Effectiveness of Abdominal Functional Electrical Stimulation for Improving Bowel Function in People With a Spinal Cord Injury: A Study Protocol for a Double-Blinded Randomized Placebo-Controlled Clinical Trial.

Background: People with a spinal cord injury (SCI) have a high rate of bowel-related morbidity, even compared with people with other neurological disorders. These complications lower quality of life and place a financial burden on the health system. A noninvasive intervention that improves the bowel function of people with an SCI should reduce morbidity, improve quality of life, and lead to cost savings for health care providers. Objectives: To investigate the effectiveness of noninvasive abdominal functional electrical stimulation (FES) for improving bowel function in people with a chronic SCI. Methods: A prospective, double-blinded, 1:1 randomized, placebo-controlled intervention trial will be conducted with 80 adults with chronic SCI (>12 months since injury) above T8 single neurological level. The intervention will be a 45-minute abdominal FES (or placebo) session, 3 days per week, for 6 weeks. Main Study Parameters/Endpoints: Primary endpoint is whole gut transit time before and after 6 weeks of abdominal FES. Secondary endpoints measured before and after 6 weeks of abdominal FES are (1) colonic transit time; (2) quality of life (EQ-5D-5L); (3) participant-reported bowel function (International SCI Bowel Function Basic Data Set Questionnaire and visual analogue scale); (4) respiratory function (forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow, maximal inspiratory pressure, and maximal expiratory pressure); (5) bladder symptoms (Neurogenic Bladder Symptom Score); (6) daily bowel management diary; and (7) unplanned hospital visits. Conclusion: Safety data will be collected, and a cost utility analysis using quality of life scores will be performed. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000386831.

Early markers of periodontal disease and altered oral microbiota are associated with glycemic control in children with type 1 diabetes.

OBJECTIVES: To determine the relationship between periodontal disease and glycemic control in children with type 1 diabetes and to characterize the diversity and composition of their oral microbiota. METHODS: Cross-sectional study including children with type 1 diabetes recruited from clinics at the Women's and Children's Hospital (Australia). Participants had a comprehensive dental assessment, periodontal examination, and buccal and gingival samples collected for 16S rRNA sequencing. RESULTS: Seventy-seven participants (age 13.3 ± 2.6 years, 38 males, BMI z-score 0.81 ± 0.75) had a diabetes duration of 5.6 ± 3.9 years and median HbA1c of 8.5% (range 5.8-13.3), 69.4 mmol/mol (range 39.9-121.9). Thirty-eight (49%) had early markers of periodontal disease. HbA1c was positively correlated with plaque index (Rho = 0.34, P = 0.002), gingival index (Rho = 0.30, P = 0.009), bleeding on probing (Rho = 0.44, P = 0.0001) and periodontal pocket depth >3 mm (Rho = 0.21, P = 0.06). A 1% increase in HbA1c was independently associated with an average increase in bleeding on probing of 25% (P = 0.002) and with an increase in the rate of sites with pocket depth >3 mm of 54% (P = 0.003). Higher HbA1c was independently related to increased phylogenetic alpha diversity (P = 0.008) and increased compositional variation (beta diversity P = 0.02) in gingival, but not buccal, microbiota. Brushing frequency, plaque index, and gingival index had a significant effect on microbiota composition, independent of HbA1c. CONCLUSIONS: Children with type 1 diabetes showed a continuous relationship between less favorable glycemic control and increased early markers of periodontal disease. Glycemic control was also related to the complexity and richness of the plaque microbiota, with diversity increasing as HbA1c levels increase.

Periodontal risk markers in children and adolescents with type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Periodontal disease is a frequent complication of diabetes in adults, and both conditions are associated with systemic inflammatory states. This systematic review and meta-analysis was conducted to establish the relative severity of periodontal disease risk markers in children and adolescents with type 1 diabetes (T1D). METHODS: A systematic search strategy using PubMed and EMBASE databases was performed to identify relevant studies assessing periodontal risk markers in children and adolescents and T1D through to February 2019. Eligible studies were assessed for quality and heterogeneity, and a random effects model was used to estimate differences in selected periodontal risk markers in children with T1D relative to healthy controls. RESULTS: The search identified 551 studies from which 23 were found to meet the inclusion criteria. Random effects meta-analyses demonstrated that relative to healthy controls, children and adolescents with T1D had higher mean values for plaque index, gingival index, bleeding on probing, pocket depth and clinical attachment loss (all P < .001). CONCLUSIONS: Risk markers for periodontal disease were found to be more pronounced among children and adolescents with T1D compared to healthy controls. Early referral of these at risk individuals for dental examination is recommended to allow for early intervention.

