The neutralising and stimulatory effects of antimicrobial peptide LL-37 in human gingival fibroblasts.

OBJECTIVES: To investigate the effects of LL-37, a broad spectrum antimicrobial peptide expressed in periodontal tissues, on human gingival fibroblast responsiveness to microbial challenge and to explore the direct effects of LL-37 on human gingival fibroblasts. DESIGN: The effect of LL-37 on bacterial lipopolysaccharide-induced expression of Interleukin (IL-6) and chemokine C-X-C motif ligand (CXCL) 8 was determined by enzyme linked immunosorbent assay (ELISA). LL-37's influence on bacterial lipopolysaccharide-induced IκBα degradation was investigated by western blot. DNA microarray analysis initially determined the direct effects of LL-37 on gene expression, these findings were subsequently confirmed by quantitative polymerase chain reaction and ELISA analysis of selected genes. RESULTS: Bacterial lipopolysaccharide-induced IL-6 and CXCL8 production by human gingival fibroblasts was significantly reduced in the presence of LL-37 at concentrations in the range of 1-10 µg/ml. LL-37 led to a reduction in lipopolysaccharide-induced IκBα degradation by Escherichia coli lipopolysaccharide and Porphyromonas gingivalis lipopolysaccharide (10 µg/ml). LL-37 (50 µg/ml) significantly altered the gene expression of 367 genes in human gingival fibroblasts by at least 2-fold. CXCL1, CXCL2, CXCL3, Interleukin-24 (IL-24), CXCL8, Chemokine (C-C motif) Ligand 2, and Suppressor of Cytokine Signalling 3 mRNA were significantly upregulated by LL-37. LL-37 also significantly stimulated expression of CXCL8, hepatocyte growth factor and CXCL1 at the protein level. CONCLUSION: LL-37 plays an important regulatory role in the immunomodulatory activity of gingival fibroblasts by inhibiting lipopolysaccharide -induced expression of inflammatory cytokines and directly stimulating the expression of an array of bioactive molecules involved in inflammation and repair.

International recruitment of radiographers and the development of a workplace integration support package: Project evaluation.

INTRODUCTION: In October 2020, a regional workforce action group was established jointly by Health Education England (HEE) and NHS England and Improvement (NHSEI) in the South West to work collaboratively to address the workforce challenges within diagnostic imaging. Fifty-eight internationally recruited radiographers were offered employment in departments across the region, the majority of them taking up their posts in the UK in early 2021. The aim of the study presented here was to evaluate the efficacy of a training resource developed by Plymouth Marjon University, with input from HEE and NHSEI, to support workplace and cultural integration for the new recruits. METHODS: The training package to help newly recruited radiographers from outside the UK integrate into their host departments was developed using flexible learning opportunities centred on reusable digital learning assets. Self-paced e-learning sessions were augmented by group 'connected' sessions online. Two surveys were undertaken, exploring the impact of this workforce integration programme for International radiographers joining the NHS. RESULTS: Survey results indicate that the integration programme's three-phase strategy has seen an impact on 6 out of 12 self-efficacy measures, raised awareness of challenges, and increased personal awareness of implications for practice. By the end of the programme, delegates were in the top two quintiles for their average well-being score. CONCLUSION: Principal recommendations include ensuring digital accessibility for new recruits as part of the on-boarding process, considering the timing of delivery of any online connected support sessions, the provision of long-term pastoral support; and mandating the training requirement for managers and team leaders. IMPLICATIONS FOR PRACTICE: Success of international recruitment campaigns can be enhanced through the implementation of an online integration package.

Social referents for dairy farmers: who dairy farmers consult when making management decisions.

Social referents provide information that aid in farmer decision making. Some social referents, such as veterinarians, have been well studied in the context of dairy farms, but others have not and the role of social referents may change across management practices. This study aimed to understand (1) who farmers consult when making management decisions across different animal care practices and (2) what characteristics of these social referents influence farmer decision making. Secondary thematic analysis was used on two qualitative datasets with dairy farmers from the lower Fraser Valley region of British Columbia, Canada. The two datasets included non-naturalistic data (i.e. interviews, participatory discussion groups) investigating two dairy farm management practices (calf care and transition period management). Analysis revealed four themes: (1) who farmers consult when making management decisions across practices and the role of these social referents, (2) personal and professional characteristics, and the diversity of opinions of social referents, (3) actions of social referents, and (4) the strength of the relationship between the social referent and farmer. Similarities were found across practices regarding the personal and professional characteristics of social referents, even though the role of these referents varied across contexts. Farmers valued diverse opinions and actions that social referents could provide, such as the provision of resources, recommendations, and interpretation of farm data. We recommend future research focused on strengthening the relationship between farmers and social referents.

