The role of the 5f valence orbitals of early actinides in chemical bonding.

One of the long standing debates in actinide chemistry is the level of localization and participation of the actinide 5f valence orbitals in covalent bonds across the actinide series. Here we illuminate the role of the 5f valence orbitals of uranium, neptunium and plutonium in chemical bonding using advanced spectroscopies: actinide M4,5 HR-XANES and 3d4f RIXS. Results reveal that the 5f orbitals are active in the chemical bonding for uranium and neptunium, shown by significant variations in the level of their localization evidenced in the spectra. In contrast, the 5f orbitals of plutonium appear localized and surprisingly insensitive to different bonding environments. We envisage that this report of using relative energy differences between the 5fδ/φ and 5fπ*/5fσ* orbitals as a qualitative measure of overlap-driven actinyl bond covalency will spark activity, and extend to numerous applications of RIXS and HR-XANES to gain new insights into the electronic structures of the actinide elements.

Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution.

Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution.

Surveillance during an era of rapidly changing poliovirus epidemiology in India: the role of one vs. two stool specimens in poliovirus detection, 2000-2010.

Since 2004, efforts to improve poliovirus detection have significantly increased the volume of specimen testing from acute flaccid paralysis (AFP) patients in India. One option to decrease collection and testing burden would be collecting only a single stool specimen instead of two. We investigated stool specimen sensitivity for poliovirus detection in India to estimate the contribution of the second specimen. We reviewed poliovirus isolation data for 303984 children aged <15 years with AFP during 2000-2010. Using maximum-likelihood estimation, we determined specimen sensitivity of each stool specimen, combined sensitivity of both specimens, and sensitivity added by the second specimen. Of 5184 AFP patients with poliovirus isolates, 382 (7.4%) were identified only by the second specimen. Sensitivity was 91.4% for the first specimen and 84.5% for the second specimen; the second specimen added 7.3% sensitivity, giving a combined sensitivity of 98.7%. Combined sensitivity declined, and added sensitivity increased, as the time from paralysis onset to stool collection increased (P = 0.032). The sensitivity added by the second specimen is important to detect the last chains of poliovirus transmission and to achieve certification of polio eradication. For sensitive surveillance, two stool specimens should continue to be collected from each AFP patient in India.

Abdominal obesity and the spectrum of global cardiometabolic risks in US adults.

OBJECTIVE: To compare the association of obesity and abdominal obesity with cardiometabolic risk factor burden and global estimated coronary heart disease (CHD) risk among multiethnic US adults. DESIGN: Cross-sectional, survey study. SUBJECTS: A total of 4456 participants (representing 194.9 million adults) aged 20-79 years in the 2003-2004 National Health and Nutrition Examination Survey (NHANES). MEASUREMENTS: Body mass index (BMI) and waist circumference (WC) measures, CHD risk factors and a 10-year estimated CHD risk based on Framingham algorithms. Obesity was defined as a BMI >or=30 kg/m(2) and abdominal obesity as a WC >88 cm in women and >102 cm in men. High CHD risk status included diabetes, cardiovascular disease (CVD) or a 10-year Framingham risk score of >20%. RESULTS: Overall, abdominal obesity was present in 42.3% of men and 62.5% of women and in 53.6% of whites, 56.9% of blacks and 50.5% of Hispanics (P<0.001 between gender and ethnicity). However, using International Diabetes Federation (IDF)-recommended WC cut points for Hispanics, the prevalence of abdominal obesity was 78.3%. Mean levels of low-density lipoprotein cholesterol (LDL-C), systolic and diastolic blood pressure, fasting glucose and C-reactive protein increased, and high-density lipoprotein cholesterol (HDL-C) decreased (P<0.001) according to BMI and WC categories, although these associations were attenuated in blacks for blood pressure, LDL-C, HDL-C and triglycerides. Of those with high WC, 25-35% had >or=3 cardiometabolic risk factors. High CHD risk among those with high WC was most common in men (27.9%) and non-Hispanic whites (23.9%). Persons with a high vs normal WC, adjusted for age, gender, ethnicity and BMI were more likely to have >or=3 cardiometabolic risk factors (odds ratio (OR)=5.1, 95% confidence interval (CI)=3.9-6.6) and were classified as high CHD risk (OR=1.5, 95% CI=1.1-2.0). CONCLUSION: The association of abdominal obesity with risk factors varies by ethnicity and is independently associated with high CHD risk status, further validating its clinical significance.

