A multi-scale investigation of habitat selectivity in Coastal Plain stream fishes

Studying the habitat use of Coastal Plain fishes enables us to develop a deeper understanding of how fishes thrive in this highly variable environment. Based on previous research by Dr. Roberts and his students, Coastal Plain fishes seem to sort into two groups: (1) species selecting stream reaches that continue to flow throughout the summer (i.e., fluvial species [F]) and (2) species occurring in streams that may stop flowing in late summer (i.e., nonfluvial species [NF]). For this study, I took a detailed look at eight of these species, spanning the F-NF gradient, and asked which environmental variables (e.g., water quality, stream size, adjacent land use) most influence species occurrence at the spatial scales of stream reaches and microhabitats. Habitat availability and use data came from electrofishing and habitat surveys of 25 sites sampled in summer 2016 and 12 sites re-sampled in summer 2018. At the reach scale, Random forest models indicated that F species consistently selected sites with higher dissolved oxygen, pH, and conductivity, whereas NF species tended to show the opposite pattern. Neither group showed consistent selectivity for stream-size, physical-habitat, or land-use variables. At the microhabitat scale, F species specialized on coarser substrate and higher velocity but showed no preference for large woody debris (LWD). In contrast, NF species specialized on low-velocity and high-LWD microhabitat configurations but showed no substrate selectivity. These findings suggest that habitat selection of Coastal Plain fishes is scale-dependent, and potentially interacts with morphology, feeding strategy, and water-quality tolerance

Fulfilling Lives: Supporting people with multiple needs, Evaluation Report, Year 1

This report is prepared for the Big Lottery Fund (the Fund) by the national evaluationteam and provides emerging findings and lessons learned from the first year of thenational evaluation of the Fulfilling Lives: Supporting people with multiple needsinitiative hereafter referred to as Fulfilling Lives (multiple needs).The national evaluation has been designed to determine the degree to which the initiativeis successfully achieving its aims and how they are being achieved. The evaluation will beboth formative and summative in nature, in that, it will inform the ongoing design and delivery of Fulfilling Lives (multiple needs) and its component projects as well as assessoverall achievements and value for money to inform future decision and policy making.Within this context, the evaluation has a number of objectives:— To track and assess the achievements of the initiative and to estimate the extent to whichthese are attributable to the projects and interventions delivered.— To calculate the costs of the projects and the corresponding value of benefits to theexchequer and wider society. This will enable an assessment of value for money of theprogramme and for individual interventions.— To identify what interventions and approaches work well, for which people, families andcommunities and in which circumstances and contexts.— To assess the extent to which the Big Lottery Fund's principles are incorporated into projectdesign and delivery and to determine the degree to which these principles affect successfuldelivery and outcomes.— To explore project implementation, understand problems faced and to facilitate theidentification of solutions and lessons learned