Radiographer advanced and consultant practice and community diagnostic hubs - a vision for the future.

OBJECTIVES: This article combines a brief narrative review of the Richards Report with an overview of current radiographer advanced and consultant clinical practice (ACCP) to provide suggestions for future ACCP within radiography. KEY FINDINGS: The 'Diagnostics: Recovery and Renewal' report by Professor Sir Mike Richards, published in 2020, has identified a need for improvements to be made to diagnostic services. His recommendations include the introduction of Community Diagnostic Hubs (CDHs) that would provide quicker and easier access to diagnostic tests for patients(1) A narrative review around the concept of Advanced and Consultant Clinical Practice (ACCP) for radiographers demonstrates the capability of the radiographers to expand their role. The article concludes with a vision of how CDHs could potentially provide multiple career pathways for radiographers working at this level of practice. CONCLUSION AND IMPLICATIONS FOR PRACTICE: It is acknowledged that some of these concepts are a combination of visionary and aspirational in outlook rather than being entirely based on current practice. The intention of this article, and the implications for practice, are to support on-going discussions to enable radiography, as a profession, to seek ways and opportunities to do things differently whilst ensuring that the patient remains at the centre of the services delivered.

Demystifying the spontaneous phenomena of motor hyperexcitability.

Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes.

Using Realistic Evaluation to understand how interventions work on dairy farms.

Interventions that aim to help farmers change on-farm practices recommend that advisors communicate effectively with farmers, work collaboratively to set goals and provide farmers with resources that are applicable to the farm context. We developed an intervention that aimed to help farmers modify and use a standard operating procedure (SOP) for colostrum management; failure of passive transfer of immunoglobulins is common on dairy farms and SOPs for colostrum management are increasingly required by farm animal welfare assurance programs. We used Realistic Evaluation to evaluate whether, how and why our intervention to help farmers modify and use SOPs for colostrum management facilitated change and provide recommendations based on our approach that can improve the design and implementation of future interventions. We used a multiple case study on five farms over 8 months, collecting data through interviews, participant observation, document analysis and field notes. We identified three mechanisms that influenced whether participants modified and used their SOP. The purpose mechanism distinguished between participants who thought the aim of the SOP was for farm staff to learn and understand how to complete a task versus those who thought that the SOP was only useful for compliance with assurance programs. The utility mechanism distinguished between participants who thought that the SOP would be helpful for daily use on their farm, versus those who did not. The physical text mechanism distinguished between participants who used the templates we provided to modify and use their SOP, versus those who did not. A key contextual factor on all farms was participant belief of having capable and engaged staff on their farm; modification and use of the SOP did not occur unless this was the case. To facilitate change, intervention developers should actively participate in the intervention to develop an understanding of farmer needs, understand the purpose behind different goals set by farmers and integrate tools, advice and resource demonstrations when possible. We conclude that Realistic Evaluation is a useful framework for evaluating how contexts and mechanisms generate outcomes on farms, and to understand how, and in which contexts, complex interventions facilitate change. We suggest that this approach can improve the success of interventions and help direct the approaches used on different farms.

A Phase 2a Randomized, Double-Blind, Dose-Optimizing Study to Evaluate the Immunogenicity and Safety of a Bivalent DNA Vaccine for Hemorrhagic Fever with Renal Syndrome Delivered by Intramuscular Electroporation.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic hantaviruses found in Asia and Europe, respectively. DNA vaccines targeting the envelope glycoproteins of these viruses have been constructed and found to elicit neutralizing antibodies when delivered to humans by various technologies including intramuscular electroporation. Here, we report findings from a Phase 2a clinical trial of a combined HTNV/PUUV DNA vaccine delivered at varying doses and administration schedules using the Ichor Medical Systems TriGrid intramuscular electroporation delivery technology. The study was designed to characterize the effects of DNA vaccine dose and number of administrations on the frequency and magnitude of immunological response. Subjects (n = 120) were divided into four cohorts. Cohorts 1 and 2 received a dose of 2 mg of DNA (1 mg per plasmid), and cohorts 3 and 4 received a dose of 1 mg of DNA (0.5 mg per plasmid) each vaccination. Each of the four cohorts received a series of four administrations (days 0, 28, 56 and 168). For cohorts 1 and 3, the DNA vaccine candidate was delivered at each of the four administrations. For cohorts 2 and 4, in order to maintain blinding, subjects received the DNA vaccine on days 0, 56 and 168, but on day 28 received only the phosphate buffered saline vehicle rather the DNA vaccine. Sera were collected on days 0, 28, 56, 84, 140, 168, 196, 252 and 365 and evaluated for the presence of neutralizing antibodies by PUUV and HTNV pseudovirion neutralization assays (PsVNAs). Day 84 was also evaluated by a plaque reduction neutralization test (PRNT). Overall the PsVNA50 geometric mean titers (GMTs) and seropositivity rates among cohorts were similar. Cohort 3 exhibited the highest frequency of subjects that became seropositive to both PUUV and HTNV after vaccination, the highest peak GMT against both viruses, and the highest median titers against both viruses.

