Growth of collisional orogens from small and cold to large and hot - inferences from geodynamic models

It is well documented that the interplay between crustal thickening and surface processes determines growth of continent‐continent collision orogens from small and cold to large and hot. Additionally, studies have demonstrated that the structural style of a mountain belt is strongly influenced by inherited (extensional) structures, the pattern of erosion and deposition, as well as the distribution of shallow detachment horizons. However, the factors controlling distribution of shortening and variable structural style as a function of convergence and surface process efficiency remain less explored. We use a 2D upper‐mantle scale plane‐strain thermo‐mechanical model (FANTOM) coupled to a planform, mass conserving surface‐process model (Fastscape), to investigate the long‐term evolution of mountain belts and the influence of lithospheric pull, extensional inheritance, surface processes efficiency, and decoupling between thin‐and thick‐skinned tectonics. We establish an evolutionary shortening distribution for orogenic growth from a mono‐vergent wedge to an orogenic plateau, and find that internal crustal loading is the main factor controlling the large scale evolution, while lithospheric pull modulates the plate driving force for orogenesis. Limited foreland‐basin filling and minor exhumation of the orogen core are characteristic for low surface‐process efficiency, while thick foreland‐basin fill, and profound exhumation of the orogen core are characteristic for high surface‐process efficiency. Utilizing a force balance analysis, we show how inherited structures, surface processes, and decoupling between thin‐and thick‐skinned deformation influence structural style during orogenic growth. Finally, we present a comparison of our generic modeling results with natural systems, with a particular focus on the Pyrenees, Alps, and Himalaya‐Tibet

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Anthropometric Variables Accurately Predict Dual Energy X-Ray Absorptiometric-Derived Body Composition and Can Be Used to Screen for Diabetes

The current world-wide epidemic of obesity has stimulated interest in developing simple screening methods to identify individuals with undiagnosed diabetes mellitus type 2 (DM2) or metabolic syndrome (MS). Prior work utilizing body composition obtained by sophisticated technology has shown that the ratio of abdominal fat to total fat is a good predictor for DM2 or MS. The goals of this study were to determine how well simple anthropometric variables predict the fat mass distribution as determined by dual energy x-ray absorptometry (DXA), and whether these are useful to screen for DM2 or MS within a population. To accomplish this, the body composition of 341 females spanning a wide range of body mass indices and with a 23% prevalence of DM2 and MS was determined using DXA. Stepwise linear regression models incorporating age, weight, height, waistline, and hipline predicted DXA body composition (i.e., fat mass, trunk fat, fat free mass, and total mass) with good accuracy. Using body composition as independent variables, nominal logistic regression was then performed to estimate the probability of DM2. The results show good discrimination with the receiver operating characteristic (ROC) having an area under the curve (AUC) of 0.78. The anthropometrically-derived body composition equations derived from the full DXA study group were then applied to a group of 1153 female patients selected from a general endocrinology practice. Similar to the smaller study group, the ROC from logistical regression using body composition had an AUC of 0.81 for the detection of DM2. These results are superior to screening based on questionnaires and compare favorably with published data derived from invasive testing, e.g., hemoglobin A1c. This anthropometric approach offers promise for the development of simple, inexpensive, non-invasive screening to identify individuals with metabolic dysfunction within large populations

Anterior fundoplication at the time of congenital diaphragmatic hernia repair

The loss of normal anatomic barriers in neonates with congenital diaphragmatic hernia (CDH) can predispose children to gastroesophageal reflux (GER). In an attempt to improve post-operative feeding, we have added a modified anterior fundoplication to restore natural gastric and esophageal positioning. The institutional review board of both participating centers approved this study. Between 1997 and 2008, 13 neonates with high-risk anatomy underwent repair of CDH combined with an anterior fundoplication (Boix-Ochoa). The anatomic indications for concomitant fundoplication were absence of an intra-abdominal esophagus, an obtuse angle of His, and a small, vertically oriented stomach. Ten patients survived to discharge and eight were on full oral nourishment. One required partial gastrostomy feedings for an improving oral aversion and quickly progressed to full oral feedings. One patient with chromosomal anomalies and swallowing dysfunction remained on long-term bolus gastrostomy feedings. Two with progressive symptoms of GER and failure to thrive required conversion to a 360° wrap after 18 months of medical management. This was performed in conjunction with a planned, staged muscle flap reconstruction in one patient. There were no complications related to the fundoplication. Anatomic predictors of severe GER can be efficiently countered at the time of CDH repair. A modified fundoplication should be considered in the operative management of high-risk infants