Circadian activity patterns of mammalian predators and prey in Costa Rica.

Temporal niche shifts can shape predator-prey interactions by enabling predator avoidance, enhancing feeding success, and reducing competition among predators. Using a community-based conservation approach, we investigated temporal niche partitioning of mammalian predators and prey across 12 long-term camera trap surveys in the Pacific slope and Talamanca Cordillera of Costa Rica. Temporal overlap and segregation were investigated between predator-prey and predator-predator pairs using overlap analysis, circular statistics, and relative abundance after accounting for differences in habitat, season, and human impact among sites. We made the assumption that predators select abundant prey and adjust their activity to maximize their temporal overlap, thus we predicted that abundant prey with high overlap would be preferred prey species for that predator. We also predicted that similar-sized pairs of predator species with the greatest potential for competitive interactions would have the highest temporal segregation. Our results supported the existence of temporal niche separation among the eight species of predators-the smaller Leopardus felids (ocelot, margay, oncilla) were primarily nocturnal, the largest felids (jaguar and puma) and coyote were cathemeral, and the smaller jaguarundi and tayra were mostly diurnal. Most prey species (67%) were primarily nocturnal versus diurnal or cathemeral (33%). Hierarchical clustering identified relationships among species with the most similar activity patterns. We discuss the primary prey and competitor species predicted for each of the eight predators. Contrary to our prediction, the activity pattern of similar-sized intraguild competitors overlapped more than dissimilar-sized competitors, suggesting that similar-sized predators are hunting the same prey at the same time. From this we conclude that prey availability is more important than competition in determining circadian activity patterns of Neotropical predators. Our results indicate the presence of a delicate balance of tropical food webs that may be disrupted by overhunting, leading to a depauperate community consisting of ubiquitous generalists and endangered specialists. With Central America a hotspot for hunting-induced "empty forests," community-based conservation approaches may offer the best road to reduce illegal hunting and maintain the biodiversity and community structure of tropical forest systems.

Los cambios temporales de nicho pueden amoldar las interacciones predador-presa al permitir a la presa evadir los predadores, mejorar la eficacia de la alimentación y reducir la competición entre predadores. Mediante muestreos con cámaras trampa en 12 sitios de la pendiente del Pacífico y la Cordillera de Talamanca de Costa Rica, investigamos la división temporal de los nichos de mamíferos predadores y presas usando un enfoque de conservación basado en la comunidad. Investigamos la superposición y segregación temporal entre pares predador-presa y predador-predador utilizando análisis de superposición, estadísticas circulares y abundancia relativa, teniendo en cuenta diferencias de hábitat, estacionales y de impacto humano entre los sitios. Asumimos que los predadores seleccionan presas abundantes y ajustan su actividad para maximizar su superposición temporal con éstas; por lo tanto, predijimos que una presa abundante con alta superposición sería una especie de presa preferida para ese predador. También predijimos que pares de especies de predadores de tamaño similar con el mayor potencial para interacciones competitivas tendrían la mayor segregación temporal. Nuestros resultados respaldaron la existencia de una separación temporal de nicho entre las ocho especies de predadores­determinamos que los felinos más pequeños del género Leopardus (manigordo, caucel, tigrillo) son principalmente nocturnos, los felinos más grandes (jaguar y puma) y el coyote son catemerales, y los jaguarundi y tayra más pequeños son principalmente diurnos. La mayoría de las especies de presas (67%) son principalmente nocturnas versus diurnas o catemerales (33%). Mediante análisis de agrupación jerárquica, identificamos relaciones entre especies con los patrones de actividad más similares. Para cada uno de los predadores discutimos las presas primarias predichas y las especies competidoras. Contrario a nuestra predicción, el patrón de actividad de los predadores intragremios de tamaño similar se superpone más que el de los competidores de distinto tamaño, lo que indica que los predadores de tamaño similar están cazando la misma presa y están activos al mismo tiempo. De esto concluimos que la disponibilidad de presas es más importante que la competición en cuanto a determinar los patrones de actividad circadiana de los predadores neotropicales. Nuestros resultados revelan que el delicado equilibrio de las redes tróficas tropicales puede ser interferido por la caza excesiva, lo que lleva a una comunidad depauperada compuesta por generalistas ubicuos y especialistas en peligro de extinción. Con América Central como un centro de "bosques vacíos" inducidos por la caza, los enfoques de conservación basados en la comunidad pueden ofrecer el mejor camino para reducir la caza ilegal, y mantener la biodiversidad y estructura ecológica comunitaria de los sistemas forestales tropicales.

