Major histocompatibility complex-linked social signalling affects female fertility.

Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses (Equus caballus) to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males (n = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.

Sistema de grupos sanguíneos AB em felídeos neotropicais e compatibilidade com gatos domésticos / AB blood group system in neotropical felids and compatibility with domestic cats

O principal sistema de grupos sanguíneos reconhecido para gatos é o AB. Os felinos apresentam anticorpos naturais contra o antígeno do tipo sanguíneo a que não pertencem, o que torna os testes de compatibilidade e as tipagens sanguíneas importantes na prevenção de reações transfusionais. O objetivo deste estudo foi realizar a tipagem sanguínea de oito gatos-mouriscos (Puma yagouaroundi), oito jaguatiricas (Leopardus pardalis), sete gatos-palheiros (Leopardus colocolo), sete gatos domésticos (Felis catus) da raça Persa e oito gatos domésticos sem raça definida (SRD), bem como realizar testes de compatibilidade entre os tipos sanguíneos iguais das diferentes espécies, para avaliar a possibilidade de transfusões interespecíficas. A técnica empregada para a tipagem foi a hemaglutinação em tubos de ensaio. A ocorrência do tipo sanguíneo tipo A foi de 100% entre as jaguatiricas, os gatos-palheiros e os gatos Persas e de 85,72% entre os gatos SRD. A ocorrência do tipo B foi de 100% nos gatos-mouriscos e de 14,28% nos gatos SRD. Considerando os testes de compatibilidade sanguínea, 87,5% (n=4) das jaguatiricas foram incompatíveis com os gatos domésticos, 100% (n= 6) dos gatos-palheiros foram compatíveis com os gatos domésticos e 100% (n= 4) dos gatos-mouriscos foram incompatíveis com os gatos domésticos do tipo B.(AU)

The blood group system recognized for cats is AB. Antibodies against other blood types occur naturally in cats, which makes the compatibility tests and blood typing important for preventing transfusion reactions. Wild felids need blood transfusions in cases of diseases and when run over on highways. The aim of this study was to perform blood typing of eight jaguarundies (Puma yagouaroundi), eight ocelots (Leopardus pardalis), seven pampas cats (Leopardus colocolo), seven domestic cats (Felis catus) of Persian breed and eight non-pedigree domestic cats (Felis catus), and test compatibility among the different species with the same blood types, to evaluate the possibility of performing interspecific blood transfusions. We conducted the study from August to December. We used haemagglutination in test tubes for typing. The occurrence of blood type A was 100% among ocelots, pampas cats and domestic cats of Persian breed, while non-pedigree domestic cats showed 85.72%. The occurrence of type B was 100% for jaguarundis and 14.28% for non-pedigree domestic cats. Regarding blood compatibility tests, 87.5% (n= 4) of the ocelots were incompatible with domestic cats; 100% (n=6) of the pampas cats were compatible with domestic cats, while 100% (n=4) of the jaguarundis were incompatible with type B domestic cats.(AU)

A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1.

AIMS: The primary objective was to demonstrate that basal insulin peglispro (BIL) was non-inferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. MATERIALS AND METHODS: IMAGINE 1 was a Phase 3, open-label, parallel-arm study conducted in nine countries. Adults with type 1 diabetes (n = 455) were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. An electronic diary facilitated data capture and insulin dosing calculations for intensive insulin management. RESULTS: At 26 weeks, mean HbA1c was 7.06% ± 0.04% and 7.43% ± 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: -0.50 to -0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and between-day fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted.

Outbreak investigation identifies a single Listeria monocytogenes strain in sheep with different clinical manifestations, soil and water.

Listeria (L.) monocytogenes causes orally acquired infections and is of major importance in ruminants. Little is known about L. monocytogenes transmission between farm environment and ruminants. In order to determine potential sources of infection, we investigated the distribution of L. monocytogenes genetic subtypes in a sheep farm during a listeriosis outbreak by applying four subtyping methods (MALDI-TOF-MS, MLST, MLVA and PFGE). L. monocytogenes was isolated from a lamb with septicemia and from the brainstem of three sheep with encephalitis. Samples from the farm environment were screened for the presence of L. monocytogenes during the listeriosis outbreak, four weeks and eight months after. L. monocytogenes was found only in soil and water tank swabs during the outbreak. Four weeks later, following thorough cleaning of the barn, as well as eight months later, L. monocytogenes was absent in environmental samples. All environmental and clinical L. monocytogenes isolates were found to be the same strain. Our results show that the outbreak involving two different clinical syndromes was caused by a single L. monocytogenes strain and that soil and water tanks were potential infection sources during this outbreak. However, silage cannot be completely ruled out as the bales fed prior to the outbreak were not available for analysis. Faeces samples were negative, suggesting that sheep did not act as amplification hosts contributing to environmental contamination. In conclusion, farm management appears to be a crucial factor for the limitation of a listeriosis outbreak.