Providing monovalent oral polio vaccine type 1 to newborns: findings from a pilot birth-dose project in Moradabad district, India.

PROBLEM: Poliovirus transmission remained a public health challenge in western Uttar Pradesh, India in late 2005 and early 2006. In 2006, the India Expert Advisory Group for Polio Eradication concluded that, given the peak incidence of polio among children 6 to 12 months of age, a targeted birth dose of oral polio vaccine may be necessary to interrupt intense poliovirus transmission in high risk areas. APPROACH: The Government of Uttar Pradesh, the National Polio Surveillance Project and the United Nations Children's Fund (UNICEF) implemented a pilot birth-dose project aimed at identifying and vaccinating all newborns with a dose of oral polio vaccine within 72 hours of birth in an effort to evaluate operational feasibility and potential impact on population immunity. LOCAL SETTING: The project was piloted in Moradabad district: zone 7 in Moradabad City (urban setting), Kunderki block (rural setting) and in select birthing hospitals. RELEVANT CHANGES: Between July 2006 and February 2007, 9740 newborns were identified, of which 6369 (65%) were vaccinated by project personnel within 72 hours of birth. Project coverage (for total newborns vaccinated) ranged from 39% (in zone 7) to 76% (in Kunderki block) of the estimated number of newborns vaccinated during previous supplemental immunization activities. LESSONS LEARNED: Birth-dose coverage among newborns was lower than expected. Expansion costs were estimated to be high, with marginal impact. The project, however, provided opportunities to strengthen newborn tracking systems which have increased the number of newborns and young infants vaccinated during supplemental immunization activities and enrolled in routine programmes.

Indirect costs of obesity: a review of the current literature.

This study reviews the recent literature on the relationship between obesity and indirect (non-medical) costs. Medline and Web of Science searches were conducted to identify published studies from 1992 to present that report indirect costs by obesity status; 31 studies were included. The indirect costs were grouped into six categories: costs associated with absenteeism, disability, premature mortality, presenteeism, workers' compensation, and total indirect costs. Compared with non-obese workers, obese workers miss more workdays due to illness, injury, or disability. Costs of premature mortality vary substantially across countries. The results for presenteeism and workers' compensation were mixed. More research is needed to determine obesity's causal role in increasing indirect costs, especially for workers' compensation and presenteeism. Cohort and longitudinal study designs should be a priority.

Evidence of a common founder for SCA12 in the Indian population.

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for approximately 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.

Novel reduced benzo[j]fluranthen-3-ones from Cladosporium cf. cladosporioides with cytokine production and tyrosine kinase inhibitory properties.

A series of reduced benzo[j]fluoranthen-3-ones (1-4) was isolated from fermentations of a fungal strain CBUK20700 (CBS 100220), classified as Cladosporium cf. cladosporioides, during a microbial extract screening programme to identify inhibitors of anti-CD28-induced interleukin-2 (IL-2) production by Jurkat E6-1 cells as potential immunosuppressive agents. These compounds were also found to be tyrosine kinase inhibitors. The structures of compounds 1-4 were elucidated by spectroscopic methods including the HMQC, HMBC and NOESY NMR experiments. The most potent compound in the series, (6bS,7R,8S)-7-methoxy-4,8,9-trihydroxy-1,6b,7,8-tetrahydro-2H-benzo[j]fluoranthen-3-one (1) inhibited anti-CD28-induced IL-2 production and Abl tyrosine kinase with IC50 values of 400 and 60 nM respectively. The 6b-stereoisomeric 2 was a moderate inhibitor of both IL-2 production and Abl tyrosine kinase while the 8-oxo derivative 3 was inactive in both assays. The 8-O-methyl ether 4 was a moderate inhibitor of IL-2 production but exhibited potent inhibition of Abl tyrosine kinase with an IC50 of 45 nM.

International perspectives: the profession of dietetics.