Critical Appraisal Bibliography, Scientific Abstract, and Matrix/Evidence Table

Introduction and Background As chronic and acute pain disorders continue to be diagnosed in the clinical setting, the number of patients searching for medical care in hopes of alleviating their symptoms is on the rise. Working in both medical and psychiatric facilities as a certified nursing assistant, I saw opioids frequently prescribed as a pharmacological treatment for individuals looking to lessen the pain associated with a multitude of pain related disorders. Working in long term care facilities, I watched individuals who had never struggled with substance use disorders develop clinical dependencies on narcotic medication due to the fact that they were prescribed opioids as a means of pain reduction. I watched as individuals who had no prior history of substance abuse or addiction begin to scream in anger and frustration every four hours demanding their medication the second it was available to them after undergoing an event that caused them to experience severe pain (e.g, invasive procedures, falls, etc). Being even a few minutes late to administer their narcotic medication could mean completely destroying a therapeutic rapport with a patient. I saw patients who were previously able to carry out pleasant conversation spending all day in an opioid induced stupor, declining in neurological functioning, and so high from their medication, they were unable to complete ADLs without extensive assistance from a member of the healthcare team. While the patient is not to blame for this phenomenon, as they are just doing what is available to them as treatment for their condition, the healthcare system is doing patients a disservice by not offering alternative forms of pain management for individuals suffering with pain related symptoms. Because of this, we became interested in researching the opioid crisis, how it came to be, and ways that healthcare providers can help to reduce the amount of patients who are forced to deal with clinical dependency and opioid induced debilitation by providing alternative forms of pain management, specifically for individuals experiencing post-operative pain, as it was the most common trigger of pain I saw in the patient populations I have worked with in the clinical setting. Purpose Statement The population we will be researching includes individuals experiencing postoperative pain, who would typically undergo pharmacotherapy with opioids to alleviate their symptoms. The interventions we will be researching include ways that the registered nurse and providers can help reduce their patient’s pain using different forms of alternative pain management that do not include opioid medication. We will be comparing the effectiveness and practicality of opioid therapy to that of other forms of pain management to better understand the ways that patients can work to reduce their pain symptoms in ways that do not include narcotic medication. The way we will evaluate outcomes is by evaluating the current literature surrounding the topic and comparing the results from studies comparing the effectiveness of opioid therapy and the results from alternative forms of pain management. Literature Review In order to research this topic in greater depth, we used google scholar, PubMed, and CINAHL to ensure that each source we used was evidence-based and peer reviewed to the information we gathered was accurate, unbiased, and applicable to the clinical setting. Some databases we utilized included The National Library of Medicine, The Journal of Nursing Regulation, & Arthroscopy: The Journal of Arthroscopic & Related Surgery, all evidence-based and peer-reviewed databases. Luckily, there is an objectively large amount of data existing around the concept of pain management, as it is such a prevalent problem for individuals seeking medical care. Findings After researching forms of alternative pain management for post operative patients, we found three concepts to explore as an alternative to narcotic medication for pain management. These three concepts include: acupuncture therapy, low dose steroid use, and medical cannabis. There is strong evidence to support the effectiveness of these three treatments for managing pain symptoms. While the research on medical cannabis for post operative pain tends to be limited due to legality issues and issues regarding how to correctly dose the drug, there is large evidence to support the effectiveness of cannabis for chronic pain disorders and neuropathy that can result from undergoing surgical procedures. Conclusion After reviewing these three concepts as a form of alternative pain management, we found that there is evidence to support these forms of treatment as a viable alternative to opioid medication, or by implementing these treatments, patients may be able to reduce the amount of opioids it takes to alleviate their pain, reducing their chances of developing side effects or overdosing. There are gaps in the literature regarding cannabis as an effective treatment for acute pain due to complications of researching a schedule one substance, but there is evidence to support cannabis as a treatment for chronic pain issues that can develop from invasive surgical procedures. It is important that nurses are informed about these methods of alternative pain management in order to ensure that their clients are undergoing the best course of care possible if opioids are not a reasonable form of treatment for managing postoperative pain

The development and feasibility of an intervention to promote physical activity following pulmonary rehabilitation in people with Chronic Obstructive Pulmonary Disease

Background: Despite the importance of physical activity to physical and psychological health in chronic obstructive pulmonary disease (COPD), levels of physical activity in COPD patients are significantly lower than age matched healthy individuals. Pulmonary rehabilitation, a structured physical activity intervention, is one of the essential treatments for COPD, and results in benefits such as improved exercise capacity, symptoms, and quality of life. However, this does not translate to an increase in long term physical activity and previous interventions to promote physical activity following pulmonary rehabilitation have had limited efficacy. Aim: The overarching aim of this thesis was to develop and test the feasibility and acceptability of an intervention to promote physical activity following pulmonary rehabilitation in patients with COPD. Methods: This mixed methods thesis developed and tested the feasibility of an intervention in line with the stages outlined in the Medical Research Council framework. The intervention was informed by a qualitative systematic review and the development of the intervention was facilitated by the Behaviour Change Wheel and collaboration with stakeholders. The intervention was tested in a feasibility cluster randomised controlled trial with an embedded process evaluation. The primary outcome of the feasibility study was the acceptability of the intervention and secondary outcomes included other feasibility outcomes and a range of clinical measures proposed for a definitive trial. Acceptability of the intervention and the research procedures were also explored via semi-structured interviews with patients and focus groups with personnel involved in delivery of the intervention (health care professionals and WhatsApp leaders). An inductive analysis was conducted to analyse the data. The factors which impacted patients’ physical activity were also identified via a deductive analysis of the interviews with patients, and mapped to the capability, opportunity, motivation behaviour change model (COM-B). Results: A thematic synthesis of fourteen studies revealed that beliefs, social support, and the environment encapsulate the factors which are important in physical activity following pulmonary rehabilitation in patients with COPD. The Behaviour Change Wheel guided the development of an intervention that included the provision of a pedometer and step diary, and the addition of patients to a WhatsApp group populated by fellow pulmonary rehabilitation graduates and a ‘WhatsApp leader’ for 52 weeks following pulmonary rehabilitation. A total of 74 patients enrolled in the feasibility study (consent rate, 55%) and there was an attrition rate of 35% at 52 weeks. By 52 weeks, 49% had engaged in the step diary, and 58% of participants who had consented to use WhatsApp had sent at least one WhatsApp message to the group. The Control Group had a larger decline in their daily steps at 52 weeks compared to the Intervention Group, MD, -180, (-765, 1126). Participants in the intervention group who engaged in the step diary had a smaller decline in their daily steps at 52 weeks compared to those who did not engage in the step diary, MD, 45.5 (-1796, 1889). Participants in the intervention group who engaged in WhatsApp had a smaller decline in daily steps at 52 weeks compared to those who did not engage in WhatsApp, MD, 730 (-992, 2454). However, results also suggest there was a larger detrimental decline in secondary health outcomes in the Intervention Group compared to the Control Group. WhatsApp leaders adhered to sending a minimum of weekly physical activity messages throughout the 52 weeks period. Common themes from interviews and focus groups were that patients would benefit from more familiarity with the intervention components (e.g. earlier introduction of the intervention to patients during PR from health care professionals), and that the convenience of the intervention components and research procedures could be improved (e.g. options for participants to use their personal mobile and pedometer devices). Rapport between the patients and WhatsApp leaders was considered important and face to face support should complement social networking following Pulmonary Rehabilitation. Facilitators unique to those with higher intervention engagement related to physical capability and reflective motivation (e.g. reduction in exacerbations following Pulmonary Rehabilitation and the ability to overcome mental obstacles). Barriers unique to those with lower intervention engagement related to automatic motivation and physical opportunity (e.g. low mood and the distance of physical activity opportunities). Conclusion: This thesis addressed the gaps in previous literature and adopted a step wise approach in the development and feasibility testing of the intervention. The intervention was considered acceptable and feasible, yet modifications are required to optimise the acceptability and feasibility of the study prior to a definitive cluster randomised controlled trial, which are possible during an intervention revision period

