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Pioneering of condensed matter physics relates to various factors of electronic correlations. Exploring new materials, always achieve important roles to develop the understanding of magnetism in correlated matter. Rare-earth-based compounds especially Cerium-based inter-metallics display different types of interesting properties and the reason behind these fascinating properties is the strongly correlated nature of these materials. In broadening our level of understanding on correlated materials especially on low temperatures, we aim to set a report on the compound of CeRuAl. Physical properties (magnetic, transport and electronic) of CeRuAl are measured for the temperature ranges 400 K to 0.5 K and in the magnetic field up to 7 T. It is observed that the Sommerfeld coefficient, which is calculated from the measurements of heat capacity, has the value of γ = 62 mJ/mol K2. At temperature 1.1 K, this compound CeRuAl shows mixed valent behavior. At the lower temperature range (0.9 K to 0.4 K) with applied field up to 0.5 T, the superconductivity property is evident. Absence of quick rise in low-temperature resistivity indicates that the gap formation in the electronic density of states does not exist. [ABSTRACT FROM AUTHOR]

An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 'DSDnet' was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case. [ABSTRACT FROM AUTHOR]

Global interest in studying biochar stems from its ability to sequester carbon in soil and render nutrients and moisture more readily available to root systems. Therefore, a bibliometric analysis was conducted to investigate global scientific publications related to biochar research, providing insight into the number of articles published, journal platforms, subjects, citations, and overall trends. The primary databases employed were the Web of Science and Science Citation Index. A total of 1,697 articles published between 2000 and 2015 were evaluated. This systematic bibliometric analysis will assist research groups and individuals to understand global biochar research trends and focus future research. The influence of biochar on soil, plants, and the environment continues to require greater attention. [ABSTRACT FROM AUTHOR]

Amendment of soil with biochar has been shown to enhance fertility and increase crop productivity, but the specific influence of biochar on soil workability remains unclear. Select physico-mechanical and chemical properties of clay loam and sandy loam soils were measured after amendment with wood-derived biochar of two particle size ranges (0.5-425 and 425- 850 µm) at five dosages ranging from 0.5 to 10% dry weight. Whereas the clay loam soil workability decreased when the finer wood-derived biochar was applied at rates of 6 or 10%, soil fertility was not enhanced. The sandy loam soil, due to Proctor compaction, significantly decreased in bulk density with 6 and 10% wood-derived biochar amendments indicating higher soil resistance to compaction. [ABSTRACT FROM AUTHOR]

This study aimed to compare economically between the impact of three light sources on the growth performance of Japanese quail. The experiment of this study lasted 56 days and included 126 one day old chicks divided in 3 groups X 3 replicates each of 4 males and 10 females. They were raised in battery cages under similar managerial conditions, subjected to light from 60 watt incandescent, 40-watt fluorescent and 26 watt saving lamps for 8 light hours/ daily with intensity of 14-16 Lux during the first three days and 4-6 Lux during the rest of the experiment. They were individually weighed every week, while the body weight gain (BWG) was calculated biweekly. The averages of female body weight (BW) and age at sexual maturity were determined. Similarly, the averages of feed consumption (FC) and feed conversion ration (FCR) were also determined. At the end of the experiment, 6-fasted females were slaughtered and 6 blood samples per group were taken to determine some blood components and to estimate the carcass quality. The lighting costs included both of the power cost (kw/LE) and the value of the lamp depreciation, (lighting hours / life span of the lamp X lamp price LE). The results revealed that: 1-The average BW of females exposed to light from fluorescent (FLU,T1) was significantly lighter at 2, 4, 6 and 8 weeks than those of the control (INC) and the saving lamps (T2). 2- The average Total BWG (204.76 g) in T1 (flu) decreased significantly than those 214.61 and 216.85g of T2 and the control, respectively. 3- The least average FC (692.30 g) was recorded in T2 (saving) decreasing significantly than those 712.60 and 721.47 g of T1 and the control, respectively. 4- The best average FCR (3.12) was recorded in T2 improving significantly than that 3.42 of T1 and insignificantly than 3.22 of the control. 5- The least average of females BW at sexual maturity (204.48 g) was found in T1 decreasing significantly than those 212.42 and 220.04 g of T2 and the control, respectively. 6- The minimal age at sexual maturity was found in T2 (saving) decreasing significantly than that of the control and T1 (flu). 7- The use of the saving lamps minimized the lighting costs by 56.43% than that of control. Taking in consideration the above mentioned advantages, it could be concluded that the use of saving lamp is highly recommended for raising Japanses Quail birds economically. [ABSTRACT FROM AUTHOR]

Background: Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. Objective: To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. Methods: We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). Results: 76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p < 0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n = 3) and lymphadenitis (n = 1). Conclusion: Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies. [ABSTRACT FROM AUTHOR]

An immobilized TiO2 photocatalyst with a high specific surface area was prepared on stainless steel woven meshes in order to be used packed in layers for water purification. Immobilization of such a complex shape needs a special coating technique. For this purpose, dip coating and electrophoretic deposition (EPD) techniques were used. The EPD technique gave the TiO2 coating films a better homogeneity and adhesion, fewer cracks, and a higher ·OH formation than the dip coating technique. The woven mesh structure packed in layers guaranteed an efficient light-penetration in water treatment reactor. A simple equation model was used to describe the distribution of light through the mesh layers in the presence of absorbing medium (e.g., colored water with humic acids). Maximum three or four coated meshes were enough to harvest the solar UV light from 300 nm to 400 nm with a high penetration efficiency. The separation distance between the mesh layers played an important role in the efficiency of solar light penetration through the coated mesh layers, especially in case of colored water contaminated with high concentrations of humic acid. [ABSTRACT FROM AUTHOR]