Postgraduate Education in Pharmaceutical Medicine in Australia: Evaluation and Evolution to a Global Program Over 20 Years.

BACKGROUND: The Pharmaceutical Medicine program at the University of New South Wales provides postgraduate education for students seeking employment relating to development of new medicines and medical technology. The objective of this study was to determine which changes to the program were required to meet future educational needs of students. METHODS: Responses to questions from 76 students, tutors, lecturers, and stakeholders were obtained via Qualtrics surveys. RESULTS: Most respondents would recommend the program because of scope and program emphasis, content, quality of teaching, flexibility, and availability of distance and online content. Students valued links to industry and the national regulatory authority. Respondents recommended program content be current, expanded to meet needs of the Asia-Pacific region, and structured to ensure opportunities for networking and collaboration. CONCLUSIONS: Recommended changes to the program are being implemented to optimize skills and knowledge of graduates for roles in global pharmaceutical, medical technology, and biotechnology industries.

The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric Oncology Inpatient Population; a Prospective Study.

BACKGROUND: Oral mucositis can be a frequent and severe complication of chemotherapy in children. It can result in pain, infection, depression, prolonged admission, treatment delays, increase in patient morbidity, and increased costs. AIM: To record the prevalence and severity of oral mucositis among inpatients and explore the relationship of risks factors and the development of oral mucositis. DESIGN: During an 18-month period 643 clinical inpatient assessments were completed on 73 children who were admitted and had received chemotherapy in the last 14 days. RESULTS: There were 43 episodes of oral mucositis in 31 children; 42.5% of the inpatient population. World Health Organization assessment identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and 18.6% grade 4. Analysis revealed significant associations between patient diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis. Children had increased length of admission with increasing severity of oral mucositis (P=0.0005). CONCLUSIONS: The prevalence of oral mucositis was 42.5% among inpatients and admission length was increased with increasing severity. Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and neutropenic status were shown to influence the risk of developing oral mucositis.

The principles of tomorrow's university.

In the 21st Century, research is increasingly data- and computation-driven. Researchers, funders, and the larger community today emphasize the traits of openness and reproducibility. In March 2017, 13 mostly early-career research leaders who are building their careers around these traits came together with ten university leaders (presidents, vice presidents, and vice provosts), representatives from four funding agencies, and eleven organizers and other stakeholders in an NIH- and NSF-funded one-day, invitation-only workshop titled "Imagining Tomorrow's University." Workshop attendees were charged with launching a new dialog around open research - the current status, opportunities for advancement, and challenges that limit sharing. The workshop examined how the internet-enabled research world has changed, and how universities need to change to adapt commensurately, aiming to understand how universities can and should make themselves competitive and attract the best students, staff, and faculty in this new world. During the workshop, the participants re-imagined scholarship, education, and institutions for an open, networked era, to uncover new opportunities for universities to create value and serve society. They expressed the results of these deliberations as a set of 22 principles of tomorrow's university across six areas: credit and attribution, communities, outreach and engagement, education, preservation and reproducibility, and technologies. Activities that follow on from workshop results take one of three forms. First, since the workshop, a number of workshop authors have further developed and published their white papers to make their reflections and recommendations more concrete. These authors are also conducting efforts to implement these ideas, and to make changes in the university system.  Second, we plan to organise a follow-up workshop that focuses on how these principles could be implemented. Third, we believe that the outcomes of this workshop support and are connected with recent theoretical work on the position and future of open knowledge institutions.

Crops In Silico: Generating Virtual Crops Using an Integrative and Multi-scale Modeling Platform.