A survey about the professional characteristics of dietetics practice was mailed to 109 countries and representatives from 61 countries responded. Using the Human Development Index (HDI), a measure that reflects the life expectancy, education, and income of the population of each nation, countries were categorized as high, medium, or low HDI. This allowed comparisons among the HDI scores in the areas of education, professional practice, education, and practice competencies. Responding countries were 36.1% high HDI, 49.2% middle HDI, 8.2% low HDI, and 6.6% were unclassified. Dietetics was a nationally recognized profession in 81% of countries, with most having a professional association that represented dietitians. Clinical dietetics was the most frequently selected area of practice, followed by food service. Undergraduate academic programs in dietetics were available in 79% of countries and 49% offered graduate degrees. Most respondents rated competencies in clinical and community nutrition, along with competencies in professional practice, as important to their work. The results of this study can serve as a baseline as the profession evolves. Leaders in the dietetics profession can use these results to identify areas that need improvement. Collaboration with the United Nations family and sources that fund global initiatives can help in providing resources for the advancement of the profession. When the effectiveness of dietitians is improved, favorable changes in nutritional well-being on the global level can be expected.

Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission - long-term follow-up.

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Determinants of youth tobacco use in West Virginia: a comparison of smoking and smokeless tobacco use.

PURPOSE: To identify and compare the determinants of different types of tobacco use among rural youths and discuss the implication of these differences for youth tobacco use cessation. METHODS: Ninth grade participants (n = 883) were 95% white, between 13 and 19 years old with a mean age of 14.6 years. Students were classified into four exclusive groups: non-tobacco use, smoking only, smokeless tobacco (ST) use only, and conjoint smoking and ST use. The influences of 14 specific risk factors on tobacco use were investigated for each group using separate multiple logistic regression analyses. RESULTS: Among participants, 20% were smokers only, 6% were ST users only, and 10% were conjoint users. Students who had more friends (odds ratio [OR] =] 2.75) and siblings (OR = 1.96) who smoke, family problems (OR = 1.70), and favorable attitudes toward tobacco use (OR = 1.12) were more likely to smoke than were other students. Among students who used only ST, gender was a primary determinant (95% were male). Excluding gender, sibling ST use (OR = 4.28), friends' ST use (OR = 1.71), and favorable attitudes (OR = 1.11) were the most significant risk factors. Male students were also more likely to use both cigarettes and ST (OR = 8.62). In addition, among students who used both tobacco products, siblings' and friends' ST use were significant (OR = 3.09 and 2.13, respectively), as well as family problems (OR = 2.41) and attitude (OR = 1.15). Unlike smokers only or ST users only, lack of knowledge about tobacco was a significant determinant among conjoint users (OR = 1.39). CONCLUSIONS: Findings revealed that 7 of 14 factors were significant predictors of tobacco use. Some factors predicted smoking only, ST only, and conjoint use; however, the pattern of predictors varied for these three categories. Implications for these findings as they relate to tobacco use interventions are discussed.

A novel (6S)-4,6-dimethyldodeca-2E,4E-dienoyl ester of phomalactone and related alpha-pyrone esters from a Phomopsis sp. with cytokine production inhibitory activity.

A series of novel 6-substituted 5,6-dihydro-5-hydroxy-alpha-pyrone esters, 1 approximately 3, isolated from fermentations of a Phomopsis sp. (Xenova culture collection no. X22502) have been identified as inhibitors of lipopolysaccharide (LPS)-induced cytokine production. These include the (6S)-4,6-dimethyldodecadien-2E,4E-dienoyl ester of phomalactone, 1, and two analogues bearing a prop-2E-enoic acid moiety at the 6-position of the alpha-pyrone ring. (6S)-4,6-Dimethyl-2E,4E-dienoic acid, 4, and a hydroxylated analogue, 5, were also isolated and characterised. The most potent cytokine production inhibitor was 1, which inhibited LPS-induced tumour necrosis factor alpha (TNFalpha) production by U937 cells and LPS-induced interleukin 1beta (IL-1beta) production by peripheral blood mononuclear cells (PBMC) with IC50 values of 80 nM and 190 nM respectively. The effect of 1 in PBMC was selective for IL-1beta relative to TNFalpha. The inhibition of IL-1beta production by 1 involved a post-translational mechanism of action at the level of IL-1beta secretion as demonstrated by the lack of an effect on cell-associated IL-1beta production. 1 showed no effect on the activity of caspase 1 in cytosolic extracts from the THP1 monocytic cell line.

Legionella as a lower respiratory pathogen in north India.

