The corona contracts in a black-hole transient.

The geometry of the accretion flow around stellar-mass black holes can change on timescales of days to months1-3. When a black hole emerges from quiescence (that is, it 'turns on' after accreting material from its companion) it has a very hard (high-energy) X-ray spectrum produced by a hot corona4,5 positioned above its accretion disk, and then transitions to a soft (lower-energy) spectrum dominated by emission from the geometrically thin accretion disk, which extends to the innermost stable circular orbit6,7. Much debate persists over how this transition occurs and whether it is driven largely by a reduction in the truncation radius of the disk8,9 or by a reduction in the spatial extent of the corona10,11. Observations of X-ray reverberation lags in supermassive black-hole systems12,13 suggest that the corona is compact and that the disk extends nearly to the central black hole14,15. Observations of stellar-mass black holes, however, reveal equivalent (mass-scaled) reverberation lags that are much larger16, leading to the suggestion that the accretion disk in the hard-X-ray state of stellar-mass black holes is truncated at a few hundreds of gravitational radii from the black hole17,18. Here we report X-ray observations of the black-hole transient MAXI J1820+07019,20. We find that the reverberation time lags between the continuum-emitting corona and the irradiated accretion disk are 6 to 20 times shorter than previously seen. The timescale of the reverberation lags shortens by an order of magnitude over a period of weeks, whereas the shape of the broadened iron K emission line remains remarkably constant. This suggests a reduction in the spatial extent of the corona, rather than a change in the inner edge of the accretion disk.

Lightwave valleytronics in a monolayer of tungsten diselenide.

As conventional electronics approaches its limits 1 , nanoscience has urgently sought methods of fast control of electrons at the fundamental quantum level 2 . Lightwave electronics 3 -the foundation of attosecond science 4 -uses the oscillating carrier wave of intense light pulses to control the translational motion of the electron's charge faster than a single cycle of light5-15. Despite being particularly promising information carriers, the internal quantum attributes of spin 16 and valley pseudospin17-21 have not been switchable on the subcycle scale. Here we demonstrate lightwave-driven changes of the valley pseudospin and introduce distinct signatures in the optical readout. Photogenerated electron-hole pairs in a monolayer of tungsten diselenide are accelerated and collided by a strong lightwave. The emergence of high-odd-order sidebands and anomalous changes in their polarization direction directly attest to the ultrafast pseudospin dynamics. Quantitative computations combining density functional theory with a non-perturbative quantum many-body approach assign the polarization of the sidebands to a lightwave-induced change of the valley pseudospin and confirm that the process is coherent and adiabatic. Our work opens the door to systematic valleytronic logic at optical clock rates.

Lightwave-driven quasiparticle collisions on a subcycle timescale.

Ever since Ernest Rutherford scattered α-particles from gold foils, collision experiments have revealed insights into atoms, nuclei and elementary particles. In solids, many-body correlations lead to characteristic resonances--called quasiparticles--such as excitons, dropletons, polarons and Cooper pairs. The structure and dynamics of quasiparticles are important because they define macroscopic phenomena such as Mott insulating states, spontaneous spin- and charge-order, and high-temperature superconductivity. However, the extremely short lifetimes of these entities make practical implementations of a suitable collider challenging. Here we exploit lightwave-driven charge transport, the foundation of attosecond science, to explore ultrafast quasiparticle collisions directly in the time domain: a femtosecond optical pulse creates excitonic electron-hole pairs in the layered dichalcogenide tungsten diselenide while a strong terahertz field accelerates and collides the electrons with the holes. The underlying dynamics of the wave packets, including collision, pair annihilation, quantum interference and dephasing, are detected as light emission in high-order spectral sidebands of the optical excitation. A full quantum theory explains our observations microscopically. This approach enables collision experiments with various complex quasiparticles and suggests a promising new way of generating sub-femtosecond pulses.

Relationship of arsenic and chromium availability with carbon functional groups, aluminum and iron in Little Washita River Experimental Watershed Reservoirs, Oklahoma, USA.

