Preliminary Laboratory Vibration Testing of a Complete Neonatal Patient Transport System.

Premature infants or neonates in need of advanced clinical care must be transported to specialized hospitals. Past studies have examined vibrations experienced by patients during transport; however, multiple confounding factors limit the utility of on-road data. Hence, the development of a standardized test environment is warranted. The overall purpose of this project is to characterize vibrations during neonatal patient transport and develop mitigation strategies to reduce exposure. This paper focusses on the development of a laboratory test environment and procedure that enables studying the equipment vibration in a comprehensive and repeatable manner. For the first time, a complete neonatal patient transport system, including a stretcher, has been mounted on an industrial shaker. Results largely validate the system's ability to simulate on-road vibrations with high repeatability.

Whole-body vibration in neonatal transport: a review of current knowledge and future research challenges.

Interfacility transport to tertiary care for high-risk neonates has become an integral part of equitable access to optimal perinatal healthcare. Excellence in clinical care requires expertise in transport medicine and the coordination of safe transport processes. However, concerns remain regarding environmental stressors involved in the transportation of sick high-risk neonates, including noise and vibration. In order to mitigate the potential deleterious effects of these physical stressors during transport, further knowledge of the burden of exposure, injury mechanisms and engineering interventions/modifications as adjuncts during transport would be beneficial. We reviewed the current literature with a focus on the contribution of new and emerging technologies in the transport environment with particular reference to whole-body vibration. This review intends to highlight what is known about vibration as a physical stressor in neonates and areas for further research; with the goal to making recommendations for minimizing these stressors during transport.

miPIE: NGS-based Prediction of miRNA Using Integrated Evidence.

Methods for the de novo identification of microRNA (miRNA) have been developed using a range of sequence-based features. With the increasing availability of next generation sequencing (NGS) transcriptome data, there is a need for miRNA identification that integrates both NGS transcript expression-based patterns as well as advanced genomic sequence-based methods. While miRDeep2 does examine the predicted secondary structure of putative miRNA sequences, it does not leverage many of the sequence-based features used in state-of-the-art de novo methods. Meanwhile, other NGS-based methods, such as miRanalyzer, place an emphasis on sequence-based features without leveraging advanced expression-based features reflecting miRNA biosynthesis. This represents an opportunity to combine the strengths of NGS-based analysis with recent advances in de novo sequence-based miRNA prediction. We here develop a method, microRNA Prediction using Integrated Evidence (miPIE), which integrates both expression-based and sequence-based features to achieve significantly improved miRNA prediction performance. Feature selection identifies the 20 most discriminative features, 3 of which reflect strictly expression-based information. Evaluation using precision-recall curves, for six NGS data sets representing six diverse species, demonstrates substantial improvements in prediction performance compared to three methods: miRDeep2, miRanalyzer, and mirnovo. The individual contributions of expression-based and sequence-based features are also examined and we demonstrate that their combination is more effective than either alone.

Assessment of bulbar function in amyotrophic lateral sclerosis: validation of a self-report scale (Center for Neurologic Study Bulbar Function Scale).

BACKGROUND AND PURPOSE: Impaired bulbar functions of speech and swallowing are among the most serious consequences of amyotrophic lateral sclerosis (ALS). Despite this, clinical trials in ALS have rarely emphasized bulbar function as an endpoint. The rater-administered Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) or various quality-of-life measures are commonly used to measure symptomatic benefit. Accordingly, we sought to evaluate the utility of measures specific to bulbar function in ALS. METHODS: We assessed bulbar functions in 120 patients with ALS, with clinicians first making direct observations of the degree of speech, swallowing and salivation impairment in these subjects. Clinical diagnosis of bulbar impairment was then compared with ALSFRS-R scores, speech rate, time to swallow liquids and solids, and scores obtained when patients completed visual analog scales (VASs) and the newly-developed 21-question self-administered Center for Neurologic Study Bulbar Function Scale (CNS-BFS). RESULTS: The CNS-BFS, ALSFRS-R, VAS and timed speech and swallowing were all concordant with clinician diagnosis. The self-report CNS-BFS and ALSFRS-R bulbar subscale best predicted clinician diagnosis with misclassification rates of 8% and 14% at the optimal cut-offs, respectively. In addition, the CNS-BFS speech and swallowing subscales outperformed both the bulbar component of the ALSFRS-R and speech and swallowing VASs when correlations were made between these scales and objective measures of timed reading and swallowing. CONCLUSIONS: Based on these findings and its relative ease of administration, we conclude that the CNS-BFS is a useful metric for assessing bulbar function in patients with ALS.