Multi-scale models can facilitate whole plant simulations by linking gene networks, protein synthesis, metabolic pathways, physiology, and growth. Whole plant models can be further integrated with ecosystem, weather, and climate models to predict how various interactions respond to environmental perturbations. These models have the potential to fill in missing mechanistic details and generate new hypotheses to prioritize directed engineering efforts. Outcomes will potentially accelerate improvement of crop yield, sustainability, and increase future food security. It is time for a paradigm shift in plant modeling, from largely isolated efforts to a connected community that takes advantage of advances in high performance computing and mechanistic understanding of plant processes. Tools for guiding future crop breeding and engineering, understanding the implications of discoveries at the molecular level for whole plant behavior, and improved prediction of plant and ecosystem responses to the environment are urgently needed. The purpose of this perspective is to introduce Crops in silico (cropsinsilico.org), an integrative and multi-scale modeling platform, as one solution that combines isolated modeling efforts toward the generation of virtual crops, which is open and accessible to the entire plant biology community. The major challenges involved both in the development and deployment of a shared, multi-scale modeling platform, which are summarized in this prospectus, were recently identified during the first Crops in silico Symposium and Workshop.

Implementation of a hospital oral care protocol and recording of oral mucositis in children receiving cancer treatment : a retrospective and a prospective study.

PURPOSE: This retrospective/prospective study was carried out to implement a standardized hospital oral care protocol and record the incidence of oral mucositis for inpatients with childhood cancer. METHODS: The implementation process included stages of collaboration, consultation, education, and evaluation. The retrospective part of the study documented the existing hospital oral care protocol and audited medical records of all pediatric patients diagnosed with cancer over a 12-month period. The frequency of recorded oral mucositis and the rate of referral to the pediatric dentistry department were assessed. Following evaluation of the retrospective study, the literature was searched to create a new hospital oral care protocol. Referral to the dental department was standardized and frequent in-service presentations were given to staff. The oral mucositis scale was recorded daily for all inpatients, and compliance rates were assessed. RESULTS: Fifty-nine patients' medical records were audited during the retrospective study. Oral mucositis prevalence was clearly documented at 34%, while an additional 20% lacked a definitive diagnosis. During the prospective study, 38 patients were followed and had a verified incidence of oral mucositis of 33%. The rate of compliance of implementing the oral mucositis scale improved from 41% during the first 4 months to 87% during last 3 months. Referral rates to the dental department increased from 53% during the retrospective study to 100% during the prospective study. CONCLUSIONS: Mutual understanding and collaboration between the oncology and dental departments in hospitals is crucial for standardizing patient care and for improving oral care standards.

Oral manifestations of cancer treatment in children: a review of the literature.

In Western countries, rising incidence and survival rates in childhood cancer have led to increased patient morbidity, including short- and long-term oral effects. Some acute oral complications occur three times more commonly in children than adults. This literature review sourced material from medical databases to discuss the acute and chronic oral complications of oncology treatment in children. The article explores caries, gingivitis, oral infections, and oral mucositis, as well as available tools for measuring their incidence, prevention, and treatment in children. Many tools and interventions appear to be available to prevent and treat oral complications of cancer treatment in children; however, they lack reliable and consistent research. Future research should use larger samples to report the incidence of oral complications, which would allow identification of children at increased risk. In addition, larger studies would provide baseline information to enable the construction of appropriate randomized clinical trials to test methods of prevention and proposed interventions for oral complications of cancer treatment in children.

Louisiana: a model for advancing regional e-Research through cyberinfrastructure.

Louisiana researchers and universities are leading a concentrated, collaborative effort to advance statewide e-Research through a new cyberinfrastructure: computing systems, data storage systems, advanced instruments and data repositories, visualization environments and people, all linked together by software programs and high-performance networks. This effort has led to a set of interlinked projects that have started making a significant difference in the state, and has created an environment that encourages increased collaboration, leading to new e-Research. This paper describes the overall effort, the new projects and environment and the results to date.

A naturalistic study of galantamine for Alzheimer's disease.

