Phenyleketonuria: a clinical and genetic study of British families

This thesis analyses 43 families with 86 cases of phenylketonuria, a rare metabolic disorder always associated with mental defect and occurring in about 4 per 100,000 persons, defines the symptomatology, discusses the pathology and biochemistry, proves the inheritance of the disease as a Mendelian recessive Character, records the presence of other mental disorders in the families and reviews the literature

The role of finance in the decision-making of higher education applicants and students: findings from the Going into Higher Education Research study (BIS Research Paper No.9)

"This report summarises findings from the Going into HE research project. From the outset, the aim has been to develop a clear understanding of: the role and importance of finance in the decision-making process of English-domiciled people from different groups who are considering entering full-time Higher Education (HE) in the UK; and the impact of the support arrangements on their decisions. When taken alongside quantitative studies on HE participation and student finances, also published by DIUS/BIS, the qualitative research presented here contributes to an overall assessment of current student finance arrangements and should help to inform future developments." - exec. summary

Nurses' views of using computerized decision support software in NHS Direct

Background. Nurses working in NHS Direct, the 24-hour telephone advice line in England, use computerized decision support software to recommend to callers the most appropriate service to contact, or to advise on self-care. Aims. To explore nurses' views of their roles and the computerized decision support software in NHS Direct. Methods. Qualitative analysis of semi-structured interviews with 24 NHS Direct nurses in 12 sites. Findings. Nurses described both the software and themselves as essential to the clinical decision-making process. The software acted as safety net, provider of consistency, and provider of script, and was relied upon more when nurses did not have clinical knowledge relevant to the call. The nurse handled problems not covered by the software, probed patients for the appropriate information to enter into the software, and interpreted software recommendations in the light of contextual information which the software was unable to use. Nurses described a dual process of decision-making, with the nurse as active decision maker looking for consensus with the software recommendation and ready to override recommendations made by the software if necessary. However, nurses' accounts of the software as a guide, prompt or support did not fully acknowledge the power of the software, which they are required to use, and the recommendation of which they are required to follow under some management policies. Over time, the influence of nurse and software merges as nurses internalize the software script as their own knowledge, and navigate the software to produce recommendations that they feel are most appropriate. Conclusions. The nurse and the software have distinct roles in NHS Direct, although the effect of each on the clinical decision-making process may be difficult to determine in practice

OR13-3 Effects of Iron Isomaltoside versus Ferric Carboxymaltose on Hormonal Control of Phosphate Homeostasis: The PHOSPHARE-IDA04/05 Randomized Controlled Trials

Iron isomaltoside (IIM) and ferric carboxymaltose (FCM) are newer intravenous iron preparations that can be administered in high-doses to rapidly correct iron deficiency anemia (IDA). FCM can cause hypophosphatemia due to fibroblast growth factor 23 (FGF23) mediated renal phosphate wasting, which has been associated with osteomalacia, but the comparative effects of IIM are unknown. In two separate, identically designed, open label randomized controlled trials, we 1:1 randomized 245 adults with IDA to receive IIM (single infusion of 1000 mg) or FCM (FDA-approved dosing schedule: 2 infusions of 750 mg administered 1 week apart). We compared the incidence, severity and duration of hypophosphatemia, and effects on renal phosphate excretion, FGF23, PTH, vitamin D, and biomarkers of bone turnover measured in blood and urine samples collected at study visits at baseline (day 0) and on days 1, 7, 8, 14, 21, and 35. In pooled analyses of both trials, the incidence of hypophosphatemia 35 days. FCM but not IIM also induced changes in vitamin D and calcium homeostasis that triggered secondary hyperparathyroidism, which likely contributed to persistence of hypophosphatemia. Consistent with case reports of pathological fractures following FCM use, FCM also induced significant elevations of biomarkers of bone turnover that are associated with osteomalacia

Reliability and validity of the running anaerobic sprint test (RAST) in soccer players.

To investigate the validity and relative and absolute reliability of the Running Anaerobic Sprint Test (RAST) in ama teur soccer players. Cross-sectional experimental design with an element of repeated measures. Twenty three males completed the RAST on two occasions and a Wingate test (WAnT) as criterion measure of anaero bic power. Criterion validity for the RAST was strong for peak power (r = 0.70, p < 0.001) and average power (r = 0.60, p = 0.002); however, the RAST significantly underestimated peak power compared to WAnT. The RAST showed very good relative reli ability for average power, ICC = 0.88 and good relative reliability for peak power, ICC = 0.72. Assessment of absolute reliability highlighted that although when averaged across a group, test and re-test scores will be similar, when monitoring individuals an individual's retest score may range between 0.81 and 1.2 times the original value for peak power and between 0.9 and 1.16 for average power. The RAST is a practicable field test to estimate levels of average anaerobic power. However, the results show that the RAST is not sensitive enough to detect strongly individual changes below 20 % and is therefore not recommended to continually monitor an individual's anaerobic power. Also, if true measures of peak power are required the RAST test is limited

Serum osmolarity and haematocrit do not modify the association between the impedance index (Ht2/Z) and total body water in the very old: The Newcastle 85+ Study