The role of candidate-gene CNTNAP2 in childhood apraxia of speech and specific language impairment.

Childhood apraxia of speech (CAS) is a debilitating pediatric speech disorder characterized by varying symptom profiles, comorbid deficits, and limited response to intervention. Specific Language Impairment (SLI) is an inherited pediatric language disorder characterized by delayed and/or disordered oral language skills including impaired semantics, syntax, and discourse. To date, the genes associated with CAS and SLI are not fully characterized. In the current study, we evaluated behavioral and genetic profiles of seven children with CAS and eight children with SLI, while ensuring all children were free of comorbid impairments. Deletions within CNTNAP2 were found in two children with CAS but not in any of the children with SLI. These children exhibited average to high performance on language and word reading assessments in spite of poor articulation scores. These findings suggest that genetic variation within CNTNAP2 may be related to speech production deficits.

Biliary boulders.

OBJECTIVE: To examine the outcome of endoscopic retrograde cholangiopancreatography (ERCP) in the management of common bile duct (CBD) stones. DESIGN: A retrospective review of 100 consecutive ERCPs performed for CBD stones. RESULTS: 100 ERCPs were performed on 84 patients with a median cohort age of 77. Completion in this cohort, as defined by duct clearance, was achieved in 65% of cases. Completion rates fell rapidly after two ERCPs. 33% of the cohort had small stones <10 mm, and 67% had stones >10 mm. Size, but not number of stones, affected the completion rate and frequency of complications (16%). Presence of periampullary diverticulum did not affect completion or complication rates. MR cholangiopancreatography (MRCP) had a 90% sensitivity for detecting CBD stones compared with 56% for CT. DISCUSSION AND CONCLUSIONS: ERCP remains a high-risk procedure with a significant complication rate when performed to deal with CBD stones. MRCP should be the second choice of investigation for CBD stones. This cohort had an unusually high number of larger stones at ERCP of 67% compared with other published UK cohorts of 8%, and this was reflected in the completion and complication rate.

The use of Complementary and Alternative Medicine in pregnancy: data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

OBJECTIVES: To report the frequency of Complementary and Alternative Medicine (CAM) use by a population of pregnant women in the UK. DESIGN: Four postal self-completion questionnaires completed at 8, 12, 18 and 32 weeks' gestation provided the source of CAMs used. Questions asked for written descriptions about the use of any treatments, pills, medicines, ointments, homeopathic medicines, herbal medicines, supplements, drinks and herbal teas. SETTING: An observational, population-based, cohort study of parents and children of 14,541 pregnant women residing within the former county of Avon in south-west England. Data was available for 14,115 women. RESULTS: Over a quarter (26.7%; n=3774) of women had used a CAM at least once in pregnancy, the use rising from 6% in the 1st trimester to 12.4% in the 2nd to 26.3% in the 3rd. Herbal teas were the most commonly reported CAM at any time in pregnancy (17.7%; n=2499) followed by homeopathic medicine (14.4%; n=2038) and then herbal medicine (5.8%; n=813). The most commonly used herbal product was chamomile used by 14.6% of women, the most commonly used homeopathic product was Arnica used by 3.1% of women. Other CAMs (osteopathy, aromatherapy, acupuncture/acupressure, Chinese herbal medicine, chiropractic, cranial sacral therapy, hypnosis, non-specific massage and reflexology) accounted for less than 1% of users. CONCLUSIONS: CAM use in pregnancy, where a wide range of CAMs has been assessed, has not been widely reported. Studies that have been conducted report varying results to this study (26.7%) by between 13.3% and 87% of pregnant women. Survey results will be affected by a number of factors namely the inclusion/exclusion of vitamins and minerals, the timing of data collection, the country of source, the number of women surveyed, and the different selection criteria of either recruiting women to the study or of categorising and identifying a CAM treatment or product.

