2 and 3, enrolled in an international multicenter natural history study, were evaluated with lower extremity range of motion testing and the Hammersmith Functional Motor Scale-Expanded.
A hip extension joint angle of -7.5° or less for SMA type 2 and 0° or less for SMA type 3 identified diminished motor ability with good sensitivity. For knee extension, a joint angle of -9.0° or less for SMA type 2 or 0° or less for SMA type 3 was similarly sensitive.
Minimal hip and knee joint contractures were associated with diminished motor ability. Clinical trial designs should consider the effect of contractures on motor function.
•Strength, flexibility and function considerations for rehabilitation interventions for SMA.•Clinical outcome measures used to evaluate disease status and progression for SMA.•Assistive devices and ...technology resources for SMA.
ABSTRACT
Introduction: A recent Rasch analysis performed on the Hammersmith Functional Motor Scale—Expanded (HFMSE) in patients with spinal muscular atrophy (SMA) identified issues impacting scale ...validity, redundant items, and disordered thresholds on some items. Methods: We modified the HMFSE scoring based on the Rasch analysis and on expert consensus to establish whether the traditional scoring overestimated the number of patients with changes within 2 points from baseline. Data were collected retrospectively from multicenter data sets in 255 type 2 and 3 SMA patients. Results: The mean 12‐month changes using the new and the traditional scoring system did not differ significantly (P > 0.05). The numbers of patients who improved or decreased by >2 points were also similar. Conclusions: The presence of outliers using the traditional scoring system was not due to overestimation of changes in activities that were tested bilaterally or to discrepancies in the scoring hierarchy of individual items. Muscle Nerve 52:435–437, 2015
Uniquely, the asynchronous flight muscle myofibrils of many insects contain arthrin, a stable 1:1 conjugate between actin and ubiquitin. The function of arthrin is still unknown. Here we survey for ...the presence of arthrin in 63 species of insect across nine orders using Western blotting. Analysis of the evolutionary distribution shows that arthrin has evolved a limited number of times but at least once in the Diptera and once in the Hemiptera. However, the presence of arthrin does not correlate with any observed common features of flight mechanism, natural history, or morphology. We also identify the site of the isopeptide bond in arthrin from Drosophila melanogaster (Diptera) and Lethocerus griseus (Hemiptera) using mass spectrometry. In both species, the isopeptide bond is formed between lysine 118 of the actin and the C-terminal glycine 76 of ubiquitin. Thus, not only the ubiquitination of actin but also the site of the isopeptide bond has evolved convergently in Diptera and Hemiptera. In terms of the actin monomer, lysine 118 is near neither the binding sites of the major actin-binding proteins, myosin, tropomyosin, or the troponins, nor the actin polymerization sites. However, molecular modeling supports the idea that ubiquitin bound to an actin in one F-actin strand might be able to interact with tropomyosin bound to the actin monomers of the other strand and thereby interfere with thin filament regulation.
Background
Reablement is an intensive, time-limited intervention for people at risk of needing social care or an increased intensity of care. Differing from home care, it seeks to restore functioning ...and self-care skills. In England, it is a core element of intermediate care. The existing evidence base is limited.
Objectives
To describe reablement services in England and develop a service model typology; to conduct a mixed-methods comparative evaluation of service models investigating outcomes, factors that have an impact on outcomes, costs and cost-effectiveness, and user and practitioner experiences; and to investigate specialist reablement services/practices for people with dementia.
Methods
Work package (WP) 1, which took place in 2015, surveyed reablement services in England. Data were collected on organisational characteristics, service delivery and practice, and service costs and caseload. WP2 was an observational study of three reablement services, each representing a different service model. Data were collected on health (EuroQol-5 Dimensions, five-level version) and social care related (Adult Social Care Outcomes Toolkit – self-completed) quality of life, practitioner (Barthel Index of Activities of Daily Living) and self-reported (Nottingham Extended Activities of Daily Living scale) functioning, individual and service characteristics, and resource use. They were collected on entry into reablement (
n
= 186), at discharge (
n
= 128) and, for those reaching the point on the study timeline, at 6 months post discharge (
n
= 64). Interviews with staff and service users explored experiences of delivering or receiving reablement and its perceived impacts. In WP3, staff in eight reablement services were interviewed to investigate their experiences of reabling people with dementia.
Results
A total of 201 services in 139 local authorities took part in the survey. Services varied in their organisational base, their relationship with other intermediate care services, their use of outsourced providers, their skill mix and the scope of their reablement input. These characteristics influenced aspects of service delivery and practice. The average cost per case was £1728. Lower than expected sample sizes meant that a comparison of service models in WP2 was not possible. The findings are preliminary. At discharge (T1), significant improvements in mean score on outcome measures, except self-reported functioning, were observed. Further improvements were observed at 6 months post discharge (T2), but these were significant for self-reported functioning only. There was some evidence that individual (e.g. engagement, mental health) and service (e.g. service structure) characteristics were associated with outcomes and resource use at T1. Staff’s views on factors affecting outcomes typically aligned with, or offered possible explanations for, these associations. However, it was not possible to establish the significance of these findings in terms of practice or commissioning decisions. Service users expressed satisfaction with reablement and identified two core impacts: regained independence and, during reablement, companionship. Staff participating in WP3 believed that people with dementia can benefit from reablement, but objectives may differ and expectations for regained independence may be inappropriate. Furthermore, staff believed that flexibility in practice (e.g. duration of home visits) should be incorporated into delivery models and adequate provision made for specialist training of staff.
Conclusions
The study contributes to our understanding of reablement, and what the impacts are on outcomes and costs. Staff believe that reablement can be appropriate for people with dementia. Findings will be of interest to commissioners and service managers. Future research should further investigate the factors that have an impact on outcomes, and reabling people with dementia.
Funding
The National Institute for Health Research Health Services and Delivery Research programme.
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