A 30 mK, 13.5 T scanning tunneling microscope with two independent tips.

We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of CuxBi2Se3. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 µeV.

Capillary channel flow experiments aboard the International Space Station.

In the near-weightless environment of orbiting spacecraft capillary forces dominate interfacial flow phenomena over unearthly large length scales. In current experiments aboard the International Space Station, partially open channels are being investigated to determine critical flow rate-limiting conditions above which the free surface collapses ingesting bubbles. Without the natural passive phase separating qualities of buoyancy, such ingested bubbles can in turn wreak havoc on the fluid transport systems of spacecraft. The flow channels under investigation represent geometric families of conduits with applications to liquid propellant acquisition, thermal fluids circulation, and water processing for life support. Present and near future experiments focus on transient phenomena and conduit asymmetries allowing capillary forces to replace the role of gravity to perform passive phase separations. Terrestrial applications are noted where enhanced transport via direct liquid-gas contact is desired.

[Peripheral artery disease and disorders of microcirculation in patients with diabetes mellitus]. / Periphere arterielle Verschlusskrankheit und Mikrozirkulationsstörungen bei Patienten mit Diabetes mellitus.

The increase in prevalence of diabetes mellitus and in life expectancy cause the growing number of diabetic patients with peripheral artery disease (PAD). Patients with long standing diabetes suffer frequently (about 70%) from peripheral sensory neuropathy. Therefore these patients miss the symptoms of claudication. Patients with silent ischemia will be classified to stadium I (Fontaine) instead to stadium II or III or their diagnosis will be missed at all. The clinical investigation of the food pulses should be done at least once per year in all patients with diabetes mellitus. When one or more pulses are not detectable the further diagnostic procedures should start with the measurement of the ABI (Ankle Brachial Index). In patients with mediasclerosis the measurement will give false high numbers. After early diagnosis conventional treatment may be effective. With late diagnosis in the stadium IV (Fontaine) always and especially before any amputation revascularisation should be done. Guidelines give the right choice of catheter-based or open vascular-surgical procedures.

Dimensionless scaling methods for capillary rise.

In this article the different dimensionless scaling methods for capillary rise of liquids in a tube or a porous medium are discussed. A systematic approach is taken, and the possible options are derived by means of the Buckingham pi theorem. It is found that three forces (inertial, viscous and hydrostatic forces) can be used to obtain three different scaling sets, each consisting of two dimensionless variables and one dimensionless basic parameter. From a general point of view the three scaling options are all equivalent and valid for describing the problem of capillary rise. Contrary to this we find that for certain cases (depending on the time scale and the dominant forces) one of the options can be favorable. Individually the different scalings have been discussed and used in literature previously, however, we intend to discuss the three different sets systematically in a single paper and try to evaluate when which scaling is most useful. Furthermore we investigate previous analytic solutions and determine their ranges of applicability when compared to numerical solutions of the differential equation of motion (momentum balance).

The transition from inertial to viscous flow in capillary rise.

We investigate the initial moments of capillary rise of liquids in a tube. In this period both inertia and viscous flow losses balance the pressure generated by the meniscus curvature (capillary pressure). It is known that the very first stage is purely dominated by inertial forces, where subsequently the influence of viscosity increases (visco-inertial flow). Finally the effect of inertia vanishes and the flow becomes purely viscous. In this study we derive the times and meniscus heights at which the transition between the time periods occur. This is done in an attempt to provide a method to determine a priori which terms of the momentum balance are relevant for a given problem. Analytic solutions known from previous literature are discussed and the time intervals of their validity compared. The predicted transition times and the calculated heights show good agreement with experimental results from literature. The results are also discussed in dimensionless form and the limitations of the calculations are pointed out.

The effect of evaporation on the wicking of liquids into a metallic weave.

Wicking of liquids into porous media is of great importance to many applications. One example are propellant management devices (PMD) used in spacecraft tanks. PMDs are designed to ensure gas free delivery of propellant during all acceleration conditions of the flight. This might be achieved by a metallic weave which is wetted by the propellant and thus prevents gas from entering below a critical bubble point pressure. In the case of cryogenic or volatile liquids the weave may dry out and refilling of the structure becomes an important issue. In this study we analyze the wicking of different liquids into a dry Dutch twilled weave (DTW 200 x 1400) by combining experimental and analytical approaches. Experiments were performed under isothermal and terrestrial conditions to investigate the role of evaporation for the capillary rise. The standard wicking model from Lucas and Washburn is enhanced to account for evaporation and gravity effects, too. By comparing the experimental results with the enhanced wicking model we find good qualitative agreement. It is also noted that evaporation may have a major impact on the wicking process.