CleanEMG--power line interference estimation in sEMG using an adaptive least squares algorithm.

This paper presents an adaptive least squares algorithm for estimating the power line interference in surface electromyography (sEMG) signals. The algorithm estimates the power line interference, without the need for a reference input. Power line interference can be removed by subtracting the estimate from the original sEMG signal. The algorithm is evaluated with simulated sEMG based on its ability to accurately estimate power line interference at different frequencies and at various signal-to-noise ratios. Power line estimates produced by the algorithm are accurate for signal-to-noise ratios below 15 dB (SNR estimation error at 15 dB is 14.7995 dB + 1.6547 dB).

A health equity methodology for auditing oral health and NHS General Dental Services in Sheffield, England.

OBJECTIVES: To describe a method used in a health equity audit (HEA) of oral health and National Health Service (NHS) General Dental Services. METHODS: Need, demand and provision of NHS General Dental Services were estimated by electoral ward using readily available data. Need was estimated using five-year-old dmft data. Scheduled and unscheduled demand were differentiated; scheduled demand was estimated using NHS dental registration data and unscheduled demand using emergency clinic and NHS Direct call activity data. Provision was estimated using self-declared dentist NHS hours and NHS Units of Dental Activity practice allocations. All variables were correlated with socioeconomic deprivation in each electoral ward, estimated by rates of receipt of Income Support. SETTING: Sheffield, England. RESULTS: Estimated need in electoral wards varied and correlated positively with increasing socio-economic deprivation. Scheduled demand tended to be lower and unscheduled demand higher in more deprived wards. Estimates of NHS General Dental Service provision indicated marginally higher provision in more deprived wards, though the correlation was weak. A synthesis of the findings estimated where need was least well met by provision. CONCLUSION: A HEA of oral health and NHS General Dental Services can be undertaken using readily available data. However, data used to estimate need, demand or provision may have to change for future audits as the data routinely collected changes.

Global investigation of protein-protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences.

Protein-protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of approximately 99.95% and executes 16,000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29,589 high confidence interactions of approximately 2 x 10(7) possible pairs. Of these, 14,438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.

Regional volumetric change of the tongue during mastication in pigs.

Structure and movement of the tongue have been studied extensively, but little study has been carried on its 3D deformation and ensuing volumetric changes during various functions. The purpose of this study is to investigate the volumetric changes of a regional section of the tongue during feeding. Four 12-week-old Yucatan miniature pigs were used. During natural mastication and water drinking, the width, length, thickness and volumetric changes were measured using six implanted ultrasonic crystals, which circumscribed a wedge-shaped volume in the region of the tongue body. Jaw movements were videotaped and digitized. Signals from these two sources were synchronized to allow real-time analyses. Significant volumetric changes (P < 0.001) were found in chewing, ingestion and drinking, and these changes were stereotypical in relation to rhythmic jaw movements. Volumetric change during chewing was not only more regular, but significantly larger (45.6%, P < 0.001) than that during ingestion (31.4%). The volumetric changes were less regular in drinking and the changing range (30.4%) was close to that during ingestion. Real-time analysis indicated that the volume began increasing at late jaw closing and reached the peak at late power stroke. The increase in duration of volume only took up 33.4% of the total chewing cycle length; significantly shorter than that of volume decrease. Correlation analysis revealed that the change in posterior dorsal and ventral widths had the greatest positive association with volumetric change (r = 0.43) in direction. The covariance calculations further indicated that dimensional changes in length and thickness coupled negatively with volumetric changes in amplitude. These results revealed that regional volumetric change of the tongue occurs during feeding and chewing requires larger volumetric changes than do ingestion and drinking. Volumetric expansion occurs in the phase of power stroke during chewing and is coupled with increases in widths in the direction and with decreases of thickness and length in the amplitude. The results further suggested that the regional volumetric expansion may play the determinant role in functional load production on its surrounding tissues, and may also imply that neuromuscular control of the tongue is region-specific, a notion incompatible with traditional scheme of categorizing muscle function in the tongue.