Between-teacher variance of students' teacher-rated risk for emotional, behavioral, and adaptive functioning.

As schools increasingly adopt universal social, emotional, and behavioral screening, more research is needed to examine the effects of between-teacher differences due to error and bias on students' teacher-rated screening scores. The current study examined predictors of between-teacher differences in students' teacher-rated risk across one global and three narrow domains of behavioral functioning. Participants included 2450 students (52.1% male, 54.2% White) and 160 teachers (92.1% female, 80.3% White) from four elementary schools in one Southeastern U.S. school district. Teachers rated student behavior on the Behavior Assessment System for Children (Third Edition) Behavioral and Emotional Screening System (BESS)-Teacher Form and completed a survey about their training and perspectives of common behavior problems. Results of multilevel linear regression found between-teacher effects to be greater for internalizing risk scores (intraclass correlation = 0.23) than for externalizing risk scores (intraclass correlation = 0.12) or adaptive behavior scores (intraclass correlation = 0.14). Statistically significant student predictors in most models included student grade, gender, race and/or ethnicity, office discipline referrals, and course grades. We also detected effects of several teacher-level variables in one or more of the models, including teacher gender, teacher ratings of problem severity and concern for hypothetical children displaying behavior problems, and the covariance of random teacher intercept and teacher random slopes for students' office discipline referrals. Although these factors explained some teacher-level variance in students' risk scores, a notable amount of variance between teachers remains unexplained. Future research is needed to fully understand, reduce, and account for differences between teacher ratings due to error and bias.

Is the Patient Activation Measure a valid measure of osteoarthritis self-management attitudes and capabilities? Results of a Rasch analysis.

BACKGROUND: The Patient Activation Measure (PAM-13) was developed using Rasch analysis to assess knowledge, skills and confidence in the management of one's health. Previous studies report positive relationships between PAM-13 scores, self-management behaviours and longitudinal health outcomes in adults with chronic disease. There is little extant measurement property evidence for the use of PAM-13 in specific osteoarthritis (OA) populations. This study tested measurement properties of the PAM-13 in people living with hip and knee OA. METHODS: Item response frequency analysis was conducted. Rasch analysis evaluated the fit of the PAM-13 data to the Rasch model. Model-data fit was evaluated using infit and outfit statistics; person/item reliability and person separation indices were computed. Unidimensionality was evaluated using Principal Components Analysis of Rasch residuals and the data were assessed for item redundancy. Differential Item Functioning (DIF) examined bias in respondent subgroups and correlations tested relationships between PAM-13 and other patient-reported outcomes. RESULTS: Two-hundred-and-seventeen PAM-13 surveys were completed; there were no missing responses, floor or ceiling effects. Person and item reliability were acceptable (0.98 and 0.87 respectively) with good separation (person separation index 2.58). Unidimensionality was evaluated, with 49.4% of the variance explained by the first eigenvector. There was evidence of potential local response-dependence. The Rasch fit statistics were acceptable (except for item-2). There were some issues identified with targeting of the PAM-13 items to people with higher ability and the item difficulty order was different to that proposed in original cohorts. Significant DIF was identified for sex and educational level for a small number of items. PAM-13 scores were moderately correlated with depressive symptoms on the Depression Anxiety Stress Scale and Assessment of Quality of Life-6D. There were small correlations between PAM-13 and Knee injury and Osteoarthritis Outcome Score pain and activities of daily living scores. CONCLUSIONS: This study provides some evidence of adequate person and item reliability, unidimensionality, and construct validity to support the use of PAM-13 to measure patient activation in people living with hip and knee OA. Possible limitations regarding targeting, different item difficulty order, DIF and local response dependence should be investigated in future research.