This paper reports the properties of concrete containing recycled coarse aggregate (RCA) sources from local construction and demolition (C&D) wastes and fly ash (FA) sourced from Western Australia (WA). The RCA is used as 25, 50, 75, and 100% (by weight) replacement of natural coarse aggregate (NCA). In addition, the effect of 40% (by weight) class F fly ash as partial replacement of cement on the properties of recycled aggregate concrete is also evaluated. The properties of concrete evaluated are the compressive strength, indirect tensile strength, flexural strength, and water absorption. All properties are measured at 7, 28, 56, and 91 days. The results show that better compressive, tensile, and flexural strength of concrete containing 25% RCA as partial replacement of NCA can be obtained in recycled aggregate concrete. However, in the case of recycled aggregate concretes containing 40% fly ash, the compressive strength at later ages, such as at 56 and 91 days is increased but the indirect tensile and flexural strengths are decreased at all ages. It is observed that the water absorption is decreased as RCA content increased. It is also observed that the water absorption is decreased significantly in recycled aggregate concretes containing 40% fly ash at all ages. [ABSTRACT FROM AUTHOR]

c-Myc is a proto-oncogenic transcription factor and its rapid turnover mediated by the ubiquitin-proteasome system is critical for maintaining normal cellular homeostasis. Multiple ubiquitin ligases have been assigned for c-Myc regulation till date. However, the available data suggest for the possible existence of additional E3 ligase(s). Here, we report a new E3 ligase for c-Myc, the carboxyl terminus of Hsc70-interacting protein or CHIP, which is a chaperone-associated Ubox-containing E3 ligase. In this report, we show that CHIP interacts and ubiquitinates c-Myc, thus targeting it for proteasome-mediated degradation. Overexpression of CHIP could accelerate the turnover rate of c-Myc protein. Conversely, knockdown of CHIP by RNAi stabilizes endogenous c-Myc. The interaction between CHIP and c-Myc depends on the N-terminally located tetratricopeptide repeats of CHIP, which has been implicated as a chaperone-binding motif. Inhibition of Hsp90 chaperone activity by 17-N-allylamino-17-demethoxygeldanamycin reduces c-Myc protein level. We found that the association between CHIP and c-Myc is dependent on the chaperones; particularly Hsp70. CHIP antagonizes the transcriptional activity of c-Myc and decreases the abundance of the transcripts of its target genes. Overall, CHIP-knockdown increases malignant behavior of C6 glioma cells. To the best of our knowledge, this is the first report of c-Myc being regulated by a bona-fide chaperone-associated E3 ligase in HEK293 as well as glioma cells. Because CHIP has been reported earlier to be negatively regulating Akt1, BCR-ABL and hTERT, and now c-Myc, the present study may strengthen the view that CHIP acts as a tumor suppressor. [ABSTRACT FROM AUTHOR]

This paper reports the properties of concrete containing recycled coarse aggregate (RCA) sources from local construction and demolition (C&D) wastes and fly ash (FA) sourced from Western Australia (WA). The RCA is used as 25, 50, 75, and 100% (by weight) replacement of natural coarse aggregate (NCA). In addition, the effect of 40% (by weight) class F fly ash as partial replacement of cement on the properties of recycled aggregate concrete is also evaluated. The properties of concrete evaluated are the compressive strength, indirect tensile strength, flexural strength, and water absorption. All properties are measured at 7, 28, 56, and 91 days. The results show that better compressive, tensile, and flexural strength of concrete containing 25% RCA as partial replacement of NCA can be obtained in recycled aggregate concrete. However, in the case of recycled aggregate concretes containing 40% fly ash, the compressive strength at later ages, such as at 56 and 91 days is increased but the indirect tensile and flexural strengths are decreased at all ages. It is observed that the water absorption is decreased as RCA content increased. It is also observed that the water absorption is decreased significantly in recycled aggregate concretes containing 40% fly ash at all ages. [ABSTRACT FROM AUTHOR]

The equation of fiber motion in dusty fluid turbulent flow has been derived in terms of correlation tensors of second order. In presence of dust particles, mathematical modeling of fiber suspensions in the turbulent flow is discussed including the correlation between the pressure fluctuations and velocity fluctuations at two points of the flow field, where the correlation tensors are the functions of space coordinates, distance between two points and the time. [ABSTRACT FROM AUTHOR]

Background In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear. Aim The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations. Methods Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0·25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) ( n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3·5 nmol at day 4 and 9·5 nmol/l at day 22. Results In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3·5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3·5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9·5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases. Conclusion In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test. [ABSTRACT FROM AUTHOR]

Objective To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA. Design Three-year prospective study. Measurements Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls. Results Fifty-two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7·7 (0·99) and eight boys of 8·8 (0·67) years. Mean (SD) birth weight was 3·27 (0·49) and 3·10 (0·76) kg in girls and boys respectively. Height/weight SDS were 1·13/1·69 in girls and 1·69/1·88 in boys. Mean systolic/diastolic BP was 107·8/60·4 (50th–75th centile) in girls and 115·5/63·9 (75th–91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2·1 and 4·1 μmol/l, androstenedione 3·1 and 3·8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9·0 and 15·0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15·7 pmol/l in 27 girls, compared with 5·0 pmol/l in normal girls aged 5–8 years. Conclusions Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development. [ABSTRACT FROM AUTHOR]

This paper presents some experimental results on the corrosion durability of cracked reinforced concrete beams made with plain mortar and strain hardening fi bre-reinforced cementitious composites (SHFRCCs) containing polyethylene and steel-polyethylene hybrid fi bres. All beams are subjected to cyclic wetting and drying using water containing 3% sodium chloride (NaCl). In addition, an external potential is also applied to the reinforcement to accelerate the corrosion. Corrosion of steel bars is monitored through a pair of sensors attached to the reinforcing bar in each beam. Test results show that beams containing SHFRCC material exhibited better corrosion protection than that of plain mortar beams. Among all specimens, beams containing hybrid steelpolyethylene fi bre-reinforced SHFRCC exhibited the best corrosion protection. [ABSTRACT FROM AUTHOR]

It has been shown that cell cycle genes play an important role in the coordination of chondrocyte proliferation and differentiation. The inhibitory effects of glucocorticoids (GCs) on chondrocyte proliferation are consistent with GCs disrupting cell cycle progression and promoting cell cycle exit. Cyclin-dependent kinase inhibitors (CDKIs) force cells to exit the cell cycle and differentiate, and studies have shown that expression of the CDKI p21(CIP1/WAF1) is increased in terminally differentiated cells. In this study, p21 mRNA and protein expression was increased during chondrocyte differentiation and after exposure to dexamethasone (Dex, 10(-6 )M) in murine chondrogenic ATDC5 cells. In 4-week-old mice lacking a functional p21 gene, Dex caused a reduction in body weight compared to saline control null mice, but this was consistent with the reduction in body weight observed in Dex-treated wild-type littermates. In addition, p21 ablation had no effect on the reduction in width of the growth plate or reduced mineral apposition rate in Dex-treated mice. However, an alteration in growth rate and epiphyseal structure is evident when comparing p21(-/-) and wild-type mice. These findings suggest that p21 does not directly contribute to GC-induced growth retardation in vivo but is involved in the maintenance of the growth plate. [ABSTRACT FROM AUTHOR]