The interphase chromatin special state zones

The possibility is demonstrated of RecA protein of E. coli introduction into eukaryotic cell with preservation of its biologicall activity. The character of this protein affinity to chromatin of different degree of condensation is shown on cytological level (undirect immunofluorescent method combined with cytophotometry) for different stages of cellular cycle (protein is not tested in meta- and anaphase chromosomes). The presence of bacterial RecA protein in the nuclei and cytoplasm of cells both in vitro and in vivo is confirmed with the help of immunoelectron microscopy. Studies were carried out on cultures of HeLa and Ltk⁻ cells and also in vivo on hepatocytes after direct injection on RecA protein and plasmid pKCR2 enclosed in liposomes into the liver of adult mice line BALB/c. Proceeding from the experimental data obtained and also considering the fact that RecA protein mainly connects with single-stranded DNA, the assumption is done about existence of special state chromatin zones (SSCZ). For these zones the active affinity to RecA protein serum is character with intensive fluorescence, thus they may correspond to some actively expressing genes, gathered in clusters.Показано можливість введення до еукаріотичної клітини RecA-білка Е. coli із збереженням його біологічної активності. На цитологічному рівні (непрямий імунофлюоресцентний метод з цитофотометрією) визначено характер зв'язування RecA- білка з хроматином різного ступеню спіралізації на окремих стадіях клітинного циклу (у мета- і анафазних хромосомах білок не тестується). Присутність бактеріального білка у цитоплазмі і ядрах клітин in vivo та in vitro підтверджена також імуноелектронною мікроскопією. Виходячи з отриманих експериментальних даних та враховуючи переважне зв'язування RecA-білка з онДНК, зроблено припущення про існування зон особливого стану хроматина (ЗOCX), які характеризуються активним зв'язуванням з сироваткою до бактеріального RecA-білка та інтенсивною флюоресценцією і можуть відповідати зібраним у кластери активно експресуючим генам. Експерименти виконано на культурах клітин HeLa і Ltk⁻, а також in vivo на гепатоцитах після прямого введення білка та плазміди pKCR2 у складі ліпосом до печінки дорослих мишей лінії BALB/c.Показана возможность введения в эукариотическую клетку RecA - белка Е. coli с сохранением его биологической активности . На цитологическом уровне (непрямой иммунофлюоресцентный метод с цитофотометрии ) определен характер связывания RecA - белка с хроматином разной степени спирализации на отдельных стадиях клеточного цикла (в мета- и анафазного хромосомах белок не тестируется ) . Присутствие бактериального белка в цитоплазме и ядрах клеток in vivo и in vitro подтверждено также имуноэлектронной микроскопией . Исходя из полученных экспериментальных данных и учитывая преимущественное связывание RecA - белка с онДНК , высказано предположение о существовании зон особого состояния хроматина ( ЗOCX ) , которые характеризуются активным связыванием с сывороткой к бактериальному RecA - белка и интенсивной флюоресценцией и могут соответствовать собранным в кластеры активно экспрессирующим генам . Эксперименты выполнены на культурах клеток HeLa и Ltk⁻ , ??а также in vivo на гепатоцитах после прямого введения белка и плазмиды pKCR2 в составе липосом в печени взрослых мышей линии BALB/c

Effect of drug utilization reviews on the quality of in-hospital prescribing: a quasi-experimental study

BACKGROUND: Drug utilization review (DUR) programs are being conducted in Canadian hospitals with the aim of improving the appropriateness of prescriptions. However, there is little evidence of their effectiveness. The objective of this study was to assess the impact of both a retrospective and a concurrent DUR programs on the quality of in-hospital prescribing. METHODS: We conducted an interrupted time series quasi-experimental study. Using explicit criteria for quality of prescribing, the natural history of cisapride prescription was established retrospectively in three university-affiliated hospitals. A retrospective DUR was implemented in one of the hospitals, a concurrent DUR in another, whereas the third hospital served as a control. An archivist abstracted records of all patients who were prescribed cisapride during the observation period. The effect of DURs relative to the control hospital was determined by comparing estimated regression coefficients from the time series models and by testing the statistical significance using a 2-tailed Student's t test. RESULTS: The concurrent DUR program significantly improved the appropriateness of prescriptions for the indication for use whereas the retrospective DUR brought about no significant effect on the quality of prescribing. CONCLUSION: Results suggest a retrospective DUR approach may not be sufficient to improve the quality of prescribing. However, a concurrent DUR strategy, with direct feedback to prescribers seems effective and should be tested in other settings with other drugs

The use of insulin declines as patients live farther from their source of care: results of a survey of adults with type 2 diabetes

BACKGROUND: Although most diabetic patients do not achieve good physiologic control, patients who live closer to their source of primary care tend to have better glycemic control than those who live farther away. We sought to assess the role of travel burden as a barrier to the use of insulin in adults with diabetes METHODS: 781 adults receiving primary care for type 2 diabetes were recruited from the Vermont Diabetes Information System. They completed postal surveys and were interviewed at home. Travel burden was estimated as the shortest possible driving distance from the patient's home to the site of primary care. Medication use, age, sex, race, marital status, education, health insurance, duration of diabetes, and frequency of care were self-reported. Body mass index was measured by a trained field interviewer. Glycemic control was measured by the glycosolated hemoglobin A1C assay. RESULTS: Driving distance was significantly associated with insulin use, controlling for the covariates and potential confounders. The odds ratio for using insulin associated with each kilometer of driving distance was 0.97 (95% confidence interval 0.95, 0.99; P = 0.01). The odds ratio for using insulin for those living within 10 km (compared to those with greater driving distances) was 2.29 (1.35, 3.88; P = 0.02). DISCUSSION: Adults with type 2 diabetes who live farther from their source of primary care are significantly less likely to use insulin. This association is not due to confounding by age, sex, race, education, income, health insurance, body mass index, duration of diabetes, use of oral agents, glycemic control, or frequency of care, and may be responsible for the poorer physiologic control noted among patients with greater travel burdens