The fluid balance of special populations

In humans, sweating is one of the most variable routes of water loss. This thesis investigates sweat volumes and sweat composition during single training sessions. Chapter 4 investigates the variability of sweat losses and sweat composition between four training sessions. Forty-five able-bodied individuals (twenty males and twenty-five females) volunteered for the study and ranged in age from 18–65 years. Data was collected during the participants normal training sessions, consisting of various recreational pursuits. Sweat losses were determined by changes in body mass over the training session, and corrected for any fluid intake and urine losses during training. A sample of participants' sweat was obtained via adhesive gauze patches and analysed for sodium, potassium and chloride concentrations. Sweat samples were obtained from the shoulder, chest, forearm and thigh. The 95% confidence intervals determined from this study demonstrated the reliability of a single training session to estimate an individual's future hydration to within 2% of initial body mass. [Continues.

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Longitudinal patterns of unmet need for contraception among women living with HIV on antiretroviral therapy in South Africa

Objectives: Fertility intentions and contraceptive use are often not assessed in the context of clinical HIV care, representing a possible programming gap if women's family planning needs change over time. We aimed to identify longitudinal patterns of unmet need for contraception over a 12-month period among women living with HIV taking antiretroviral therapy (ART). Study design: 850 non-pregnant, HIV-positive women aged 18-35 on or initiating ART in Johannesburg, South Africa, were enrolled into a prospective cohort study in 2009-2010. Fertility intentions and contraceptive use were assessed during routine HIV care visits via an interviewer-administered questionnaire, and women were referred for on-site contraceptive counseling. We used group-based trajectory modeling to identify patterns of unmet need for contraception over 12 months, first in the entire population and then in a subset of recent ART initiators. Results: In the full population we identified four patterns of unmet need for contraception over one year. Half of the enrolled women were predicted to have a consistently high probability of unmet need, 22.9% a consistently low probability, 16.7% a decreasing probability, and 10.4% an increasing probability over time. Contraceptive method discontinuation and rapidly changing fertility intentions were the primary drivers of changing (increasing or decreasing) unmet need over follow-up. Results were similar in recent ART initiators. Conclusions: Half of women were estimated to have a high probability of unmet need that persisted over time, and more than a quarter were estimated to experience patterns of changing unmet need over 12 months. Family planning needs should be assessed more regularly in HIV-positive women to prevent unintended pregnancies and support safer conception among women trying to conceive

Trajectories of fertility intentions among women living with HIV in South Africa

Fertility intentions are thought to be dynamic among women of reproductive age, yet few studies have assessed fertility intentions over time among women with HIV. We examine temporal patterns of fertility intentions in women with HIV to assess the extent to which fertility intentions–and the corresponding need for safer conception and judicious antiretroviral therapy (ART) regimen selection–vary over time. 850 non-pregnant HIV-positive women aged 18–35 on or being initiated onto ART in Johannesburg, South Africa were enrolled into a prospective cohort study (2009–2010). Fertility intentions were assessed at enrollment and at 30-day intervals via an interviewer-administered questionnaire. We used group-based trajectory modelling to identify longitudinal patterns of fertility intentions over 12 months. We identified four patterns of fertility intentions, which we labelled “consistently low” (representing ∼60% of the population), “low and increasing” (∼23%), “high and increasing” (∼12%), and “high and decreasing” (∼5%). Our findings suggest that a single family-planning assessment at one time point is insufficient to fully identify and meet the reproductive needs of women with HIV. As HIV testing and treatment evolve in South Africa, routine screening for fertility intentions can offer important opportunities to optimize HIV treatment, prevention, and maternal and child health

Epidemiology and etiology of childhood pneumonia in 2010:estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries

BACKGROUND: The recent series of reviews conducted within the Global Action Plan for Pneumonia and Diarrhoea (GAPPD) addressed epidemiology of the two deadly diseases at the global and regional level; it also estimated the effectiveness of interventions, barriers to achieving high coverage and the main implications for health policy. The aim of this paper is to provide the estimates of childhood pneumonia at the country level. This should allow national policy–makers and stakeholders to implement proposed policies in the World Health Organization (WHO) and UNICEF member countries. METHODS: We conducted a series of systematic reviews to update previous estimates of the global, regional and national burden of childhood pneumonia incidence, severe morbidity, mortality, risk factors and specific contributions of the most common pathogens: Streptococcus pneumoniae (SP), Haemophilus influenzae type B (Hib), respiratory syncytial virus (RSV) and influenza virus (flu). We distributed the global and regional–level estimates of the number of cases, severe cases and deaths from childhood pneumonia in 2010–2011 by specific countries using an epidemiological model. The model was based on the prevalence of the five main risk factors for childhood pneumonia within countries (malnutrition, low birth weight, non–exclusive breastfeeding in the first four months, solid fuel use and crowding) and risk effect sizes estimated using meta–analysis. FINDINGS: The incidence of community–acquired childhood pneumonia in low– and middle–income countries (LMIC) in the year 2010, using World Health Organization's definition, was about 0.22 (interquartile range (IQR) 0.11–0.51) episodes per child–year (e/cy), with 11.5% (IQR 8.0–33.0%) of cases progressing to severe episodes. This is a reduction of nearly 25% over the past decade, which is consistent with observed reductions in the prevalence of risk factors for pneumonia throughout LMIC. At the level of pneumonia incidence, RSV is the most common pathogen, present in about 29% of all episodes, followed by influenza (17%). The contribution of different pathogens varies by pneumonia severity strata, with viral etiologies becoming relatively less important and most deaths in 2010 caused by the main bacterial agents – SP (33%) and Hib (16%), accounting for vaccine use against these two pathogens. CONCLUSIONS: In comparison to 2000, the primary epidemiological evidence contributing to the models of childhood pneumonia burden has improved only slightly; all estimates have wide uncertainty bounds. Still, there is evidence of a decreasing trend for all measures of the burden over the period 2000–2010. The estimates of pneumonia incidence, severe morbidity, mortality and etiology, although each derived from different and independent data, are internally consistent – lending credibility to the new set of estimates. Pneumonia continues to be the leading cause of both morbidity and mortality for young children beyond the neonatal period and requires ongoing strategies and progress to reduce the burden further