Investigating the role of hydrogen sulfide in the myometrium

Preterm births are increasing worldwide; currently 7 % of UK births are preterm. Prematurity is the principal cause of neonatal mortality and a major cause of paediatric morbidity. Uterine contractility before term leads to pre-term labour. Therefore to reduce pre-term delivery, new pathways and drugs that inhibit uterine contractility are of interest. The gasotransmitter H2S has been shown to inhibit myometrial contractility without much mechanistic insight and thus is of potential interest. Hydrogen sulfide (H2S) is produced in vivo from L-cysteine, by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). At least two enzymes degrade H2S; thiosulfate sulphur transferase (TST) and ethylmalonic encephalopathy 1 (Ethe1). Thus H2S will be regulated within cells. NaHS, which releases a rapid bolus of H2S, reduces myometrial contractility. However it is not clear if an H2S-generating system is present throughout gestation or if more physiological modes of H2S production can affect contractility. Previous studies used NaHS as a H2S producer, which is toxic and releases H2S as a non-physiological bolus and thus alternative H2S donors suitable for drug development are sought. A new H2S generating compound, GYY4137, developed to slowly release H2S which better reflects physiological conditions, appears to be such a drug. The aims of this work were to: (1) characterise the non-pregnant human myometrial tissue to determine the inherent spontaneous activity, to monitor whether the contractions were stable enough to assess H2S effects when compared to the term human myometrium. In addition, to monitoring changes in contractility in response to age, menopausal state and whether the women have endometriosis, (2) examine throughout gestation, the effects of GYY4137 on rat myometrial contractility, (3) investigate the differences in response to GYY4137 in non- pregnant versus pregnant human myometrium (4) compare GYY4137 effects to those of NaHS and L-cysteine in rat and human tissues, (5) elucidate the mechanism of H2S effects, and (6) determine the myometrial expression of enzymes governing tissue H2S levels. Non-pregnant human myometrium gave rise to stable spontaneous contractions. The older women become the lower the amplitude and area under the curve of contractions. High K+ depolarisations were also diminished with advanced age. As women reach post menopause contractions are found to decline when compared to pre-menopausal women. Women with endometriosis showed decreased amplitude with increased frequency of contractions when compared to their fertile, healthy counterparts. This finding suggested a potential involvement of altered myometrial activity in women suffering this condition. NaHS, L-cysteine and GYY produce uterine relaxation in a dose-dependent manner using rat and human tissues. NaHS and GYY4137 effects increased throughout gestation using rat myometrial tissue, possibly due to changes in H2S removal rates. TST, a H2S breakdown enzyme was not detectable in different gestation rat as well as in non- pregnant and term pregnant human myometrial tissue, implying no involvement.. Labouring rat myometrium however was not affected by either H2S producer. These data suggest that H2S contributes to uterine quiescence until labour onset. Term human myometrial contractions, both spontaneous and oxytocin-stimulated produced similar inhibitory responses to H2S producers NaHS and GYY4137. Non-pregnant spontaneous human contractions were unaffected on application of H2S producers. GYY4137 and L-cysteine decreased Ca transients, suggesting it affects L-type Ca channels, perhaps via sulfhydration of residues. These data were further supported upon use of BayK 8644 a calcium channel opener showing reduced effects of L-cysteine. KATP channels were also shown to be involved in the mechanism of H2S in the myometrium as use of KATP channel blocker glibenclamide caused reduced effects of the H2S producer GYY4137. These data suggest that H2S is an attractive target for therapeutic manipulation of human myometrial contractility and drugs such as GYY4137 will be effective. Both CBS and CSE are present in all the tissues tested in this thesis. It was also demonstrated that these enzymes were down regulated at term perhaps showing a role in preparing the myometrium for the onset of labour as the enzymes have been shown to further decline in labouring tissues. In conclusion, the work I have undertaken in this thesis strengthens the evidence of a physiologically important role for H2S in the myometrium and suggests it targets ion channels to affect calcium signalling and thus contractions

What are the patient reported facilitators and barriers to physical activity following pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD)? A systematic review of qualitative research

Objectives/purpose: This study aimed to determine and understand COPD patients’ perceived facilitators and barriers to physical activity after completion of pulmonary rehabilitation. Pulmonary rehabilitation, a multidisciplinary treatment for COPD incorporating exercise trail. Design: A systematic review of qualitative research. Methods: Electronic databases of published, (MEDLINE, Embase, Web of Science, CINAHL, ASSIA, PsycINFO and SPORTDiscus), non-published data and conference proceedings (DART Europe E theses, EThOS, Open Grey, The New York Academy of Medicine, ProQuest Dissertations and theses), and trial registers (ClinicalTrials.gov and Current Controlled Trials) were searched to identify qualitative studies (interviews, focus groups) including COPD patients following pulmonary rehabilitation. Qualitative data relevant to the research question were synthesised using an inductive, thematic approach. Results: 14 studies (n= 12 published articles, n= 2 theses) including 167 COPD patients (male = 92, female = 75) met the inclusion criteria. Analytical themes were beliefs, motivation and social support, which encapsulated the facilitators and barriers to physical activity following pulmonary rehabilitation. Facilitators included positive intentions, support from health care professionals (HCPs), positive feedback regarding health, access and opportunities to attend physical activity maintenance groups, peer and family interaction. Barriers included negative beliefs, lack of 27 support from HCPs and peers, as well as practical issues surrounding travel and home responsibilities following pulmonary rehabilitation. Conclusions: Our findings reflect the complexity of physical activity behaviour and provide implications regarding the importance of continued social support and feedback in the maintenance of physical activity. These factors should be considered in the development of future interventions that target physical activity following pulmonary rehabilitation in patients with COPD