Rapid fabrication of collagen bundles mimicking tumor-associated collagen architectures.

Stromal collagen is upregulated surrounding a solid tumor and presents as dense, thick, linearized, and aligned bundles. The collagen bundles are continually remodeled during tumor progression, and their orientation with respect to the tumor boundary has been correlated with invasive state. Currently, reconstituted-collagen gels are the standard in vitro tumor cell-extracellular matrix interaction model. The reticular, dense, and isotropic nanofiber (~900 nm-diameter, on average) gels do not, however, recapitulate the in vivo structural features of collagen bundling and alignment. Here, we present a rapid and simple method to fabricate bundles of collagen type I, whose average thickness may be varied between about 4 µm and 9 µm dependent upon diluent temperature and ionic strength. The durability and versatility of the collagen bundles was demonstrated with their incorporation into two in vitro models where the thickness and alignment of the collagen bundles resembled various in vivo arrangements. First, collagen bundles aligned by a microfluidic device elicited cancer cell contact guidance and enhanced their directional migration. Second, the presence of the collagen bundles in a bio-inert agarose hydrogel was shown to provide a route for cancer cell outgrowth. The unique structural features of the collagen bundles advance the physiological relevance of in vitro collagen-based tumor models for accurately capturing tumor cell-extracellular matrix interactions. STATEMENT OF SIGNIFICANCE: Collagen in the tumor microenvironment is upregulated and remodeled into dense, thick, and aligned bundles that are associated with invasive state. Current collagen-based in vitro models are based on reticular, isotropic nanofiber gels that do not fully recapitulate in vivo tumor stromal collagen. We present a simple and robust method of rapidly fabricating cell-scale collagen bundles that better mimic the remodeled collagen surrounding a tumor. Interacting with the bundles, cancer cells exhibited drastically different phenotypic behaviors, compared to nanofiber scaffolds. This work reveals the importance of microscale architecture of in vitro tumor models. The collagen bundles provide physiologically relevant collagen morphologies that may be easily incorporated into existing models of tumor cell-extracellular matrix interactions.

A consensus-based framework for conducting and reporting osteoarthritis phenotype research.

BACKGROUND: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. METHODS: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. RESULTS: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. CONCLUSIONS: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.

The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS. METHODS: We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients. RESULTS: A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials. CONCLUSION: Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians. SIGNIFICANCE: Surface EMG techniques can enrich effective biomarker development in ALS.

Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis.

OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline. METHODS: Six ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection. RESULTS: Assessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2-13.1 minutes), processing times (10.7-49.5 seconds) and fasciculation frequencies (27.4-71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6-79.4 IQR). CONCLUSION: We hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings. SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

Preserving US microbe collections sparks future discoveries.

Collections of micro-organisms are a crucial element of life science research infrastructure but are vulnerable to loss and damage caused by natural or man-made disasters, the untimely death or retirement of personnel, or the loss of research funding. Preservation of biological collections has risen in priority due to a new appreciation for discoveries linked to preserved specimens, emerging hurdles to international collecting and decreased funding for new collecting. While many historic collections have been lost, several have been preserved, some with dramatic rescue stories. Rescued microbes have been used for discoveries in areas of health, biotechnology and basic life science. Suggestions for long-term planning for microbial stocks are listed, as well as inducements for long-term preservation.

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab.

OBJECTIVE: To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). METHODS: This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). RESULTS: Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. CONCLUSION: Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab.

2019 Chitranjan S. Ranawat Award: Elective joint arthroplasty outcomes improve in malnourished patients with nutritional intervention: a prospective population analysis demonstrates a modifiable risk factor.