Effects of temperature and the aspect ratio on the electron field emission properties of vertically aligned carbon nanofibers in thin-film form were studied in detail. Vertically aligned carbon nanofibers have been synthesized on silicon substrates via a direct current plasma enhanced chemical vapor deposition technique. Surface morphologies of the films were studied by an atomic force microscope. It was found that the length of the nanofibers increased and the diameter decreased as the thickness of the Ni catalyst film decreased. The threshold field for the electron field emission was found to be in the range from 4.3 to 5.4 V/μm for carbon nanofibers having different aspect ratios. The threshold field for carbon nanofibers having diameter ∼ 200 nm and aspect ratio ∼7.5 was found to decrease from 4.8 to 2.1 V/μm when the temperature was raised from 27 to 350 °C. This dependence was due to the change in work function of the nanofibers with temperature. The field enhancement factor, the current density and the effective work function were calculated and used to explain the emission mechanism. [ABSTRACT FROM AUTHOR]

Background: Conjoint analysis involves the measurement of consumer preferences between choice alternatives. Aims and objectives: To investigate the use of conjoint analysis in facilitating and understanding choice of growth hormone injection devices. Method and subjects: 56 patients and their parents participated in an electronic, computer-based interview. The interview took a median time of 18 mm (range 12-30) and allowed an immediate matching of injection devices to the family's preferences. Results: Amongst the key drivers of choice, lack of bruising was rated highest and designated an index of 100. Compared to this, the remaining attributes in order of desirability were: auto-injector (98), lack of pain (93), lightweight (88), silent (82), ready-mixed (77), ease of holding (69), telephone helpline (66), needle-free (62), small size (60), nurse support (47), hidden needle (45), stored in fridge (13) and home delivery 161. Out of the 17 families who had already chosen a device previously by discussion with the clinic nurse, the computer model placed their device either as first or second out of seven devices tested. Conclusion: Adaptive or interactive conjoint analysis applied at the patient level can facilitate the choice- making process whilst providing an insight into the relative importance of the key features that influence choice. [ABSTRACT FROM AUTHOR]

The birth of a new baby is one of the greatest wonders of nature and one of the most exciting events known to man. The first question that is usually posed by the mother or father is "is it a boy or a girl?"; without this information the new parents cannot even formulate the second question which is usually "is he/she alright?". It is no wonder that the birth of a child with complex genital anomalies where the sex of rearing is uncertain at birth, presents difficult clinical and ethical issues. [ABSTRACT FROM AUTHOR]

Summary aim To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover. method Prospective study over 16 weeks of children randomized to receive Pred (40 mg/m2 ) or Dex (6·5 mg/m 2 ) for the first 5 weeks as part of the MRC-ALL97/99 induction chemotherapy for acute lymphoblastic leukaemia (ALL). measurements Lower leg length velocity (LLLV) and weight, serum IGF-I, serum bone alkaline phosphatase (bALP) levels and creatinine-adjusted, urinary excretion of deoxypyridinoline cross-links (DPD). subjects Nineteen children (eight boys, 11 girls) with a median age of 5·9 years (range 2·6–13) and with a diagnosis of ALL. results At week 2 of therapy, median LLLV in the Dex group was -1·5 mm/week (range 0·7 to -2·1) and significantly lower than the LLLV in the Pred group which was -0·1 mm/week (range 0·20 to -0·28; P < 0·05). In the Dex group, LLLV remained lower at week 8 (med LLLV, -0·3 mm/week, range 0 to -1·3) compared to LLLV in the Pred group at 0·3 mm/week (range 0·2–1·0; P < 0·05). Body weight showed an increase after week 2 and reached a peak in both groups of children at week 6. The change in weight from baseline was greater in the Dex group than the Pred group reaching a maximum change by week 5 of 17·5% (range 5–25) and 8·7% (range -3 to 18), respectively ( P < 0·05). At presentation, median IGF-I level for the whole group was 83·5 µg/l (range 31·8–293). IGF-I levels fell markedly during Dex therapy and continued to remain lower than baseline. At weeks 4, 6 and 8, median change in IGF-I from baseline was lower in the Dex group than the Pred group. From week 1 to week 3, median change in bALP was 72% (range -8 to 304) in the Pred group, whereas in the Dex group change in bALP was -1% (range 23 to -28; P < 0·005). By week 3, median bALP was... [ABSTRACT FROM AUTHOR]

Background The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. Methods All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. Results Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identifi ed with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. Summary Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance. [ABSTRACT FROM AUTHOR]

In this study, the solution casting method was employed to prepare plasticized polymer electrolytes of chitosan (CS):LiCO2CH3:Glycerol with electrochemical stability (1.8 V). The electrolyte studied in this current work could be established as new materials in the fabrication of EDLC with high specific capacitance and energy density. The system with high dielectric constant was also associated with high DC conductivity (5.19 × 10−4 S/cm). The increase of the amorphous phase upon the addition of glycerol was observed from XRD results. The main charge carrier in the polymer electrolyte was ion as tel (0.044) < tion (0.956). Cyclic voltammetry presented an almost rectangular plot with the absence of a Faradaic peak. Specific capacitance was found to be dependent on the scan rate used. The efficiency of the EDLC was observed to remain constant at 98.8% to 99.5% up to 700 cycles, portraying an excellent cyclability. High values of specific capacitance, energy density, and power density were achieved, such as 132.8 F/g, 18.4 Wh/kg, and 2591 W/kg, respectively. The low equivalent series resistance (ESR) indicated that the EDLC possessed good electrolyte/electrode contact. It was discovered that the power density of the EDLC was affected by ESR. [ABSTRACT FROM AUTHOR]