An analytic solution of capillary rise restrained by gravity.

We derive an analytic solution for the capillary rise of liquids in a cylindrical tube or a porous medium in terms of height h as a function of time t. The implicit t(h) solution by Washburn is the basis for these calculations and the Lambert W function is used for its mathematical rearrangement. The original equation is derived out of the 1D momentum conservation equation and features viscous and gravity terms. Thus our h(t) solution, as it includes the gravity term (hydrostatic pressure), enables the calculation of the liquid rise behavior for longer times than the classical Lucas-Washburn equation. Based on the new equation several parameters like the steady state time and the validity of the Lucas-Washburn equation are examined. The results are also discussed in dimensionless form.

Long-term tolerability of inhaled human insulin (Exubera) in patients with poorly controlled type 2 diabetes.

OBJECTIVE: Inhaled human insulin (Exubera; EXU) has shown encouraging tolerability in short-term trials. We evaluated the safety profile of EXU after long-term exposure. DESIGN: In two, open-label, 2-year studies patients poorly controlled on a sulphonylurea were randomised to adjunctive EXU or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2). PATIENTS: The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated haemoglobin (HbA(1c)) levels of 8-12%. MEASUREMENTS: Main outcome measures were pulmonary function tests and insulin antibody assays. RESULTS: A total of 109 patients (study 1) and 195 patients (study 2) completed 104 weeks treatment. In both studies, small treatment group differences in change from baseline forced expiratory volume in 1 s were greatest at 6 months (first time-point measured) and less at later visits, and reversed on treatment discontinuation. At 2 years, differences in mean changes were -0.10 and -0.01 l in studies 1 and 2, respectively, and -0.04 l for the pooled studies. There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA(1c) or lung function changes. Glycaemic control was maintained over 2 years. CONCLUSIONS: Exubera was well tolerated during long-term use. Pulmonary function changes compared with comparator groups were small, non-progressive and reversed upon treatment discontinuation. Importantly, rates of lung function change were indistinguishable between EXU and comparator after 6 months of therapy.

Efficacy and safety of insulin glulisine in patients with type 1 diabetes.

Insulin glulisine (glulisine), a human insulin analogue with a rapid-acting time-action profile, has been developed to fulfil the mealtime (bolus) insulin requirement in patients with diabetes. The aim of this multinational, multi-centre, controlled, open-label, randomized, parallel-group study was to compare the efficacy and safety of insulin glulisine (glulisine) to that of insulin lispro (lispro) in adults diagnosed with Type 1 diabetes. Of the 683 patients randomized, 672 received treatment (339 patients received glulisine, 333 patients received lispro). Over the 26-week study, a similar reduction in mean HbA1c occurred in both groups (adjusted mean change from baseline -0.14% in both groups). The basal insulin dose was relatively unchanged from baseline in the glulisine group but increased in the lispro group (glulisine: 0.12 IU vs. lispro: 1.82 IU; p = 0.0001). As a consequence, total daily insulin dose decreased in the glulisine group but increased in the lispro group (glulisine: -0.86 IU vs. lispro: 1.01 IU; p = 0.0123). There was no relevant difference between the two groups in the reporting of symptomatic hypoglycaemia (overall, nocturnal and severe). This study demonstrates that glulisine provides equivalent glycaemic control to lispro. The clinical relevance of any difference in total daily insulin dose remains to be established.

InDuo, a novel combined insulin injection and blood glucose monitoring device - effective and save as other devices, and patient preference.