Physiological responses to a five-day adventure race:Continuous blood glucose, hemodynamics and metabolites the 2012 GODZone field-study

Background/Objective: Adventure racing is an ultra-endurance activity that imposes a unique multifaceted stress on the human body. The purpose of this field study was to examine the physiological responses to a 5-day adventure race. Methods: Eight competitors, two teams (1 female each) in the 2012 GODZone adventure race volunteered. Competitors trekked, cycled and paddled ∼326 km in ∼116 hours. Continuous glucose was measured the day before and throughout. Body mass, urinary solutes, and blood pressure and heart rate during resting, standing, and repeated squat-stand conditions, were assessed pre and post. Results: Despite no changes in mean blood glucose levels, there was increased glycemic variability (Standard deviation glucose; Pre: 0.5 ± 0.1 vs Race: 1.0 ± 0.2 mmol/L, p = 0.02) and periods of hypoglycemia (i.e., Min glucose Pre: 4.1 ± 0.3 vs Race: 3.6 ± 0.5 mmol/L, p = 0.05) during the race. After the race, the blood pressure during resting, standing and squat-stand conditions was significantly lower, by 14 ± 14 mmHg, 16 ± 15 mmHg and 18 ± 15 mmHg (all p < 0.05), respectively, with no change in heart rate. During five-days of adventure racing there is increased glycemic variability and more frequent periods of low blood glucose levels. Additionally, following the race pronounced hypotension is observed in competitors. Conclusion: We observed more frequent glucose fluctuations, lower glucose levels and significant perturbations in blood pressure control. Further research is warranted to examine the long-term impact of adventure racing on metabolic and cardiovascular function. Keywords: Ultraendurance, Glucose, Exercise, Adventure racing, Orthostati

Serious mental health diagnoses in children on the child protection register: a record linkage study.

Children with experience of maltreatment, abuse or neglect are known to have a higher prevalence of poor mental health. Child Protection Services identify children most at risk of harm and in need of intervention. Mental healthcare usage in this population is not well understood as registration data is not routinely linked to health records. We undertook data linkage to describe the population on the register, their mental healthcare usage and to calculate age- and sex-specific incidence rates of mental health outcomes. We analysed records from the Aberdeen City Council Child Protection Register and for mental health prescribing and referrals to child and adolescent mental health services (CAMHS) for the NHS Grampian region between 1st January 2012 and 31st December 2022. We identified 1,498 individuals with a Child Protection Register registration, of which 70% were successfully matched to health records. 20% of registrations occurred before birth and the median age of registration was 3 years. 10.1% of children with a registration ever received a mental health prescription, 5.1% for treatment of attention deficit hyperactivity disorder and 1.7% for treatment of depression. 18.9% received a referral to specialist outpatient Child and Adolescent Mental Health Services. Age- and sex- standardised incidence rates for mental health prescribing and referrals are higher for children with a child protection registration compared to the general population. Children identified as being at significant risk of harm and involved with child protection services are at greater risk of seeking or receiving professional mental health support than their peers. Clinical services should investigate additional ways to support this population’s mental well-being as a priority. Efforts to reduce the exposure of children to potentially harmful environments at a societal level should also be pursued

Radio galaxy evolution: what you can learn from a Brief Encounter

We describe the pitfalls encountered in deducing from classical double radio source observables (luminosity, spectral index, redshift and linear size) the essential nature of how these objects evolve. We discuss the key role played by hotspots in governing the energy distribution of the lobes they feed, and subsequent spectral evolution. We present images obtained using the new 74 MHz receivers on the VLA and discuss constraints which these enforce on models of the backflow and ages in classical doubles.Comment: invited talk at `Lifecycles of Radio Galaxies' workshop; eds John Biretta et a

Repression of cyclin D1 as a target for germ cell tumors

Metastatic germ cell tumors (GCT) are curable, however GCTs refractory to cisplatin-based chemotherapy have a poor prognosis. This study explores D-type cyclins as molecular targets in GCTs because all-trans-retinoic acid (RA)-mediated differentiation of the human embryonal carcinoma (EC) cell line NT2/D1 is associated with G1 cell cycle arrest and proteasomal degradation of cyclin D1. RA effects on D-type cyclins are compared in human EC cells that are RA sensitive or dually RA and cisplatin resistant (NT2/D1-R1) and in clinical GCTs that have both EC and mature teratoma components. Notably, GCT differentiation was associated with reduced cyclin D1 but increased cyclin D3 expression. RA was shown here to repress cyclin D1 through a transcriptional mechanism in addition to causing its degradation. The siRNA-mediated repression of individual cyclin D species resulted in growth inhibition in both RA sensitive and resistant EC cells. Only repression of cyclin D1 occurred in vitro and when clinical GCTs mature, implicating cyclin D1 as a molecular therapeutic target. To confirm this, the EGFR-tyrosine kinase inhibitor, Erlotinib, was used to repress cyclin D1. This inhibited proliferation in RA and cisplatin sensitive and resistant EC cells. Taken together, these findings implicate cyclin D1 targeting agents for the treatment of GCTs