BACKGROUND: Considerable debate exists on the epidemiology of genital anomalies. METHODS: All genital anomalies, excluding undescended testes, were identified from neonatal returns, stillbirth and infant death survey records, and returns relating to hospital admissions and linked to form infant profiles on a cohort of singleton births between 1988 and 1997 with follow up for a minimum of three years. FINDINGS: The mean genital anomaly prevalence rate in Scotland was calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9 per 1000 births in 1996. However, there was no evidence of a clear trend to an increasing prevalence of hypospadias, which constituted 73% of the anomalies studied. Logistic regression analysis of the data also showed this rate to be independently associated with being relatively small for gestational age (odds ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05). Infants born in deprived areas, as judged by the Carstairs deprivation score, were least likely to have a genital anomaly (OR 0.73, p < 0.01). INTERPRETATION: A new linked register of congenital genital anomalies in Scotland suggests that over a decade, the birth prevalence of genital anomalies has changed little. The associations between genital anomalies, maternal age, and socioeconomic deprivation require further study. [ABSTRACT FROM AUTHOR]

To provide an overview of the I‐CAH Registry. Following the successful roll‐out of the I‐DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I‐CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I‐CAH Registry are important tools for all stakeholders involved in the care of people with CAH. [ABSTRACT FROM AUTHOR]

Neonatal hepatitis and biliary hypoplasia are not recognised features of Williams syndrome. A case of Williams syndrome, presenting with neonatal conjugated hyperbilirubinaemia leading to an initial misdiagnosis is reported. [ABSTRACT FROM AUTHOR]

In this work, the binding mechanism between donepezil (DNP) and bovine serum albumin (BSA) was established using several techniques, including fluorimetry, UV- spectrophotometry, synchronous fluorimetry (SF), fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET) besides molecular docking study. The fluorescence quenching mechanism of DNP-BSA binding was a combined dynamic and static quenching. The thermodynamic parameters, binding forces, binding constant, and the number of binding sites were determined using a different range of temperature settings. Van't Hoff's equation was used to calculate the reaction parameters, including enthalpy change (ΔHο) and entropy change (ΔSο). The results pointed out that the DNP-BSA binding was endothermic. It was shown that the stability of the drug-protein system was predominantly due to the intermolecular hydrophobic forces. Additionally, the site probing method revealed that subdomain IIA (Site I) is where DNP and BSA's binding occurs. This was validated using a molecular docking study with the most stable DNP configuration. This study might help to understand DNP's pharmacokinetics profile and toxicity as well as provides crucial information for its safe use and avoiding its toxicity. [ABSTRACT FROM AUTHOR]

Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer. Both in vitro and in vivo anti-inflammatory activities of the synthesized compounds were assessed relative to the positive standards: celecoxib and indomethacin. The in vitro enzymatic and transcription inhibitory actions of all the synthesized compounds were tested against cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and 5-lipoxygenase (LOX) and the in vivo gene expression of Interleukin-1, interleukin 10, and Tumor Necrosis Factor-α (TNF-α) were determined. The IC50 against COX-1 and COX-2 enzymes obtained by the immunoassay test revealed promising activities of sixteen compounds with selectivity indices higher than 100-fold COX-2 selectivity. Out of those, four compounds revealed selectivity indices comparable to celecoxib as a reference drug. Furthermore, all the tested compounds inhibited LOX with an IC50 in the range of 1.59–3.11 µM superior to that of the reference drug used; zileuton (IC50 = 3.50 µM). Consequently, these results highlight the promising LOX inhibitory activity of the tested compounds. The obtained in vivo paw edema results showed high inhibitory percentage for the compounds 9a, 9b, and 11a with the significant lower TNF-α relative mRNA expression for compounds 5a, 5d, 9a, 9b, 12d, and 12e. Finally, in silico docking of the most active compounds (5b, 5d, 9a, 9b) against COX2 enzymes presented an acceptable justification of the obtained in vitro inhibitory activities. As a conclusion, Compounds 5b, 5d, 9a, 9b, and 11b showed promising results and thus deserves further investigation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a statement by the British Paediatric and Adolescent Bone Group on vitamin D deficiency.

Background:Predicting disease progression over time is challenging despite the available literature data.Aim: To assess whether baseline clinical variables of MS patients would predict the conversion to progressive phase of the disease.Materials & methods: Utilizing the national MS registry, patients who had relapsing onsets and had confirmed EDSS score at baseline and follow-up visits were included. Primary progressive MS and CIS patients were excluded. Clinical variables (gender, age at onset, disease duration, number of relapses, EDSS score) were collected. The end point was conversion to secondary progressive MS. Chi Square and multivariable logistic regression were used to determine the influence of clinical variables on disease progression.Results:Data of 803 MS patients with relapsing onset were analyzed. Eighty five (10.6%) patients reached the end point. The risk of disease progression was significantly higher in men (p= 0.015), in patients who developed MS ≥ 40 years of age (p= 0.041) and who had ≥ 3 relapses during their disease course (p< 0.001). Spinal cord presentation at onset was predictive of progression (aOR = 2.01;p= 0.06) while optic neuritis at onset was associated with lower risk of progression (aOR = 0.30;p= 0.03). EDSS score at first visit did not influence disease progression when tested at 2 different cutoffs (EDSS < 4 vs. ≥ 4 and EDSS < 6 vs. ≥ 6) using multivariable logistic regression analysis (p= 0.960 andp= 0.866), respectively.Conclusion: Men and patients who presented at age 40 yeas or beyond had increased risk of MS progression. Spinal cord symptoms at onset and 3 or more relapses were predictive of progression. [ABSTRACT FROM PUBLISHER]