Sediment from three reservoirs located in the Little Washita River Experimental Watershed (LWREW) in Oklahoma, USA with contrasting dominant land uses were analyzed for total and extractable concentrations of arsenic (As) and chromium (Cr), and the potential ecologic risk to benthic organisms. Extractable As ranged from 0.24 to 1.21 mg kg-1, in the order grazing>cropland>forest and 0.13-0.58 mg kg-1 for extractable Cr, in the order of forest>grazing>cropland. However, only approximately < 1.5% of total As and < 4% of total Cr were extractable. Total As ranged from 16.2 to 141 mg kg-1 and total Cr ranged from 5.06 to 40.1 mg kg-1 both in the order of cropland>grazing>forest. The sediment exhibited an alkaline pH (8.0-8.7). As sorption exhibited a positive relationship with Al (r = 0.9995; P = 0.0001), Fe (r = 0.9829; P = 0.0001), and C (r = 0.4090; P = 0.0017) and Cr correlated positively with Al (r = 0.9676 P = 0.0001), Fe (r = 0.9818; P = 0.0001), and C (r = 0.3368; P = 0.0111). In addition, both As and Cr exhibited positive relationships with carbon (C) functional groups in the order of O-alkyl C> methoxyl C> alkyl C> aromatic C> carboxyl C> phenolic C. The sediment concentration analysis results illustrated that As in all reservoirs exceeded their respective Threshold Effect Level (TEL) and/or Probable Effect Level (PEL) indicating that existing concentrations of metals in these sediments were sufficiently high to cause adverse effects. However, Cr concentrations in all reservoirs evaluated was lower compared to the TEL and PEL.

The validity of an experiment testing the influence of acceleration on time dilation using a rotating Mössbauer absorber and a Synchrotron Mössbauer Source.

Three experiments are reviewed, performed (in 2014-2016) at ID18 of ESRF to measure the influence of acceleration on time dilation by measuring the relative shift between the absorption lines of two states of the same rotating absorber with accelerations anti-parallel and parallel to the incident beam. Statistically significant data for rotation frequencies up to 510 Hz in both directions of rotation were collected. For each run with high rotation, a stable statistically significant `vibration-free' relative shift between the absorption lines of the two states was measured. This may indicate the influence of acceleration on time dilation. However, the measured relative shift was also affected by the use of a slit necessary to focus the beam to the axis of rotation to a focal spot of sub-micrometre size. The introduction of the slit broke the symmetry in the absorption lines due to the nuclear lighthouse effect and affected the measured relative shift, preventing to claim conclusively the influence of acceleration on time dilation. Assuming that this loss of symmetry is of first order, the zero value of the relative shift, corrected for this loss, falls always within the experimental error limits, as predicted by Einstein's clock hypothesis. The requirements and an indispensable plan for a conclusive experiment, once the improved technology becomes available, is presented. This will be useful to future experimentalists wishing to pursue this experiment or a related rotor experiment involving a Mössbauer absorber and a synchrotron Mössbauer source.

Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

All naturally occurring autoantibodies against the NMDA receptor subunit NR1 have pathogenic potential irrespective of epitope and immunoglobulin class.

Autoantibodies of the IgG class against N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) were first described in anti-NMDAR encephalitis and seen as disease indicators. Recent work on together over 5000 individuals challenged this exclusive view by showing age-dependently up to >20% NMDAR1-autoantibody seroprevalence with comparable immunoglobulin class and titer distribution across health and disease. The key question therefore is to understand the properties of these autoantibodies, also in healthy carriers, in order to assess secondary complications and possible contributions to neuropsychiatric disease. Here, we believe we provide for human NMDAR1-autoantibodies the first comprehensive analysis of their target epitopes and functionality. We selected sera of representative carriers, healthy or diagnosed with very diverse conditions, that is, schizophrenia, age-related disorders like hypertension and diabetes, or anti-NMDAR encephalitis. We show that all positive sera investigated, regardless of source (ill or healthy donor) and immunoglobulin class, provoked NMDAR1 internalization in human-induced pluripotent stem cell-derived neurons and reduction of glutamate-evoked currents in NR1-1b/NR2A-expressing Xenopus oocytes. They displayed frequently polyclonal/polyspecific epitope recognition in the extracellular or intracellular NMDAR1 domains and some additionally in NR2A. We conclude that all circulating NMDAR1-autoantibodies have pathogenic potential regarding the whole spectrum of neuronal NMDAR-mediated effects upon access to the brain in situations of increased blood-brain-barrier permeability.

Advancing the Sustainability of US Agriculture through Long-Term Research.