BACKGROUND AND AIM: Frequent blood glucose (BG) monitoring and insulin administration are necessary in intensive insulin regimes. A new integrated system, InDuo is a compact and portable combined insulin doser and BG monitor, designed to overcome some of the limitations of current insulin therapy. The aim of the study was to compare InDuo and a non-integrated system (HumaPen Ergo and Accu-Chek Sensor Meter) for efficacy and safety, and to evaluate patients preference. MATERIALS AND METHODS: The trial design was a multicentre, randomised, 12-week, open-label, comparative, two period crossover. One hundred and ten patients with diabetes, treated with a basal bolus regime, were included. The subjects were assigned to use either InDuo or the non-integrated system. After six weeks of treatment, the subjects were transferred to the alternative system. To assess efficacy, fasting plasma glucose (FBG), 7-point blood glucose profile, serum fructosamine and HbA1c were measured. Serum fructosamine and FBG were measured at baseline and at six and 12 weeks; HbA1c was measured at baseline and week 12. Safety endpoints were number and severity of hypoglycaemic episodes, adverse events and adverse device effects. Patient preference was assessed by a comparative device questionnaire at 12 weeks. RESULTS: Analysis with an ANOVA mixed model showed no difference after each treatment between serum fructosamine or between FBG levels. HbA1c decreased during the trial from 7.5 % +/- 1.2 to 7.1 % +/- 0.8 at 12 weeks. The safety profiles were similar for both treatments for hypoglycaemic episodes. The incidence of adverse events was also similar. There were 10 adverse device effects reported: eight for the Innovo device in the InDuo, one for the InDuo device and one for the Accu-Chek Sensor Meter. The comparative device questionnaire at 12 weeks showed patients strongly preferred InDuo to HumaPen Ergo and Accu-Chek Sensor Meter (all p < 0.0001). Of those preferring InDuo, more than 60 % classified their choice as very or extremely strong. Both memory functions in InDuo(R) (i. e., for insulin dosage and for blood glucose readings) were used by more than 70 % of the patients. CONCLUSION: Treatment with the InDuo system was as effective and safe as treatment with the non-integrated system. Almost 75 % preferred using InDuo to the non-integrated HumanPen Ergo and Accu-Chek Sensor Meter.

The effects of skin temperature and testing site on blood glucose measurements taken by a modern blood glucose monitoring device.

BACKGROUND: Modern blood glucose (BG) monitoring devices (e.g., InDuo [LifeScan, Inc., Milpitas, CA]) require very low blood volumes, allowing for testing at sites other than the traditional fingertip, but the reliability of such testing has not been fully elucidated. The aim of this randomized study was to compare the effects of cold/warm skin temperature combined with alternative site (forearm) testing versus conventional fingertip measurements on fasting and postprandial conditions. MATERIALS AND METHODS: The study population consisted of 19 patients who had previously used InDuo for 6 weeks. Four simultaneous (within 1 min) BG readings (left and right forearm and fingertips) were obtained from each patient 15, 10, and 5 min before eating. Ten minutes before eating, the patient immersed one arm in cold water (15.5 degrees C) and the other in warm water (35 degrees C). At time 0 min arms were removed from water baths, and the patient was offered a standard meal (duration 15 min). Arms were again immersed in water baths, and BG was measured from the same locations 20 min after eating and at subsequent 15-min intervals for 185 min. The effects of site testing and temperature were assessed in this period by identifying maximum BG concentrations (C (max)) and time to C (max) (T (max)). RESULTS: Significantly lower Cmax values were observed for (1) cold forearm versus cold fingertip (mean Delta 28.6 mg/dL, P < 0.001), (2) warm forearm versus warm fingertip (mean Delta 12 mg/dL, P = 0.028), (3) cold fingertip versus warm fingertip (mean Delta 17.2 mg/dL, P = 0.002), and (4) cold forearm versus warm forearm (mean Delta 33.7 mg/dL, P < 0.001). Significantly longer Tmax values were reported for cold forearm versus warm forearm (mean Delta 22.4 min, P < 0.001) and cold forearm versus cold fingertip (mean Delta 20 min, P < 0.001). CONCLUSIONS: These results demonstrate that cold skin and forearm conditions significantly underestimate BG concentrations and delay T(max) compared with warm skin and fingertip measurements.

A 75% insulin lispro/25% NPL mixture provides a longer duration of insulin activity compared with insulin lispro alone in patients with Type 1 diabetes.

AIMS: To compare a new insulin formulation, high mix (HM) [75% lispro (LP) and 25% neutral protamine lispro (NPL)], to regular human insulin (HR) and LP with respect to glucose response and pharmacokinetics following a test meal in patients with Type 1 diabetes. METHODS: After fasting overnight, patients received an intravenous insulin infusion to standardize blood glucose (BG) to 7.5 mmol/l (135 mg/dl). In a randomised, three-way crossover study, HR was injected 30 min before, and LP or HM was injected immediately before the test meal on three separate occasions. For each patient, LP and HR were administered at identical doses; the HM dose was one and one third times that of HR and LP to maintain the same dose of short or rapid-acting insulin. The insulin infusion was stopped 15 min after the insulin injection. Free insulin and BG concentrations were measured frequently for 7 h following the test meal. RESULTS: HM and LP resulted in better glycaemic control than HR during the observation period. BG concentrations during the first 4-5 h did not differ between HM and LP. However, HM exhibited prolonged insulin activity relative to LP beyond 5 h, extending the duration of action by approximately 1 h, and resulting in lower overall BG concentrations when the 0-6- and 0-7-h intervals were considered. CONCLUSIONS: Compared with LP, HM provided similar glycaemic control for up to 5 h and superior glycaemic control from 5 to 7 h following a standard test meal.