Introduction Pulmonary arterial hypertension (PH) is commonly found in patients with mitral valve diseases. Most of the drugs used for PH treatment are nonselective pulmonary vasodilators that may cause a modest decrease in pulmonary arterial pressure, but they may cause a marked decrease in systemic vascular resistance as well, which leads to hypotension and a decrease in perfusion of vital organs. Inhaled drugs such as milrinone and nitroglycerine may be safer as a large dose of the drug can selectively target the pulmonary circulation, which leads to a reduction of their systemic adverse effects. Aim This double-blind, randomized study compared milrinone inhalation versus nitroglycerin inhalation on pulmonary artery pressure and other hemodynamics in postoperative patients immediately after mitral valve replacement surgery. Patients and methods A total of 40 participants with isolated mitral stenosis or isolated mitral incompetence or their combination plus PH [mean pulmonary artery pressure (mPAP) >40 mmHg] scheduled for mitral valve replacement were interviewed. Immediately postoperatively in the ICU, we randomized the patients into two groups, with 20 patients each. Group A consisted of 20 patients who received milrinone inhalation, whereas group B consisted of 20 patients who received nitroglycerine inhalation. Hemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, central venous pressure, pulmonary artery systolic pressure, pulmonary diastolic pressure, mPAP, fractional shortening, ejection fraction, and pressure of oxygen/fraction of inspired oxygen ratio) were recorded in both groups at three time points: T1, before drug delivery; T2, just after drug delivery; and T3, just before extubation. Results The study showed that both milrinone and nitroglycerin inhalation caused a marked reduction in systolic, diastolic, and mPAPs without causing any hemodynamic deterioration effects on systolic, diastolic, or mean arterial pressures. Conclusion Although both milrinone and nitroglycerin inhalation proved to be effective pulmonary artery vasodilators that avoided systemic adverse effects, nitroglycerin inhalation is a less expensive, easily obtained drug that can serve as an inhaled pulmonary vasodilator in patients with mitral valve diseases and PH following mitral valve replacement surgeries. [ABSTRACT FROM AUTHOR]

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC50 values of 0.09–0.14 µM) with significant 15-LOX inhibitory activities (IC50s 1.96 to 3.52 µM). Upon investigation of their in vivo anti-inflammatory activities and ulcerogenic profiles, these compounds showed activity patterns equivalent or more superior to diclofenac and/or celecoxib. Intriguingly, the most active compounds were more effective than diclofenac in suppressing monocyte-to-macrophage differentiation and inflammatory cytokine production by activated macrophages, as well as their ability to induce macrophage apoptosis. The latter finding potentially adds a new dimension to the previously reported anti-inflammatory mechanisms of similar compounds. These compounds were effectively docked into COX-2 and 15-LOX active sites. Also, in silico predictions confirmed the appropriateness of these compounds as drug-like candidates. [ABSTRACT FROM AUTHOR]

Background. Most child deaths from motor vehicle accidents (MVAs) occur in low- and middle-income countries. Effective measures to protect children involved in MVAs include wearing age-appropriate child restraints and being seated in the rear of the vehicle. Methods. A descriptive study was used to assess use of child restraints, seating positions of children, driver restraint and vehicle overloading in Bloemfontein in 2007. Two pairs of observers stood at selected sites recording these findings. The study was done over a period of 1 month. Results. A total of 512 children in 374 vehicles were assessed. Just over a third of the children were seated on the front seat of the vehicle, and 14.1% were seated on other people's laps (73.6% of these were on the front seat). Restraints were used by 8.8% of children and 17.4% of drivers; 10 times more children used restraints if the driver was restrained versus not restrained. Between 9.3% and 20.4% of vehicles were assessed as being overloaded with passengers. Conclusion. The safety of child passengers in Bloemfontein in the event of an MVA is threatened by poor adherence to basic safety measures. Enforcement of correct seating position and use of child restraints will prevent unnecessary deaths, disabilities and suffering of child passengers injured in the event of an MVA. Driver motivation and responsibility is important in achieving safer seating of children in motor vehicles. [ABSTRACT FROM AUTHOR]

Fossil fuels provide a significant fraction of the global energy resources, and this is likely to remain so for several decades. Carbon dioxide (CO) emissions have been correlated with climate change, and carbon capture is essential to enable the continuing use of fossil fuels while reducing the emissions of CO into the atmosphere thereby mitigating global climate changes. Among the proposed methods of CO capture, oxyfuel combustion technology provides a promising option, which is applicable to power generation systems. This technology is based on combustion with pure oxygen (O) instead of air, resulting in flue gas that consists mainly of CO and water (HO), that latter can be separated easily via condensation, while removing other contaminants leaving pure CO for storage. However, fuel combustion in pure O results in intolerably high combustion temperatures. In order to provide the dilution effect of the absent nitrogen (N) and to moderate the furnace/combustor temperatures, part of the flue gas is recycled back into the combustion chamber. An efficient source of O is required to make oxy-combustion a competitive CO capture technology. Conventional O production utilizing the cryogenic distillation process is energetically expensive. Ceramic membranes made from mixed ion-electronic conducting oxides have received increasing attention because of their potential to mitigate the cost of O production, thus helping to promote these clean energy technologies. Some effort has also been expended in using these membranes to improve the performance of the O separation processes by combining air separation and high-temperature oxidation into a single chamber. This paper provides a review of the performance of combustors utilizing oxy-fuel combustion process, materials utilized in ion-transport membranes and the integration of such reactors in power cycles. The review is focused on carbon capture potential, developments of oxyfuel applications and O separation and combustion in membrane reactors. The recent developments in oxyfuel power cycles are discussed focusing on the main concepts of manipulating exergy flows within each cycle and the reported thermal efficiencies. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Longitudinal bone growth is a tightly regulated process that relies on complex synchronized mechanisms at the growth plate. Chronic paediatric inflammatory diseases are well accepted to lead to growth retardation and this is likely due to raised inflammatory cytokine levels and reduced growth hormone (GH)/insulin-like growth factor-1 (IGF-I) signalling. The precise cellular mechanisms responsible for this inhibition are unclear and therefore in this article, we will review the potential interactions between inflammatory cytokines and the GH/IGF-I axis in the regulation of bone growth. In particular, we will emphasis the potential contribution of the suppressors of cytokine signalling (SOCS) proteins, and in particular SOCS2, in mediating this process. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) are commonly used anti-inflammatory drugs, but long-term use can result in marked growth retardation in children due to their actions on growth plate chondrocytes. To gain an insight into the mechanisms involved in GC-induced growth retardation, we performed Affymetrix microarray analysis of the murine chondrogenic cell line ATDC5, incubated with 10-6 M dexamethasone (Dex) for 24 h. Downregulated genes included secreted frizzled-related protein and IGF-I, and upregulated genes included serum/GC-regulated kinase, connective-tissue growth factor, and lipocalin 2. Lipocalin 2 expression increased 40-fold after 24-h Dex treatment. Expression increased further after 48-h (75-fold) and 96-h (84-fold) Dex treatment, and this response was Dex concentration dependent. Lipocalin 2 was immunolocalized to both proliferating and hypertrophic growth plate zones, and its expression was increased by Dex in primary chondrocytes at 6 h (3-fold, P < 0.05). The lipocalin 2 response was blocked by the GC-receptor antagonist RU-486 and was increased further by the protein synthesis blocker cycloheximide. Proliferation in lipocalin 2-overexpressing cells was less than in control cells (49%, P < 0.05), and overexpression caused an increase in collagen type X expression (4-fold, P < 0.05). The effects of lipocalin 2 overexpression on chondrocyte proliferation (64%, P < 0.05) and collagen type X expression (8-fold, P < 0.05) were further exacerbated with the addition of 10-6 M Dex. This synergistic effect may be explained by a further increase in lipocalin 2 expression with Dex treatment of transfected cells (45%, P < 0.05). These results suggest that lipocalin 2 may mediate Dex effects on chondrocytes and provides a potential novel mechanism for GC-induced growth retardation. [ABSTRACT FROM AUTHOR]