Dietary determinants of post-menopausal bone loss at the lumbar spine: a possible beneficial effect of iron.

INTRODUCTION: Previous studies suggesting different effects of diet on post-menopausal bone loss may have given conflicting results because they sometimes failed to exclude confounding conditions or used imprecise methodology. DESIGN: To identify dietary determinants of bone loss from the lumbar spine after menopause in women not taking hormone replacement who developed no evidence of spondylotic or sclerotic degenerative disease, forty-three women were followed with repeated (mean = 12) measurements of bone mineral density (BMD) at L2-4 for 11-14 years. Eleven developed evidence suggestive of degenerative disease and were excluded. Diet was assessed at the beginning of the study and 2.5 years later using 3-day and 7-day periods of weighed intakes. Nutrients estimated were: carbohydrate, fat, protein, fibre, calcium, magnesium, iron, phosphorus, copper, zinc and six vitamins. We tested the ability of diet to predict post-menopausal bone loss using stepwise regression. RESULTS: Each woman's BMD change was described by a single coefficient after log transformation of the BMD data. The best model for BMD loss including dietary factors alone had two significant determinants: daily energy or protein (p=0.0003) intake was adverse, while dietary iron (p=0.002) was predictive of bone maintenance, an effect that persisted if iron was expressed as a ratio to energy intake. Adding body mass index to the model increased the goodness of fit (R (2)adj rose from 0.33 to 0.42) without affecting the statistical significance of the dietary determinants. CONCLUSIONS: Diet may influence bone loss after menopause, with dietary iron (or an associated factor) possibly having a protective effect on bone at the spine.

Time series analysis of jaw muscle contraction and tissue deformation during mastication in miniature pigs.

Masticatory muscle contraction causes both jaw movement and tissue deformation during function. Natural chewing data from 25 adult miniature pigs were studied by means of time series analysis. The data set included simultaneous recordings of electromyography (EMG) from bilateral masseter (MA), zygomaticomandibularis (ZM) and lateral pterygoid muscles, bone surface strains from the left squamosal bone (SQ), condylar neck (CD) and mandibular corpus (MD), and linear deformation of the capsule of the jaw joint measured bilaterally using differential variable reluctance transducers. Pairwise comparisons were examined by calculating the cross-correlation functions. Jaw-adductor muscle activity of MA and ZM was found to be highly cross-correlated with CD and SQ strains and weakly with MD strain. No muscle's activity was strongly linked to capsular deformation of the jaw joint, nor were bone strains and capsular deformation tightly linked. Homologous muscle pairs showed the greatest synchronization of signals, but the signals themselves were not significantly more correlated than those of non-homologous muscle pairs. These results suggested that bone strains and capsular deformation are driven by different mechanical regimes. Muscle contraction and ensuing reaction forces are probably responsible for bone strains, whereas capsular deformation is more likely a product of movement.

Patient-led variable dosing with balsalazide as long-term therapy for maintenance in ulcerative colitis: a 3-year prospective observational study.