Donor milk intake and infant growth in a South African neonatal unit: a cohort study

Background Implications of donor milk feedings on infant growth in resource limited settings remain uncertain. This knowledge gap includes the impact of donor milk availability on infant intake of mother’s own milk. Therefore, this investigation aimed to measure intake and growth in infants receiving donor milk when born to women from resource limited backgrounds with high rates of human immunodeficiency virus (HIV). Methods A retrospective cohort study enrolled eligible infants admitted to a South African combined neonatal intensive and secondary high care unit, within a one year admission period during 2015, with signed consent for donor milk feedings. A certified milk bank provided donor milk. Daily nutritional intake during the first month was recorded. Details included proportional intake of donor milk, mother’s own milk and infant formula. The primary outcome of infant growth velocity from day back to birth weight to discharge was calculated when length of stay was ≥14 days. Analyses primarily used T-tests; mixed effects models compared weekly calorie intake. Results One hundred five infants with donor milk consent were born at 30.9 ± 3.6 weeks of gestation, weighing 1389 ± 708 g. Forty percent of mothers had HIV. Infant growth velocity did not differ based on percent of feedings as donor milk (≥ 50%: 11.8 ± 4.9 g/kg/d; < 50%: 13.5 ± 5.3 g/kg/d; p = 0.3). Percent of feedings from donor milk was similar based on maternal HIV status (positive: 31 ± 25%; negative: 36 ± 29%; p = 0.4), as was percent of feedings as mother’s milk (positive: 53 ± 35%; negative: 58 ± 30%; p = 0.4). Calorie intake increased markedly during the first two weeks and then plateaued (p < 0.0001). Conclusions Donor milk feedings in higher proportions did not further impair growth of infants managed in a South African combined neonatal intensive and secondary high care unit with growth rates already below reference ranges. The provision of donor milk contributed to feedings being composed of primarily human milk during the first month. Increasing early calorie intake may improve infant growth in this center

A model to predict disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD): the ADPKD Outcomes Model.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics. Methods: The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population. Results: A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles. Conclusions: The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice

CT-based online adaptive radiotherapy improves target coverage and organ at risk (OAR) avoidance in stereotactic body radiation therapy (SBRT) for prostate cancer

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. METHODS: Seven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student\u27s RESULTS: Seven patients completed 35 Fx\u27s of adaptive RT. Daily adaptation resulted in a statistically significant mean improvement in PTV V100 for all targets: [21.4 % ± 4.3 % for PTV 4000 (p \u3c 0.0001); 8.7 % ± 1.1 % for PTV 3625 (p \u3c 0.0001); and 11.5 % ± 3.1 % for PTV 2500 (p = 0.0013)]. Mean rectal D0.03 was significantly reduced by 38.8 cGy ± 5.95 cGy (p \u3c 0.0001) per fraction (194 cGy/5 fractions) compared to the initial plans. There was a modest increase in bladder dose of 10.9 cGy ± 4.93 cGy per fraction (p = 0.0424) for the adaptive plans. The adaptive plans met bladder constraints for every fraction. There were no statistically significant differences between sigmoid or bowel dose for adapted vs. initial plans. No patients experienced acute CTCAE grade ≥ 3 GI/GU adverse events (median F/U 9.5 months). All statistically significant differences were maintained in the presence and absence of rectal hydrogel spacer (p \u3c 0.05). CONCLUSIONS: CT-based online adaptive SBRT resulted in statistically significant and clinically meaningful improvements in PTV coverage and D0.03 cc dose to the rectum. A trial evaluating CT adaptive whole-pelvis prostate SBRT is underway