Agriculture in the United States must respond to escalating demands for productivity and efficiency, as well as pressures to improve its stewardship of natural resources. Growing global population and changing diets, combined with a greater societal awareness of agriculture's role in delivering ecosystem services beyond food, feed, fiber, and energy production, require a comprehensive perspective on where and how US agriculture can be sustainably intensified, that is, made more productive without exacerbating local and off-site environmental concerns. The USDA's Long-Term Agroecosystem Research (LTAR) network is composed of 18 locations distributed across the contiguous United States working together to integrate national and local agricultural priorities and advance the sustainable intensification of US agriculture. We explore here the concept of sustainable intensification as a framework for defining strategies to enhance production, environmental, and rural prosperity outcomes from agricultural systems. We also elucidate the diversity of factors that have shaped the past and present conditions of cropland, rangeland, and pastureland agroecosystems represented by the LTAR network and identify priorities for research in the areas of production, resource conservation and environmental quality, and rural prosperity. Ultimately, integrated long-term research on sustainable intensification at the national scale is critical to developing practices and programs that can anticipate and address challenges before they become crises.

[Autoimmune encephalitis with psychotic symptoms : Diagnostics, warning signs and practical approach]. / Autoimmunenzephalitis mit psychotischer Symptomatik : Diagnostik, Warnhinweise und praktisches Vorgehen.

Despite intensive research, a precise cause of schizophrenic and schizoaffective disorders has not yet been identified. Therefore, psychiatric diagnoses are still made based on clinical ICD-10/DSM­5 criteria and not on any objective markers; however, various causes or pathophysiological processes may ultimately lead to similar symptoms. An important task for the future of psychiatry is to identify disease subtypes with a distinct pathophysiology to develop more specific and causally acting therapies. A new diagnostic entity has become established in clinical neurology and psychiatry in recent years: autoimmune encephalitis with psychotic symptoms caused by specific antineuronal antibodies has been identified as a rare but potentially treatable cause of psychotic disorders; however, these inflammatory brain diseases are not reliably detected by routine psychiatric diagnostics. Therefore, this qualitative review is intended to provide structured support for clinical practice, which, guided by clinical warning signals, enables a rapid and reliable diagnosis as well as the initiation of immunotherapy. In the case of psychiatric symptoms, the additional onset of focal neurological signs, disturbances of consciousness and orientation, autonomic instability or epileptic seizures and electroencephalograph (EEG) abnormalities should always be followed by a more specific cerebrospinal fluid analysis with determination of antineuronal autoantibodies. Although the scientific evidence indicates that only a small subgroup of patients is affected, the swift and correct diagnosis is of high therapeutic and prognostic relevance for the affected individuals.

Advances in testing the effect of acceleration on time dilation using a synchrotron Mössbauer source.

New results, additional techniques and know-how acquired, developed and employed in a recent HC-1898 experiment at the Nuclear Resonance Beamline ID18 of ESRF are presented, in the quest to explore the acceleration effect on time dilation. Using the specially modified Synchrotron Mössbauer Source and KB-optics together with a rotating single-line semicircular Mössbauer absorber on the rim of a specially designed rotating disk, the aim was to measure the relative spectral shift between the spectra of two states when the acceleration of the absorber is anti-parallel and parallel to the source. A control system was used for the first time and a method to quantify the effects of non-random vibrations on the spectral shift was developed. For several runs where the effect of these vibrations was negligible, a stable statistically significant non-zero relative shift was observed. This suggests the influence of acceleration on time.

Anomalous Hall Effect in Type-I Weyl Metals.

We study the ac anomalous Hall conductivity σ_{xy}(ω) of a Weyl semimetal with broken time-reversal symmetry. Even in the absence of free carriers these materials exhibit a "universal" anomalous Hall response determined solely by the locations of the Weyl nodes. We show that the free carriers, which are generically present in an undoped Weyl semimetal, give an additional contribution to the ac Hall conductivity. We elucidate the phy146sical mechanism of the effect and develop a microscopic theory of the free carrier contribution to σ_{xy}(ω). The latter can be expressed in terms of a small number of parameters (the electron velocity matrix, the Fermi energy µ, and the "tilt" of the Weyl cone). The resulting σ_{xy}(ω) has resonant features at ω∼2µ which may be used to separate the free carrier response from the filled-band response using, for example, Kerr effect measurements. This may serve as a diagnostic tool to characterize the doping of individual valleys.

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.

The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.