Bioelectrical impedance is a non-invasive technique for the assessment of body composition; however, information on its accuracy in the very old (80+ years) is limited. We investigated whether the association between the impedance index and total body water (TBW) was modified by hydration status as assessed by haematocrit and serum osmolarity. This was a cross-sectional analysis of baseline data from the Newcastle 85+ Cohort Study. Anthropometric measurements [weight, height (Ht)] were taken and body mass index (BMI) calculated. Leg-to-leg bioimpedance was used to measure the impedance value (Z) and to estimate fat mass, fat free mass and TBW. The impedance index (Ht2/Z) was calculated. Blood haematocrit, haemoglobin, glucose, sodium, potassium, urea and creatinine concentrations were measured. Serum osmolarity was calculated using a validated prediction equation. 677 men and women aged 85 years were included. The average BMI of the population was 24.3±4.2kg/m2 and the prevalence of overweight and obesity was 32.6% and 9.5%, respectively. The impedance index was significantly associated with TBW in both men (n=274, r=0.76, p<0.001) and women (n=403, r=0.96, p<0.001); in regression models, the impedance index remained associated with TBW after adjustment for height, weight and gender, and further adjustment for serum osmolarity and haematocrit. The impedance index values increased with BMI and the relationship was not modified by hydration status in women (p=0.69) and only marginally in men (p=0.02). The association between the impedance index and TBW was not modified by hydration status, which may support the utilisation of leg-to-leg bioimpedance for the assessment of body composition in the very old

Salvinorin B Meth­oxy­methyl Ether

The title compound [MOM-SalB; systematic name: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(3-fur­yl)-9-meth­oxy­meth­oxy-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octa­hydro-1H-benzo[f]isochromene-7-carboxyl­ate], $C_{23}H_{30}O_8$, is a deriv­ative of the κ-opioid salvinorin A with enhanced potency, selectivity, and duration of action. Superimposition of their crystal structures reveals, surprisingly, that the terminal C and O atoms of the MOM group overlap with the corresponding atoms in salvinorin A, which are separated by an additional bond. This counter-intuitive isosterism is possible because the MOM ether adopts the 'classic anomeric' conformation (gauche–gauche), tracing a helix around the planar acetate of salvinorin A. This overlap is not seen in the recently reported structure of the tetra­hydro­pyranyl ether, which is less potent. The classic anomeric conformation is strongly favoured in alk­oxy­methyl ethers, but not in substituted acetals, which may contribute to their reduced potency. This structure may prove useful in evaluating models of the activated $\kappa$-opioid receptor

Interactions of osteoprogenitor cells with a novel zirconia implant surface

Background: This study compared the in vitro response of a mouse pre-osteoblast cell line on a novel sandblasted zirconia surface with that of titanium. Material and Methods: The MC3T3-E1 subclone 4 osteoblast precursor cell line was cultured on either sandblasted titanium (SBCpTi) or sandblasted zirconia (SBY-TZP). The surface topography was analysed by three-dimensional laser microscopy and scanning electron microscope. The wettability of the discs was also assessed. The cellular response was quantified by assessing the morphology (day 1), proliferation (day 1, 3, 5, 7, 9), viability (day 1, 9), and migration (0, 6, 24 h) assays. Results: The sandblasting surface treatment in both titanium and zirconia increased the surface roughness by rendering a defined surface topography with titanium showing more apparent nano-topography. The wettability of the two surfaces showed no significant difference. The zirconia surface resulted in improved cellular spreading and a significantly increased rate of migration compared to titanium. However, the cellular proliferation and viability noted in our experiments were not significantly different on the zirconia and titanium surfaces. Conclusions: The novel, roughened zirconia surface elicited cellular responses comparable to, or exceeding that, of titanium. Therefore, this novel zirconia surface may be an acceptable substitute for titanium as a dental implant material

A Regional Model Study of High Latitude Tropospheric Ozone and its Precursors.

The Arctic has warmed disproportionately relative to mid-latitudes over recent decades. This warming is predominantly controlled by radiative forcing from well-mixed greenhouse gases, amplified by efficient Arctic climate feedbacks. However, warming from changes in short-lived climate pollutants (SLCPs), such as tropospheric ozone, have been shown to contribute substantially to Arctic warming, whilst also degrading air quality. Arctic SLCP abundances are controlled by long-range transport from mid-latitudes, and by local sources within the Arctic. At present, high latitude emissions of SLCPs and ozone precursors (e.g nitrogen dioxide [NO2]) are poorly quantified, with a paucity of in-situ observations. Using a regional chemistry transport model, this thesis aims to improve the understanding of processes controlling tropospheric ozone abundances and distributions in areas of limited in-situ observations at high latitudes. In western Siberia there is widespread negative bias in modelled tropospheric column NO2 when compared to satellite observations from May–August. Despite the large negative bias, the spatial correlations between model and observed NO2 columns suggest that the spatial pattern of NOx sources in the region is well represented. Scaling the two largest anthropogenic sectors (energy & transport) by a factor of 2 reduces column NO2 bias (fractional mean bias =−0.66 to −0.35). The findings in this thesis suggest that western Siberian ozone is more sensitive to anthropogenic emissions, particularly from the transport sector, and the contribution from fire emissions maximises in June and is largely confined to latitudes south of 60°N. Ozone dry deposition fluxes from the model simulations show that the dominant ozone dry deposition sink in the region is to forest vegetation, averaging 8.0 Tg of ozone per month. In Fairbanks, Alaska, modelled surface ozone is overestimated during springtime, with an interplay between ozone being vertically mixed down from ozone-rich air above and subsequent ozone loss to NO (O3 + NO = NO2) dominating ozone abundances, suppressing surface ozone. This also leads to significant overestimations in surface NO2. Sensitivity studies tested modelled ozone sensitivity to Fairbanks NOx emissions and model upper boundary conditions. Results suggest that upper troposphere ozone is sensitive to a 20% reduction in initial boundary condition ozone, which brings the values in-line with observations. Whilst a doubling of NOx emissions from within Fairbanks improves the model ozone bias at the surface, but still leads to model overestimation above the boundary layer

Reverse genetics in Candida albicans predicts ARF cycling is essential for drug resistance and virulence

Peer reviewedPublisher PD