BACKGROUND: The patient-centred approach is new to the management of ulcerative colitis. To date, it has only been shown to be successful in a short-term study. AIM: To assess the feasibility, safety and efficacy of patient-led dosing using balsalazide in the long-term treatment of ulcerative colitis. METHODS: This was a 3-year, two-cohort, multi-centre study: one cohort was in stable remission (52 patients) and the other was newly in remission (76 patients) from ulcerative colitis. Two 750-mg balsalazide capsules were given twice daily for maintenance, increased by 750-mg increments to a maximum of 6 g for up to 7 days depending on symptom severity. Clinical assessments were made every 12-14 weeks; laboratory assessments were made every 6 months. RESULTS: The average median daily dose of balsalazide was 3 g (range, 1.5-6 g). In the cohort with stable remission, 23 patients (44%) had relapsed by 3 years [median time to relapse, > 1095 days (36 months)]. In the cohort newly in remission, these values were 45 patients (59%) and 656 days (22 months), respectively. In the cohort with stable remission, the time since last relapse was significantly associated with relapse during the first year of treatment (P < 0.033). CONCLUSIONS: Long-term, patient-led, maintenance treatment with balsalazide is well tolerated with a good safety profile and is effective for patients with ulcerative colitis.

A biomechanical evaluation of the role of labrum on anterior/posterior translation of shoulders at different degrees of abduction.

The objective of the study was to investigate the effects of anterior and posterior labrums on the anterior/posterior translations of shoulders. Thirteen cadaver shoulders were arthroscopically evaluated and nine were selected based on the absence of any pathological findings. These shoulders were tested intact, vented and after sequential arthroscpoic incision of the anterior and posterior labrums. The anterior/posterior translations were measured in a specially designed apparatus. The loads vs. displacement curves were obtained. The loads vs. displacement curves of the shoulders before and after labrum incision did not show any appreciable differences. Moreover the measured loads at 6 mm displacement did not show any statistically significant differences due to labrum incision. It was concluded that both anterior and posterior labrum incisions of the shoulders did not show any appreciable differences in anterior/posterior laxity. An arthroscopic technique was successfully developed to isolate the effect of labrum on the shoulder laxity.

Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats.

Zoledronic acid (ZOL) is a highly potent heterocyclic bisphosphonate which has been shown to inhibit bone resorption in short-term experiments in young growing animals. In this investigation we have evaluated the effects of a 1-year administration to mature, ovariectomized (OVX) rats as a model for postmenopausal osteoporosis in order to elucidate (1) the temporal changes in urinary biochemical markers of bone turnover and femoral bone mineral density (BMD), (2) to measure changes of static and dynamic histomorphometric parameters and mechanical strength, and (3) to assess the preventive effects of chronic treatment with ZOL on these parameters. In urine, deoxypyridinoline increased after OVX and was significantly reduced by ZOL administration, indicative of a reduced bone collagen turnover. These changes were accompanied by alterations of tibial cancellous bone: trabecular bone volume and parameters of bone architecture were significantly augmented by ZOL and bone formation rates fell as a consequence of suppressed bone turnover, but were still measurable. No signs of "frozen bone" or osteomalacia could be detected. BMD of the whole femurs rose in sham-operated control animals (SHAM) during the entire experimental period, whereas in OVX animals, BMD plateaued after 32 weeks at a lower level. ZOL at a low dose (0.3 mg/kg/week s.c.) did not alter whole femur BMD, but at higher doses (1.5 and 7.5 mg/kg/week s.c.) BMD increased to the level of the SHAM group. A distinct pattern was noted for the distal quarter of the femur, a region rich in cancellous bone: BMD initially increased in all treatment groups except the OVX group, and at a later stage fell again at a comparable rate irrespective of treatment. Mechanical stability, as assessed by a 3-point bending test, was significantly increased by all doses of ZOL and exceeded OVX and sham-operated controls. The effects on mechanical properties were observed at a low dose which did not measurably increase femoral BMD after 1-year treatment. Multiregression analysis revealed a significant positive correlation between maximum load and BMD, and a significant negative correlation of maximum load with labeled perimeter, a marker of bone formation and turnover. No significant correlation was found with urinary deoxypyridinoline, a marker of bone resorption. The data show that mechanical testing detects improvements of functional bone quality following low dose bisphosphonate treatment which are not identified by standard DXA measurements of BMD.

A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis.