Natural and artificial hyperimmune solutions: Impact on health in puppies.

Colostrum and milk are complex mammary secretions providing the puppy with many nutritional and immunological factors, which play a crucial role for its correct development and survival. In the case of colostrum and/or milk intake deficiency, puppies are at increased risk of infectious diseases. This work reviews the various nutritional hyperimmune supplementations proposed to provide a passive immune protection and to positively impact puppies' health. Some strategies rely on canine immunoglobulins: canine colostrum banking and canine serum/plasma supplementation. Others involve heterologous sources of antibodies and other immune factors: bovine colostrum or hyperimmune egg powder. Among the different solutions evaluated from birth to weaning, canine plasma and hyperimmune egg powder showed promising beneficial effect on puppies' health. Canine plasma seems to positively impact not only growth (increased growth during the neonatal period), but also digestive health (higher species richness of intestinal microbiota) and the general health (tendency of lower morbidity). Puppies supplemented with hyperimmune egg powder presented increased neonatal growth and decreased risk of canine parvovirus infection. Nevertheless, natural canine maternal colostrum and milk ingestion remains the optimal guarantee for puppies' health and survival, as a source of immunity, energy and growth factors.

Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications.

It has been postulated that schizophrenia (SZ) is related to a lower expression of brain-derived neurotrophic factor (BDNF). In the past few years, an increasing number of divergent clinical studies assessing BDNF in serum and plasma have been published. It is now possible to verify the relationship between BDNF levels and severity of symptoms in SZ as well as the effects of antipsychotic drugs on BDNF using meta-analysis. The aims of this study were to verify if peripheral BDNF is decreased in SZ, whether its levels are correlated with positive and negative symptomatology and if BDNF levels change after antipsychotic treatment. This report consists of two distinct meta-analyses of peripheral BDNF in SZ including a total of 41 studies and more than 7000 participants: (1) peripheral BDNF levels in serum and plasma were moderately reduced in SZ compared with controls. Notably, this decrease was accentuated with the disease duration. However, the extent of peripheral BDNF level decrease did not correlate with the severity of positive and negative symptoms. (2) In plasma, but not serum, peripheral BDNF levels are consistently increased after antipsychotic treatment irrespective of the patient's response to medication. In conclusion, there is compelling evidence that there are decreased levels of peripheral BDNF in SZ, in parallel to previously described reduced cerebral BDNF expression. It remains unclear whether these systemic changes are causally related to the development of SZ or if they are merely a pathologic epiphenomenon.

Use of deep laryngeal oxygen insufflation during laryngoscopy in children: a randomized clinical trial.

BACKGROUND: Brief periods of haemoglobin oxygen desaturation are common in children during induction of general anaesthesia. We tested the hypothesis that oxygen insufflation during intubation slows desaturation. METHODS: Patients 1-17 yr old undergoing nasotracheal intubation were enrolled and randomly assigned to one of three groups: standard direct laryngoscopy (DL); laryngoscopy with Truview PCD videolaryngoscope (VLO2); or laryngoscopy with an oxygen cannula attached to the side of a standard laryngoscope (DLO2). The co-primary outcomes were time to 1% reduction in [Formula: see text] from baseline, and the slope of overall desaturation vs time. All three groups were compared against each other. RESULTS: Data from 457 patients were available for the final analysis: 159 (35%) DL; 145 (32%) DLO2; and 153 (33%) VLO2. Both VLO2 and DLO2 were superior to DL in both time to a 1% reduction in [Formula: see text] from baseline and the overall rate of desaturation (all P<0.001). The 25th percentile (95% confidence interval) of time to a 1% saturation decrease was 30 (24, 39) s for DL, 67 (35, 149) s for DLO2 and 75 (37, 122) s for VLO2. Mean desaturation slope was 0.13 (0.11, 0.15)% s(-1) for DL, 0.04 (0.02, 0.06)% s(-1) for DLO2 and 0.03 (0.004, 0.05)% s(-1) for VLO2. We did not find a correlation between decrease in [Formula: see text] percentage and BMI or age. CONCLUSIONS: Laryngeal oxygen insufflation increases the time to 1% desaturation and reduces the overall rate of desaturation during laryngoscopy in children. CLINICAL TRIAL REGISTRATION: NCT01886807.