AIMS: To date, no study has demonstrated an improvement in postoperative outcomes following elective joint arthroplasty with a focus on nutritional intervention for patients with preoperative hypoalbuminaemia. In this prospective study, we evaluated differences in the hospital length of stay (LOS), rate of re-admission, and total patient charges for a malnourished patient study population who received a specific nutrition protocol before surgery. PATIENTS AND METHODS: An analytical report was extracted from the electronic medical record (EMR; Epic, Verona, Wisconsin) of a five-hospital network joint arthroplasty patient data set between 2014 and 2017. A total of 4733 patients underwent joint arthroplasty and had preoperative measurement of albumin levels: 2220 at four hospitals and 2513 at the study hospital. Albumin ≤ 3.4 g/l, designated as malnutrition, was found in 543 patients (11.5%). A nutritional intervention programme focusing on a high-protein, anti-inflammatory diet was initiated in January 2017 at one study hospital. Hospital LOS, re-admission rate, and 90-day charges were compared for differential change between patients in study and control hospitals for all elective hip and knee arthroplasty patients, and for malnourished patients over time as the nutrition intervention was implemented. RESULTS: Malnourished patients with nutritional intervention at the study hospital had shorter hospital LOS beginning in 2017 than malnourished patients at control hospitals during the same period (p = 0.04). Similarly, this cohort had significantly lower primary hospitalization charges, charges associated with hospital re-admissions, and 90-day total charges (p < 0.001). Inclusion of covariant potential confounders (age, anaemia, diabetes, and obesity) did not alter the conclusions of the primary statistical analysis. CONCLUSION: Joint arthroplasty outcomes were positively affected in study patients with low albumin when a high-protein, anti-inflammatory diet was encouraged. Elective surgery was neither cancelled nor delayed with a malnutrition designation. While the entire network population experienced improved postoperative outcomes, malnourished control patients did not experience this improvement. This study demonstrated that education on malnutrition can benefit patients. Cite this article: Bone Joint J 2019;101-B(7 Supple C):17-21.

SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis.

OBJECTIVES: Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool. METHODS: Six ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model's predictive ability. RESULTS: By applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/- 0.2 SEM), specificity of 91.6% (+/- 0.1 SEM) and classification accuracy of 87.9% (+/- 0.1 SEM). An amplitude exclusion threshold (100 µV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394). CONCLUSION: We have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE). SIGNIFICANCE: Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.

Current concepts in joint pain in knee osteoarthritis.

Joint pain attributable to osteoarthritis (OA) is complex and influenced by a myriad of factors beyond local joint pathology. Current practice continues to predominantly adopt a biomedical approach to OA despite emerging evidence of the importance of a more holistic approach. This paper will summarise evidence for the presence of multidimensional pain profiles in knee joint pain and the presence of subgroups characterized by systemic features such as psychological distress, high comorbidity load or sensitisation of the nervous system. These factors have the potential to influence patient outcomes making them relevant for clinicians and highlighting the necessity of a broader multifactorial approach to assessment and treatment. This review describes the current state of the evidence for treatments of people with knee OA-related pain, including those receiving strong recommendations from current clinical guidelines, namely exercise, weight loss, self-management advice and pharmacological approaches. Other pain-modulating treatment options are emerging such as sleep and psychological interventions, pain education and multisensory retraining. The evidence and rationale for these newer therapeutic approaches is discussed. Finally, this review will highlight some of the limitations of current international guidelines for the management of OA and make recommendations for future research.

Psychiatric epidemiology and disaster exposure in Australia.

AIMS: To examine the lifetime prevalence and risk of psychiatric disorders associated with natural and man-made disaster exposure in Australia. METHODS: We utilised data from a nationally representative population survey (N = 8841) which were analysed through univariate and multivariate logistic regression in order to examine the full spectrum of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) affective, anxiety and substance use disorders associated with exposure to natural and man-made disaster. RESULTS: Man-made disaster exposure was primarily associated with an increased lifetime risk (odds ratio (95% CI)) of alcohol abuse disorder 2.29 (1.56-3.37), post-traumatic stress disorder (PTSD) 2.27 (1.36-3.79), obsessive-compulsive disorder (OCD) 1.95 (1.08-3.51) and major depressive disorder 1.69 (1.01-2.85). Multiple natural disaster exposure was associated with an increased lifetime risk of panic disorder 2.26 (1.11-4.61). Among the broader disorder spectrum examined, alcohol abuse disorder accounted for the single greatest increase in lifetime disorder prevalence associated with man-made disaster exposure, and the greatest number of natural or man-made disaster exposed individuals who had developed a lifetime psychiatric disorder. Despite the relatively greater disorder risk associated with man-made disaster, natural disaster exposure was associated with more cases of psychiatric disorder, likely due to the frequency with which these events occur in Australia. CONCLUSIONS: Notwithstanding the inability to draw causal inferences from cross-sectional survey data, population-based analyses provide a comprehensive and consistent method to ascertain the population imprint of psychiatric disorder and disaster exposure. Mental health policy and services should be targeting a range of psychiatric disorders in disaster contexts in addition to the usual focus on PTSD and depression, including alcohol abuse, panic disorder and OCD. Despite the relatively greater disorder risk associated with man-made disaster exposure, the national burden of psychiatric disorder in natural disaster contexts is particularly high.