OBJECTIVE: To collect descriptive data on the treatment of Alzheimer's disease with galantamine under naturalistic conditions. STUDY DESIGN: This was a prospective, open-label, observational study. PATIENTS: Subjects (n = 345) with mild to moderately severe dementia of the Alzheimer's type were recruited from 48 hospitals in Australia. METHODS: Subjects were enrolled and received treatment with galantamine for 6 months in a clinical practice setting. Subjects were assessed at baseline and 3 and 6 months after starting treatment using the Mini-Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [the latter only if the baseline MMSE score was at least 25]. Subjects were also assessed using an abridged Instrumental Activities of Daily Living (IADL) questionnaire that included questions on using the telephone, ability to travel more than 1km outside the home, taking medications and managing money, and an 11-item behaviour assessment scale that measured aggression, sleep disturbance, disinhibition, personality changes, irritability, depression, agitation, apathy, inertia, hallucinations and aberrant motor behaviour. RESULTS: Of the 345 subjects who were enrolled in the study (intent-to-treat [ITT] population), 229 completed the baseline, 3- and 6-month visits (per-protocol [PP] population). The mean age of the PP population was 78.0 +/- 6.8 years. At 6 months, most PP subjects (70%) showed an increase in MMSE score compared with baseline, with a mean increase in score of 2.0 +/- 3.1 points from a baseline of 20.8 +/- 4.2 points. In the ITT population, 44% of subjects (151/345) showed an increase in MMSE after 6 months. If data were unavailable the patient was classified as a nonresponder. Of the 21 PP patients who were assessed using ADAS-cog, 18 (86%) demonstrated a decrease in the ADAS-cog score, reflecting an improvement in cognition. Of the ITT population, 33% (19/57) had a decreased ADAS-cog score after 6 months. Most PP subjects (86%) were considered responders according to the CIBIC-plus score, with 65% showing some improvement over 6 months of treatment. Of the ITT population, 54% (187/345) showed no deterioration in CIBIC-plus score after 6 months.No deterioration in IADL or behaviour assessments occurred in the majority of PP subjects over 6 months. CONCLUSIONS: In a clinical practice setting, the majority of subjects receiving galantamine who completed the study maintained their ratings of cognition, function, behaviour or global assessment over the 6-month period.

Prediction of voluntary activation, strength and endurance of elbow flexors in postpolio patients.

To examine the long-term effects of polio, maximal voluntary strength and voluntary activation of elbow flexor muscles of 177 patients from a postpolio clinic were investigated using twitch interpolation. Muscle endurance was studied in 142 patients during 45 min of submaximal exercise, and predictors of impaired muscle performance were investigated. Twenty-nine of 177 patients (16.4%) had impaired voluntary drive to their elbow flexor muscles, but only 16 (9.0%) had markedly reduced elbow flexor strength, despite 74 (41.8%) reporting they were initially affected in their tested limb and 172 (97.2%) patients reporting new generalized symptoms. Seven patients had impaired muscle endurance in the tests of strength and voluntary drive. During the submaximal exercise, 16 patients (11.3%) had impaired peripheral muscle endurance with normal voluntary activation. These results confirm a low incidence of impaired upper-limb muscle performance in postpolio patients, despite many patients having subjective symptoms consistent with postpolio syndrome. There was an increased relative risk for impaired muscle function in those patients with a subjective decrease in strength in the tested limb, a recent decline in activities of daily living in their tested limb, and who used orthotic devices in their tested limb. Monitoring of function in prior-polio patients with impaired muscle performance may be useful, particularly when combined with investigation of other potential contributory factors to the functional impairment.

Risk of falling: predictors based on reduced strength in persons previously affected by polio.

OBJECTIVES: To examine the contributions of sensorimotor factors to postural control and falling in people with prior polio and to determine whether these contributions differ from those found in normal populations. DESIGN: Survey and case-control study. SETTING: A falls and balance laboratory in Australia. PARTICIPANTS: Forty persons with prior polio (age range, 28-71 y) and 38 age- and sex-matched control subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lower-limb muscle strength, sway, vision, lower-limb sensation, reaction time, foot-tapping speed, and falls. RESULTS: Compared with the control subjects, the prior polio subjects performed similarly in sensory tests but worse in tests that involved a motor component. Within the prior polio group, lower-limb strength was strongly associated with postural sway on a compliant surface and explained more of the variance in sway than in control subjects. Prior polio subjects who fell multiple times had reduced lower-limb strength, slower reaction time, lower foot-tapping speed, and increased sway compared with those who fell less often. However, the rate of decline in lower-limb strength within the prior polio group did not exceed normal, age-related changes. CONCLUSIONS: This investigation of prior polio subjects provides an appropriate model for studying muscle weakness as a falls risk factor. Weakness was directly associated with falls, and had an indirect effect mediated through increased sway.