Longitudinal growth, which is primarily due to chondrocytic activity at the level of the epiphyseal growth plate, is influenced by many hormones and growth factors in an endocrine and paracrine manner. Their influence is even more complex during the accelerated growth period of puberty that accounts for about 20% of final adult height. Although abnormalities of growth during puberty are very common, the underlying mechanisms that govern the beginning and cessation of pubertal growth at the level of the growth plate are poorly understood. Sex steroids play a crucial role in pubertal growth both at the systemic level via the GH/IGF-1 axis and at the local level of the epiphyseal growth plate. In both sexes it is now accepted that oestrogen is the critical hormone in controlling growth plate acceleration and fusion. This paper reviews the mechanisms that influence pubertal growth and the problems that are associated with disorders of gonadal function. [ABSTRACT FROM AUTHOR]

The article focuses on consensus statement on management of intersex disorders in children in Great Britain. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology believe that it is timely to review the management of intersex or disorders of sexual development in children in the country.

Biodiesel is an alternative to fossil fuels for diesel engines, yet actual biofuel properties need to be tuned to comply with fuel standards. In particular, fuel stability is required for efficiency and commercial use. Fuel stability varies with the nature and proportion of chemical functional groups of biodiesel. Optimum oxidation stability is required because degradation by oxidation gives products that compromise fuel properties and impair fuel quality and engine performance. For instance, oxidation induces the formation of short-chain corrosive acids and deposits. Here, we review techniques to improve the oxidation stability of biodiesel. For instance, stability is improved by additives such as antioxidants. Factors influencing oxidation stability include composition of fatty acids, acid content, peroxide content, iodine content, viscosity, insoluble impurities, external conditions, and storage material. Antioxidants reduce lipid peroxidation at the beginning of the chain reaction and increase the onset temperatures. [ABSTRACT FROM AUTHOR]

This article investigates the dust ion acoustic multi-shock wave excitations in weakly relativistic multi-component plasma by assuming nonthermal, nonextensive electrons and positrons, relativistic ion fluid having kinetic viscosity and immobile dust. Burgers equation is derived to investigate such excitations by applying the reductive perturbation method. The exponential functions are directly implemented to determine the novel multi-shock wave solution of Burgers equation. The dust ion acoustic (DIA) multi-shock wave excitations are investigated systematically to reveal the effects of parameters, namely, viscosity coefficient of ions, positron to electron density ratio, immobile dust to electron density ratio, ion to electron temperature ratio, electron to positron temperature ratio, and relativistic streaming factor of ions in the presence of nonthermal, nonextensive, and concurrently acting nonthermal and nonextensive electrons as well as positrons. It is found that the amplitudes and widths of not only single, but also multi-shock wave compressive and rarefactive electrostatic potential structures are changed with the influence of all plasma parameters. The obtained results may be useful to analyze the nature of DIA multi-shock wave phenomena in various astrophysical as well as space environments (particularly, in pulsar relativistic winds with supernova ejecta) and future studies in plasma laboratory. [ABSTRACT FROM AUTHOR]

A mathematical framework has been designed to speculate the physical aspects of a binary chemical reaction (BCR) and Arrhenius activation energy (ACE) on magnetohydrodynamics Williamson micropolar nanofluid flow through a vertical stretching sheet. The fluid viscosity, electrical and thermal conductivity are presumed as reliant temperature function. Furthermore, the Lorentz force is deployed with an angle to the normal of the fluid flow. The natural transformations have been chosen to determine the non-dimensional regular expressions of the model. A conditionally stable finite difference analysis (explicit) is implemented to establish the computational analysis of the transfigured non-linear system of PDEs. The precision of the present numerical solution has been enriched by accomplishing analysis of stability as well as system convergence of finite difference analysis. The graphical representation, along with the tabular depiction, has been done for narrating the physical behaviour of important parameters extensively on various flow fields. The fluctuation of the boundary layer thickness is traced out with the assistance of streamlines, isotherms, and iso-concentration for the impression of the buoyancy ratio parameter and Lewis number. To draw perfection, achieved consequences of the current solution have been contrasted with some subsisting literature. [ABSTRACT FROM AUTHOR]

Childhood-onset growth hormone deficiency (CO-GHD) is an endocrine condition associated with a broad range of health issues from childhood through to adulthood, which requires particular attention during the transition period from adolescence to young adulthood. There is uncertainty in the clinical practice of the management of CO-GHD during transition regarding the clinical assessment and management of individual patients during and after transition to obtain optimal follow-up and improved health outcomes. Despite the availability of clinical guidelines providing the framework for transition of young adults with CO-GHD, there remains substantial variation in approaching transitional care among pediatric and adult services. A well-structured and coordinated transitional plan with clear communication and direct collaboration between pediatric and adult health care to ensure optimal management of adolescents with CO-GHD during transition is needed. [ABSTRACT FROM AUTHOR]