One hundred patients of lower respiratory tract infection (LRTI) were prospectively studied over 2 years to find out if Legionella is a causative agent in these patients. In addition, 50 environmental samples and 50 age and sex matched controls were studied. Culture and direct fluorescent antibody testing (DFA) of respiratory tract secretions, and serodiagnosis by indirect immunofluorescence (IIF) and ELISA, were employed to detect Legionella. Respiratory tract secretions from all patients were negative for Legionella on culture and DFA. Low antibody titters to Legionella were observed in 21 patients and these could be attributed to cross reaction with other gram-negative bacteria. All environmental samples and controls tested negative for Legionella. Legionella does not seem to be an important lower respiratory tract pathogen in this part of the country and empirical addition of erythromycin to treatment regimens for pneumonia is not warranted in our setting.

Oral lichen planus update: clinical characteristics, treatment responses, and malignant transformation.

PURPOSE: To assess the current profile and the natural disease history of patients with oral lichen planus (OLP) and evaluate their responses to treatment. MATERIALS AND METHODS: Ninety-five community-referred patients with OLP, who were examined in our Oral Medicine Clinic between May 1995 and August 1996, comprised the study group. RESULTS: The OLP patients had been followed for 1-20 years (mean 6.1). The average age at first-recognized onset was 59 years, and there was a 2.3 to 1 female predominance. Only five of the patients knew of a family history of lichen planus. There were no evident associations with smoking, candida, systemic disease or medications. Of the 222 involved mucosal sites, the buccal mucosa was involved most often (79%) and the erosive form was most frequent. Of 70 patients who received systemic and/or topical corticosteroid treatment for pain (83%) or annoying irritation (17%), all but five obtained complete or satisfactory relief. A squamous cell carcinoma developed at a lesion site in three patients (3.2%) during the observation period.

Efficacy of combination therapy with insulin and oral hypoglycemic agents in patients with type II diabetes during a 1-year period.

In this retrospective study, the authors assess the efficacy of combined insulin and oral hypoglycemic agents (OHAs) in controlling glycemic levels, as well as lipid levels and insulin requirements, in 48 patients with type II diabetes mellitus during a 1-year period. Thirty-two of these patients had secondary failure to an OHA (group 1). Sixteen patients (group 2) were taking high doses of insulin alone. Overall, 64.6% of all the patients responded to the combination therapy and insulin at 6 months. Response was defined as a decrease in hemoglobin A1c of more than 0.5%. At 12 months, 50% of these patients continued to respond to this regimen. No significant differences were seen in the patients' total cholesterol and triglyceride levels between responders and nonresponders in each group. After 1 year of combination OHA and insulin therapy, 50% of the patients showed a 21.4% reduction in their daily insulin dose.

Three-dimensional image reconstruction using interferometric data from a limited field of view with noise.

A reconstruction of phase objects using an algebraic reconstruction technique in an unconfined environment from multidirectional interferometric data is presented. The effect of noise on the data from the interference patterns is studied. It is shown that in the presence of noise the number of iterations need to be critically evaluated; otherwise the solution tends to diverge. Criteria used to quantify the noise are presented. Also shown is a relationship between noise and the required number of iterations, which yields the least error in reconstruction. This procedure is applied to experimentally obtained interferometric data.

A nutrition/health training program for Peace Corps volunteers.

Nutrition and health education is a crucial component of the overall mission of the Peace Corps program. Individuals selected to work as Peace Corps volunteers need to be well prepared to perform this complex and challenging job in recipient countries. This article presents a model for a training program for Peace Corps trainees that was conducted over a 5-week period. The program was planned in accordance with some specific training guidelines that were provided by the Peace Corps. The trainees included nine women ranging in age from 22 to 61 years with diverse backgrounds; however, all had a BA/BS in a health-related discipline. Training curriculum included fundamental nutrition and health-related areas: basic nutrition, foods, clinical nutrition, maternal and child health, communicable diseases and sanitation, health strategies, and community development. Fifty percent of the curriculum was devoted to "hands-on" practical and clinical activities. Maternal and child health was emphasized in the training curriculum as this is an area of concern in all developing countries. The trainees were evaluated by weekly quizzes as well as completion of a special project involving applications of all their newly acquired skills. Implications of the training program are discussed.