Assessment of Pharmacological Treatment Quality: Comparison of Symptom-triggered vs. Fixed-schedule Alcohol Withdrawal in Clinical Practice.

Introduction: Despite the fact, that symptom-triggered alcohol withdrawal treatment is recommended by German guidelines on alcoholism, many hospitals continue to use fixed-schedule protocols, as they have been successfully applied for many years. Methods: This retrospective study compared all patients' records of alcohol withdrawal treatment from October 2010 to November 2011 at Magdeburg's University Department of Psychiatry (n=120). A symptom-triggered protocol with clomethiazole (AESB, n=46) was used in parallel with the existing fixed-schedule protocol with diazepam (n=74). Results: The symptom-triggered group showed less need of pharmacological treatment duration (p<0.001) and cumulative dosage of medication compared to the fixed-schedule protocol (p<0.006). No difference was observed regarding the need of clonidine or haloperidol (to treat blood pressure derailment or delirium) and the incidence of epileptic seizures. Discussion: Based on the shorter treatment duration and a similar rate of complications our department has switched to the symptom-triggered protocol to improve the quality of patient care.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

New Short-Lived Isotope

Two short-lived isotopes ^{221}U and ^{222}U were produced as evaporation residues in the fusion reaction ^{50}Ti+^{176}Yb at the gas-filled recoil separator TASCA. An α decay with an energy of E_{α}=9.31(5) MeV and half-life T_{1/2}=4.7(7) µs was attributed to ^{222}U. The new isotope ^{221}U was identified in α-decay chains starting with E_{α}=9.71(5) MeV and T_{1/2}=0.66(14) µs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.

Impact on glycated haemoglobin of a biological response-based measure of medication adherence.

AIMS: The aim of this study was to examine the relationship between a specific glycated haemoglobin (HbA1c) measurement and a pharmaceutical dispensings-based measure of adherence calculated over the 90 days before each HbA1c measure among patients who have newly initiated metformin therapy. METHODS: We identified 3109 people with type 2 diabetes who initiated metformin as their first-ever antihyperglycaemic drug, analysing all 9918 HbA1c measurements that were taken over the next 2 years. We used an adaptation of the 'proportion of days covered' method for assessing medication adherence that corresponded to an ∼90-day interval preceding an HbA1c measurement, terming the adaptation the 'biological response-based proportion of days covered' (BRB-PDC). To account for multiple observations per patient, we analysed the association between HbA1c and BRB-PDC within the generalized estimating equation framework. Analyses were stratified by HbA1c level before metformin initiation using a threshold of 8% (64 mmol/mol). RESULTS: After multivariable adjustment using 0% adherence as the reference category, BRB-PDC in the range 50-79% was associated with HbA1c values lower by -0.113 [95% confidence interval (CI) -0.202, -0.025] among patients with pre-metformin HbA1c <8%, and by -0.247 (95% CI -0.390, -0.104) among those with HbA1c ≥8% at metformin initiation. Full adherence (≥80%) was associated with HbA1c values lower by -0.175% (95% CI -0.257, -0.093) and by -0.453% (95% CI -0.586, -0.320). CONCLUSIONS: Using this novel short-interval approach that more closely associates adherence with the expected biological response, the association between better adherence and HbA1c levels was considerably stronger than has been previously reported; however, the strength of the impact was dependent upon the HbA1c level before initiating metformin.

Association of DLA-DQB1 alleles with exocrine pancreatic insufficiency in Pembroke Welsh Corgis.

Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse breeds, to date, molecular studies have been limited to the German Shepherd dog. A recent study of major histocompatibility genes in diseased and healthy German Shepherd dogs identified both risk and protective haplotypes. Herein, we genotyped DLA-DQB1 in Pembroke Welsh Corgis to determine whether dog leukocyte antigen alleles contribute to the pathogenesis of EPI across dog breeds. We evaluated 14 affected and 43 control Pembroke Welsh Corgis, which were selected based on an age of onset similar to German Shepherd dogs. We identified one protective allele (odds ratio = 0.13, P-value = 0.044) and one risk allele (odds ratio = 3.8, P-value = 0.047). As in German Shepherd dogs, the risk allele is a duplication of DLA-DQB1 (alleles DQB1*013:03 and 017:01); however, Pembroke Welsh Corgis have acquired a single polymorphism on DQB1*017:01. Thus, the DLA-DQB1 duplication is a risk allele for EPI in at least two breeds.