Study Question: What is the likelihood of identifying genetic or endocrine abnormalities in a group of boys with 46, XY who present to a specialist clinic with a suspected disorder of sex development (DSD)?Summary Answer: An endocrine abnormality of the gonadal axis may be present in a quarter of cases and copy number variants (CNVs) or single gene variants may be present in about half of the cases.What Is Known Already: Evaluation of 46, XY DSD requires a combination of endocrine and genetic tests but the prevalence of these abnormalities in a sufficiently large group of boys presenting to one specialist multidisciplinary service is unclear.Study, Design, Size, Duration: This study was a retrospective review of investigations performed on 122 boys.Participants/materials, Setting, Methods: All boys who attended the Glasgow DSD clinic, between 2010 and 2015 were included in the study. The median external masculinization score (EMS) of this group was 9 (range 1-11). Details of phenotype, endocrine and genetic investigations were obtained from case records.Main Results and the Role Of Chance: An endocrine abnormality of gonadal function was present in 28 (23%) with a median EMS of 8.3 (1-10.5) whilst the median EMS of boys with normal endocrine investigations was 9 (1.5-11) (P = 0.03). Endocrine abnormalities included a disorder of gonadal development in 19 (16%), LH deficiency in 5 (4%) and a disorder of androgen synthesis in 4 (3%) boys. Of 43 cases who had array-comparative genomic hybridization (array-CGH), CNVs were reported in 13 (30%) with a median EMS of 8.5 (1.5-11). Candidate gene analysis using a limited seven-gene panel in 64 boys identified variants in 9 (14%) with a median EMS of 8 (1-9). Of the 21 boys with a genetic abnormality, 11 (52%) had normal endocrine investigations.Limitations, Reasons For Caution: A selection bias for performing array-CGH in cases with multiple congenital malformations may have led to a high yield of CNVs. It is also possible that the yield of single gene variants may have been higher than reported if the investigators had used a more extended gene panel.Wider Implications Of the Findings: The lack of a clear association between the extent of under-masculinization and presence of endocrine and genetic abnormalities suggests a role for parallel endocrine and genetic investigations in cases of suspected XY DSD.Study Funding/competing Interest(s): RN was supported by the James Paterson Bursary and the Glasgow Children's Hospital Charity Summer Scholarship. SFA, RM and EST are supported by a Scottish Executive Health Department grant 74250/1 for the Scottish Genomes Partnership. EST is also supported by MRC/EPSRC Molecular Pathology Node and Wellcome Trust ISSF funding. There are no conflicts of interest.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether a short-term change in circulating androgens is associated with changes in the transcriptome of the peripheral blood mononuclear cells (PBMC). Aims and methods: To explore the effect of hCG stimulation on the PBMC transcriptome, 12 boys with a median age (range) of 0.7 years (0.3, 11.2) who received intramuscular hCG 1500u on 3 consecutive days as part of their investigations underwent transcriptomic array analysis on RNA extracted from peripheral blood mononuclear cells before and after hCG stimulation. Results: Median pre- and post-hCG testosterone for the overall group was 0.7 nmol/L (<0.5, 6) and 7.9 nmol/L (<0.5, 31.5), respectively. Of the 12 boys, 3 (25%) did not respond to hCG stimulation with a pre and post median serum testosterone of <0.5 nmol/L and <0.5 nmol/L, respectively. When corrected for gene expression changes in the nonresponders to exclude hCG effects, all 9 of the hCG responders consistently demonstrated a 20% or greater increase in the expression of piR-37153 and piR-39248, non-coding PIWI-interacting RNAs (piRNAs). In addition, of the 9 responders, 8, 6 and 4 demonstrated a 30, 40 and 50% rise, respectively, in a total of 2 further piRNAs. In addition, 3 of the responders showed a 50% or greater rise in the expression of another small RNA, SNORD5. On comparing fold-change in serum testosterone with fold-change in the above transcripts, a positive correlation was detected for SNORD5 (P = 0.01). Conclusions: The identification of a dynamic and androgen-responsive PBMC transcriptome extends the potential value of the hCG test for the assessment of androgen sufficiency. [ABSTRACT FROM AUTHOR]

Background: With the proliferation of rare disease registries, there is a need for registries to undergo an assessment of their quality against agreed standards to ensure their long-term sustainability and acceptability.This study was performed to evaluate the I-DSD and I-CAH Registries and identify their strengths and weaknesses.Methods: The design and operational aspects of the registries were evaluated against published quality indicators. Additional criteria included the level of activity, international acceptability of the registries and their use for research.Results: The design of the I-DSD and I-CAH Registries provides them with the ability to perform multiple studies and meet the standards for data elements, data sources and eligibility criteria. The registries follow the standards for data security, governance, ethical and legal issues, sustainability and communication of activities. The data have a high degree of validity, consistency and accuracy and the completeness is maximal for specific conditions such as androgen insensitivity syndrome and congenital adrenal hyperplasia. In terms of research output, the external validity is strong but the wide variety of cases needs further review. The internal validity of data was condition specific and highest for conditions such as congenital adrenal hyperplasia. The shift of the registry from a European registry to an international registry and the creation of a discrete but linked CAH registry increased the number of users and stakeholders as well as the international acceptability of both registries.Conclusions: The I-DSD and I-CAH registries comply with the standards set by expert organisations. Recent modifications in their operation have allowed the registries to increase their user acceptability. [ABSTRACT FROM AUTHOR]

Background: Adolescents with childhood onset growth hormone deficiency (CO-GHD) require re-evaluation of their growth hormone (GH) axis on attainment of final height to determine eligibility for adult GH therapy (rhGH). Aim: Retrospective multicentre review of management of young adults with CO-GHD in four paediatric centres in Scotland during transition. Patients: Medical records of 130 eligible CO-GHD adolescents (78 males), who attained final height between 2005 and 2013 were reviewed. Median (range) age at initial diagnosis of CO-GHD was 10.7 years (0.1-16.4) with a stimulated GH peak of 2.3 µg/l (0.1-6.5). Median age at initiation of rhGH was 10.8 years (0.4-17.0). Results: Of the 130 CO-GHD adolescents, 74/130(57%) had GH axis re-evaluation by stimulation tests /IGF-1 measurements. Of those, 61/74 (82%) remained GHD with 51/74 (69%) restarting adult rhGH. Predictors of persistent GHD included an organic hypothalamic-pituitary disorder and multiple pituitary hormone deficiencies (MPHD). Of the remaining 56/130 (43%) patients who were not re-tested, 34/56 (61%) were transferred to adult services on rhGH without biochemical retesting and 32/34 of these had MPHD. The proportion of adults who were offered rhGH without biochemical re-testing in the four centres ranged between 10 and 50% of their total cohort. Conclusions: A substantial proportion of adults with CO-GHD remain GHD, particularly those with MPHD and most opt for treatment with rhGH. Despite clinical guidelines, there is significant variation in the management of CO-GHD in young adulthood across Scotland. [ABSTRACT FROM AUTHOR]

