Bone mineral content after renal transplantation

Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased signifiantly (p<0.05) but marginally in placebo-treated patients (n=14) (initial BMC 1.09±0.25 g/cm; final BMC 1.05±0.24). Fourteen patients were prophylactically given 1,25(OH)2vitamin D3 in a dose which avoided hypercalcemia and hypercalciuria (sim0.25 µg/day); under 1,25(OH)2 vitamin D3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94±0.21 g/cm; final BMC 0.95±0.21), but the difference between placebo and 1,25(OH)2 vitamin D3 narrowly missed statistical significance (p=0.066). It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)2 vitamin D3 to slightly ameliorate forearm (cortical) BMC loss

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors

Boundaries and Crossings: Religious Fluidity in Twenty-first Century India

Following Partition, newly independent India adopted a constitution based on secularism and rights for minorities. In recent years, under the Bharatiya Janata Party government, this model of society has been steadily eroded and supplanted by one favouring Hindu nationalism. This shift has changed the ways in which various religious communities relate to each other as well as their relationship with the state. In this special issue, we examine how these social and political shifts have impacted on the willingness of individuals to engage across religious boundaries and highlight instances of continuing religious cosmopolitanism

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

Anticipatory governance for social-ecological resilience

Anticipation is increasingly central to urgent contemporary debates, from climate change to the global economic crisis. Anticipatory practices are coming to the forefront of political, organizational, and citizens’ society. Research into anticipation, however, has not kept pace with public demand for insights into anticipatory practices, their risks and uses. Where research exists, it is deeply fragmented. This paper seeks to identify how anticipation is defined and understood in the literature and to explore the role of anticipatory practice to address individual, social, and global challenges. We use a resilience lens to examine these questions. We illustrate how varying forms of anticipatory governance are enhanced by multi-scale regional networks and technologies and by the agency of individuals, drawing from an empirical case study on regional water governance of Malaren, Sweden. Finally, we discuss how an anticipatory approach can inform adaptive institutions, decision making, strategy formation, and societal resilience

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighborhood perceptions : The Whitehall II cohort study

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighbourhood perceptions: The Whitehall II cohort study Gill Mein (corresponding author), Robert Grant. Faculty of Health, Social Care and Education. Kingston University and St George’s University of London Background: To explore associations between pets, and specifically dog ownership and sleep, health, exercise and neighbourhood. Methods: Cross sectional examination of 6575 participants of the Whitehall II study aged between 59-79 years. We used self-assessed measurement scales of the Short Form (SF36), General Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep, exercise, and perceptions of local neighbourhood. In addition the Mini Mental State Examination which is administered to test global cognitive status (MMSE) Results: We found 2/7 people owned a pet and of those 64% were “very” attached to their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR 16.8 to 38.7), p=0.0001), and in dog owners than other pets (median 32.3 (IQR 20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p<0.0001). Moderate exercise was also significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to 21.9) vs 9.8 (IQR 2.8 to 19.5), p<0.0001), and dog owners than owners of other pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p=0.0002) but there were no significant differences with vigorous exercise. We found that pet owners were significantly more positive about their neighbourhood than non-owners on 8/9 questions, while dog owners were (significantly) even more positive than owners of other pets on 8/9 questions. Associations with sleep were mixed, although dog owners had less trouble falling asleep than non-dog owners, with borderline statistical significance. Conclusion: Dog owners feel more positive about their neighbourhood, do more exercise, and fall asleep more easily than non-dog owners. These results suggest that dog owners could be more likely to exercise by walking their dogs and therefore may be more familiar and positive about the area in which they walk their dog

Implementing the SCCM Family-Centered Care Guidelines in Critical Care Nursing Practice

Family-centered care is an important component of holistic nursing practice, particularly in critical care, where the impact on families of admitted patients can be physiologically and psychologically burdensome. Family-centered care guidelines, developed by an international group of nursing, medical, and academic experts for the American College of Critical Care Medicine/Society of Critical Care Medicine, explore the evidence base in 5 key areas of family-centered care. Evidence in each of the guideline areas is outlined and recommendations are made about how critical care nurses can use this information in family-centered care practice.</jats:p

The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas

The transcription factor Pax6 is a developmental regulator with a crucial role in development of the eye, brain, and olfactory system. Pax6 is also required for correct development of the endocrine pancreas and specification of hormone producing endocrine cell types. Glucagon-producing cells are almost completely lost in Pax6-null embryos, and insulin-expressing beta and somatostatin-expressing delta cells are reduced. While the developmental role of Pax6 is well-established, investigation of a further role for Pax6 in the maintenance of adult pancreatic function is normally precluded due to neonatal lethality of Pax6-null mice. Here a tamoxifen-inducible ubiquitous Cre transgene was used to inactivate Pax6 at 6 months of age in a conditional mouse model to assess the effect of losing Pax6 function in adulthood. The effect on glucose homeostasis and the expression of key islet cell markers was measured. Homozygous Pax6 deletion mice, but not controls, presented with all the symptoms of classical diabetes leading to severe weight loss requiring termination of the experiment five weeks after first tamoxifen administration. Immunohistochemical analysis of the pancreata revealed almost complete loss of Pax6 and much reduced expression of insulin, glucagon, and somatostatin. Several other markers of islet cell function were also affected. Notably, strong upregulation in the number of ghrelin-expressing endocrine cells was observed. These findings demonstrate that Pax6 is essential for adult maintenance of glucose homeostasis and function of the endocrine pancreas

The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts

Nonsyndromic orofacial clefts (OFC) are common birth defects caused by certain genes interacting with environmental factors. Mutations and association studies indicate that the homeobox gene MSX1 plays a role in human clefting. In a Dutch case-control triad study (mother, father, and child), we investigated interactions between MSX1 and the parents' periconceptional lifestyle in relation to the risk of OFC in their offspring. We s