BACKGROUND: Sulfasalazine is well established in the treatment of active ulcerative colitis. Intolerance to sulfasalazine, however, is a common problem. Balsalazide has been designed to deliver 5-aminosalicylic acid to the colon without the poor tolerability of sulfasalazine. AIM: To compare the safety and efficacy of balsalazide, 6.75 g daily, with sulfasalazine, 3 g daily, in the treatment of active ulcerative colitis of all grades of severity. METHODS: Balsalazide and sulfasalazine were compared in a multicentre, double-blind, parallel group study over 12 weeks. Patients were stratified for disease severity and topical and/or oral steroids were co-administered where clinically necessary. RESULTS: Fifty-seven patients were randomized: 28 to receive balsalazide and 29 to receive sulfasalazine. Significantly fewer patients withdrew from the balsalazide group due to adverse events (2/28 vs. 9/29, P=0.041). These data confirm that balsalazide is better tolerated than sulfasalazine. In patients able to tolerate the treatment, similar improvements were recorded in clinical, sigmoidoscopic and histological assessments in both treatment groups. CONCLUSIONS: This study confirms the better tolerability of balsalazide compared to sulfasalazine, and supports the use of balsalazide in ulcerative colitis of all grades of severity.

Maintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsules.

BACKGROUND: It may be possible to achieve more effective management of Crohn's Disease by introducing a flexible dosage regimen sensitive to patients' needs. AIM: Comparison of the efficacy and tolerability of a fixed vs. flexible budesonide controlled ileal release treatment regimen for the prevention and management of relapse in Crohn's disease patients. Budesonide controlled ileal release is an oral formulation which delivers drug directly to disease sites in the ileum and ascending colon, by preventing more proximal release and absorption. METHODS: A randomized, double-blind comparison of a fixed dose of budesonide controlled ileal release (6 mg o.m.) and a flexible dose of budesonide controlled ileal release (3, 6 or 9 mg o.m.) for 12 months, in 143 patients in remission from ileal or ileo-caecal Crohn's Disease. RESULTS: Very low rates of clinical relapse in Crohn's disease were achieved with budesonide controlled ileal release 6 mg o.m. There was no significant difference between the treatment groups with respect to the survival estimate of percentage of treatment failures (flexible group 15%, fixed group 19%; P=0.61). The average consumed dose of budesonide was comparable in both groups (5.8 mg flexible, 6.0 mg fixed). Similar proportions of patients reported adverse events (flexible 100%, fixed 97%). There were 33 serious adverse events (flexible 19, fixed 14) and 13 withdrawals due to significant adverse events (flexible 9, fixed 4). CONCLUSION: Maintenance treatment with budesonide controlled ileal release 6 mg o.m. is well-tolerated and is associated with low rates of clinical relapse in stable Crohn's disease over 12 months. Flexible dosing remains an option for individual patients, but this study has shown no advantage over a standard fixed dosing regimen.

Tolerability of aminosalicylates in inflammatory bowel disease.

Since its synthesis in the 1930s and subsequent introduction, sulfasalazine has been an effective treatment for inflammatory bowel disease. However, up to one-third of patients are unable to take the drug because of severe intolerance. The finding in 1977 that the anticolitic effect of sulfasalazine lay in its 5-aminosalicylic [(5-ASA); mesalazine] moiety led to the development of new generations of 5-ASA agents. These new agents include a slow continuous release formulation, pH-dependent release formulations, formulations using alternative carrier molecules and rectally administered formulations. Newer 5-ASA formulations are more effective than placebo in maintaining remission of ulcerative colitis. They have also been used for the treatment of active Crohn's disease as well as maintenance treatment of ileocolonic Crohn's disease, although their role in isolated small bowel disease is controversial. In general terms, all of the newer 5-ASA preparations are much better tolerated than sulfasalazine. The use of standard dosages of mesalazine in pregnancy appears to be tolerated; however, continuing surveillance of pregnancy outcome is recommended. While there is evidence that mesalazine can cause nephrotoxic reactions, these reactions can occur with all 5-ASA-containing preparations, particularly in individuals with existing renal disease. Blood dyscrasias can also occur with all aminosalicylates.