Background: Hypercalcaemia is rare in children and may present with characteristic signs/symptoms or coincidentally following investigations for a variety of non-specific conditions. The aetiologies of childhood hypercalcaemia are diverse. Untreated sustained hypercalcaemia has serious clinical consequences. However there is limited data regarding the true frequency and aetiologies of childhood hypercalcaemia.Aim: To determine the frequency of severe childhood hypercalcaemia in routine clinical practice.Methods: The laboratory database was searched for all children (0-17 years) with severe hypercalcaemia defined as non-adjusted ≥2.90 mmol/L from 2007-2012. Hypercalcaemia was categorised as either transient (1 day) or sustained (≥2 consecutive days). Retrospective analysis of all cases of sustained severe hypercalcaemia was performed to identify the underlying aetiology.Results: Over the 5 year period, 206 children were identified as severely hypercalcaemic ≥2.90 mmol/L (0.3% all 61,380 calcium requests). Of these 131 (63.3%) children were classified as having sustained hypercalcaemia. The frequency of severe hypercalcaemia was highest in neonates (42% of sustained cases) and was inversely related to age. Sepsis was the most common aetiology (24%), particularly in neonates where it accounted for 41% of all causes of neonatal hypercalcaemia. Endocrine aetiologies included congenital adrenal hyperplasia (2 cases), fat necrosis (1), Addison's disease (2). A genetic cause was identified in 3 children (2 familial hypocalciuria hypercalcaemia, 1 Williams syndrome).Conclusions: Sustained hypercalcaemia affects 1 in 500 children in a general hospital setting. The frequency was highest in neonates and underlying aetiology differed markedly with age. All children with sustained hypercalcaemia require thorough investigation to determine the underlying aetiology to ensure appropriate management. [ABSTRACT FROM AUTHOR]

Presents a letter regarding direct assays for testosterone.

The suppressor of cytokine signalling (Socs2-/-)-knockout mouse is characterised by an overgrowth phenotype due to enhanced GH signalling. The objective of this study was to define the Socs2-/- bone phenotype and determine whether GH promotes bone mass via IGF1-dependent mechanisms. Despite no elevation in systemic IGF1 levels, increased body weight in 4-week-old Socs2-/- mice following GH treatment was associated with increased cortical bone area (Ct.Ar) (P<0.01). Furthermore, detailed bone analysis of male and female juvenile and adult Socs2-/- mice revealed an altered cortical and trabecular phenotype consistent with the known anabolic effects of GH. Indeed, male Socs2-/- mice had increased Ct.Ar (P<0.05) and thickness associated with increased strength. Despite this, there was no elevation in hepatic Igfl expression, suggesting that the anabolic bone phenotype was the result of increased local GH action. Mechanistic studies showed that in osteoblasts and bone of Socs2-/- mice, STAT5 phosphorylation was significantly increased in response to GH. Conversely, overexpression of SOCS2 decreased GH-induced STAT5 signalling. Although an increase in Igfl expression was observed in Socs2-/- osteoblasts following GH, it was not evident in vivo. Igfl expression levels were not elevated in response to GH in 4-week-old mice and no alterations in expression was observed in bone samples of 6-week-old Socs2-/- mice. These studies emphasise the critical role of SOCS2 in controlling the local GH anabolic bone effects. We provide compelling evidence implicating SOCS2 in the regulation of GH osteoblast signalling and ultimately bone accrual, which maybe via mechanisms that are independent of IGF1 production in vivo. [ABSTRACT FROM AUTHOR]

Objective Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro-architecture and bone marrow adiposity ( BMA) by MRI in adults with osteogenesis imperfecta ( OI) and endocrinopathy including GH deficiency and/or hypogonadism. Measurements High-resolution micro- MRI images were acquired at the tibia using 3T MRI to calculate parameters of bone micro-architecture in seven adults with OI and 10 adults with endocrinopathies. MR Spectroscopy was performed in participants to calculate vertebral BMA, which was expressed as percentage fat fraction (% FF). Lumbar spine DXA was performed to assess bone mineral density. The MRI data were compared with a group of 22 healthy adults who were divided into two age-matched control groups. Results Intra-operator repeatability was high, with an average CoV of 1% for micro- MRI and 2·5% for MRS. The ratio of apparent bone volume to total volume (app BV/ TV) in the endocrinopathy and OI groups was lower than in age-matched control groups ( P = 0·003 and P = 0·008 respectively). A weak association between DXA BMD and app BV/ TV was also observed ( r = 0·5, P = 0·045). % FF was higher in the endocrinopathy group than in the age-matched control group ( P = 0·005), but no difference in % FF was observed between the OI group and their age-matched control group ( P = 0·26). Conclusions MRI provides valuable detailed information on the micro-architecture and adiposity of bones and is capable of showing clear differences in bone parameters in a range of clinical conditions associated with abnormal bone health. [ABSTRACT FROM AUTHOR]

Background. Clinically isolated syndrome (CIS) is the first neurologic episode of multiple sclerosis (MS). Magnetic resonance imaging (MRI) and clinical features are used to predict risk of conversion to MS. Objectives. The aim of this prospective study is to evaluate predictors of conversion of CIS to McDonald MS. Method. 97 patients with CIS have been followed for 2 years. Age of onset, gender, initial clinical presentation, and MRI brain and spine were assessed. The 2010 revised McDonald criteria were applied. Results. Fifty-nine patients (60.8%) with CIS converted to McDonald MS after 10.1 + 4.2 months. Thirty-seven (38.1%) of the convertors satisfied the diagnostic criteria based on the radiological parameters, while 21.7% sustained their second clinical events. A multivariate regression analysis revealed that high number of lesions in MRI (P = 0.001) and earlier age of onset (P = 0.043) predicted the conversion of CIS to McDonald MS. Gender (P = 0.5) and initial clinical presentation (optic pathway (P = 0.4), supratentorial (P = 0.91), brain stem/ cerebellum (P = 0.97), and spinal (P = 0.76)) were not statistically significant. Conclusion. Age of onset and MRI parameters can be used as predictors of CIS conversion to McDonald MS. Application of the 2010 revised McDonald criteria allows an earlier MS diagnosis. [ABSTRACT FROM AUTHOR]