Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis

Objective. IVIG is known to confer significant benefit in rheumatologic conditions, including inflammatory myopathy. This study aimed to assess the efficacy of IVIG across different aspects of internal organ involvement in refractory active SSc, particularly the gastrointestinal (GI) system. / Methods. SSc patients with overlap polymyositis who remained active and unresponsive to conventional disease-modifying agents and who subsequently received IVIG were identified. GI symptoms were assessed using validated questionnaires. The Medical Research Council Sum Score for muscle strength and modified Rodnan skin score (mRSS) were assessed. Serial measurements were undertaken at baseline prior to the first IVIG treatment and post-treatment in the most recent assessment. / Results. Fifteen SSc patients were consecutively recruited into this observational study. The mean duration of IVIG treatment was 2.3 years, with treatment frequency ranging from every 6 weeks to 4 months. Compared with baseline, there was a significant reduction in gastro-oesophageal reflux frequency and intensity mean scores (P = 0.006 and P = 0.013, respectively). Significant improvement in the Gastrointestinal Tract (GIT) 2.0 score from a baseline mean score of 1.07 (s.d. 0.67) to 0.60 (0.46) (P = 0.002) was observed. There was regression in the markers of muscle disease with a reduction in the mean (s.d.) Medical Research Council sum score and the median creatine kinase level (P = 0.001 and P = 0.025, respectively). Significant amelioration of the mean basal modified Rodnan skin score from 21.5 (s.d. 13.8) to 10 (10.6) (P = 0.005) was observed. / Conclusion. IVIG may be a helpful adjunctive therapy in the amelioration of some key clinical aspects in refractory SSc. Sustained benefit from IVIG suggests a specific immunomodulatory effect on those with established SSc GI complications

Some mixed Hodge structure on l^2-cohomology of covering of K\"ahler manifolds

We give methods to compute l^2-cohomology groups of a covering manifolds obtained by removing pullback of a (normal crossing) divisor to a covering of a compact K\"ahler manifold. We prove that in suitable quotient categories, these groups admit natural mixed Hodge structure whose graded pieces are given by expected Gysin maps.Comment: 40 pages. This revised version will be published in Mathematische Annale

An integrated biostratigraphy and seismic stratigraphy for the late Neogene continental margin succession in northern Taranaki Basin, New Zealand

Our aim has been to develop an integrated biostratigraphy and seismic stratigraphy for the Pliocene and Pleistocene formations (Ariki, Mangaa, Giant Foresets) in northern Taranaki Basin to better understand the evolution of the modern continental margin offshore central-western North Island, New Zealand. Detailed mapping of seismic reflectors in part of the basin, when compared with correlations of late Neogene stage boundaries between 11 well sections, has highlighted crossover between the datasets. To help resolve this issue, the biostratigraphy of the Pliocene-Pleistocene parts of each of four well sections (Arawa-1, Ariki-1, Kora-1, and Wainui-1) has been re-examined using a dense suite of samples. In addition, the biostratigraphy of seven other well sections (Awatea-1, Kahawai-1, Mangaa-1, Taimana-1, Tangaroa-1, Te Kumi-1, and Turi-1) has been re-evaluated. The crossover is partly attributed to a combination of sampling resolution inherent in exploration well sections, the mixed nature of cuttings samples, and the general scarcity of age-diagnostic planktic foraminifera in the late Neogene formations. The achievement of seismic closure suggests that error in the mapping of the seismic reflectors is not a significant source of the uncertainty (crossover). We have developed a workable time-stratigraphic framework by qualitatively weighting the biostratigraphic data in each of the well sections, thereby identifying the parts of particular well sections with the highest resolution microfossil data and the optimal stratigraphic position of stage boundaries with respect to the mapped seismic horizons/seismic units. Hence, it is possible to assign the known numerical ages for these stage boundaries to reflection horizons/seismic units mapped within the basin. We have applied this information to produce a series of isopach maps for successive stage boundaries that help show the sedimentary evolution of the continental margin succession west of central North Island

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Tomato protoplast DNA transformation: physical linkage and recombination of exogenous DNA sequences

Tomato protoplasts have been transformed with plasmid DNA's, containing a chimeric kanamycin resistance gene and putative tomato origins of replication. A calcium phosphate-DNA mediated transformation procedure was employed in combination with either polyethylene glycol or polyvinyl alcohol. There were no indications that the tomato DNA inserts conferred autonomous replication on the plasmids. Instead, Southern blot hybridization analysis of seven kanamycin resistant calli revealed the presence of at least one kanamycin resistance locus per transformant integrated in the tomato nuclear DNA. Generally one to three truncated plasmid copies were found integrated into the tomato nuclear DNA, often physically linked to each other. For one transformant we have been able to use the bacterial ampicillin resistance marker of the vector plasmid pUC9 to 'rescue' a recombinant plasmid from the tomato genome. Analysis of the foreign sequences included in the rescued plasmid showed that integration had occurred in a non-repetitive DNA region. Calf-thymus DNA, used as a carrier in transformation procedure, was found to be covalently linked to plasmid DNA sequences in the genomic DNA of one transformant. A model is presented describing the fate of exogenously added DNA during the transformation of a plant cell. The results are discussed in reference to the possibility of isolating DNA sequences responsible for autonomous replication in tomato.

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

Animistic pragmatism and native ways of knowing: adaptive strategies for overcoming the struggle for food in the sub-Arctic

Background. Subsistence norms are part of the “ecosophy” or ecological philosophy of Alaska Native Peoples in the sub-Arctic, such as the Inupiat of Seward Peninsula. This kind of animistic pragmatism is a special source of practical wisdom that spans over thousands of years and which has been instrumental in the Iñupiat’s struggle to survive and thrive in harsh and evolving environments. Objective. I hope to show how narrative in relationship to the “ecosophy” of Alaska Native peoples can help to promote a more ecological orientation to address food insecurity in rural communities in Alaska. Alaska Native ecosophy recommends central values and virtues necessary to help address concerns in Alaska’s rural communities. Design. Here, I will tease out the nature of this “ecosophy” in terms of animistic pragmatism and then show why this form of pragmatism can be instrumental for problematizing multi-scalar, intergenerational, uncertain and complex environmental challenges like food security. Results. Native elders have been the embodiment of trans-generational distributed cognition,1 for example, collective memory, norms, information, knowledge, technical skills and experimental adaptive strategies. They are human “supercomputers,” historical epistemologists and moral philosophers of a sort who use narrative, a form of moral testimony, to help their communities face challenges and seize opportunities in the wake of an ever-changing landscape. Conclusions. The “ecosophy” of the Iñupiat of Seward Peninsula offers examples of “focal practices”, which are essential for environmental education. These focal practices instil key virtues, namely humility, gratitude, self-reliance, attentiveness, responsibility and responsiveness, that are necessary for subsistence living

Adult mortality of diseases and injuries attributable to selected metabolic, lifestyle, environmental, and infectious risk factors in Taiwan: A comparative risk assessment

Background: To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. Methods: We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. Results: In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850-17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330-16,450), high blood pressure (11,190 deaths, 95% UI: 8,190-14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370-9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970-9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040-9,190), and 7,400 deaths (95% UI: 6,670-8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220-13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610-6,980) and 3,170 deaths (95% UI: 1,860-4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190-2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. Conclusions: High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition