Mcintyrealbrektsen5347

Understanding how breaks form and are repaired in the genome depends on the accurate measurement of the frequency and position of DNA double strand breaks (DSBs). This is crucial for identification of a chemical's DNA damage potential and for safe development of therapies, including genome editing technologies. Current DSB sequencing methods suffer from high background levels, the inability to accurately measure low frequency endogenous breaks and high sequencing costs. Here we describe INDUCE-seq, which overcomes these problems, detecting simultaneously the presence of low-level endogenous DSBs caused by physiological processes, and higher-level recurrent breaks induced by restriction enzymes or CRISPR-Cas nucleases. INDUCE-seq exploits an innovative NGS flow cell enrichment method, permitting the digital detection of breaks. It can therefore be used to determine the mechanism of DSB repair and to facilitate safe development of therapeutic genome editing. We further discuss how the method can be adapted to detect other genomic features.We used a compiled data set from a monitoring network of oyster production coordinated by IFREMER (the French Research Institute for the Exploitation of the Sea). This network monitors the growth and mortality of the Pacific oyster Crassostrea gigas along French coasts since 1993. The archive, although publicly available, has been challenging to use due to changes in protocols and little information on metadata. Here, we describe data collection for almost 30 years, cleaning and processing. For 13 locations, we modeled growth and mortality of spat (less than one-year-old individuals) and half-grown oysters (between one and two-year-old individuals) as a function of time to cope with changes in data acquisition frequency, and produced standardized annual growth and cumulative mortality indicators to improve data usability. This improved database is expected to be used by ecologists interested in the evolution of life-cycle indicators of a marine species under the influence of climate change. It can also be valuable for epidemiologists because mortality data traces the emergence and spread of a massive epizootic.Atomically-thin van der Waals layered materials, with both high in-plane stiffness and bending flexibility, offer a unique platform for thermomechanical engineering. find more However, the lack of effective characterization techniques hinders the development of this research topic. Here, we develop a direct experimental method and effective theoretical model to study the mechanical, thermal, and interlayer properties of van der Waals materials. This is accomplished by using a carefully designed WSe2-based heterostructure, where monolayer WSe2 serves as an in-situ strain meter. Combining experimental results and theoretical modelling, we are able to resolve the shear deformation and interlayer shear thermal deformation of each individual layer quantitatively in van der Waals materials. Our approach also provides important interlayer coupling information as well as key thermal parameters. The model can be applied to van der Waals materials with different layer numbers and various boundary conditions for both thermally-induced and mechanically-induced deformations.The development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10-8 to 10-17 M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2'C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds.Rehabilitation of the neurologic horse represents a unique challenge for the equine practitioner. Improving postural stability and balance control through improving the strength of the spinal stabilizer muscle multifidus remains one of the most promising rehabilitative targets. This muscle can be targeted through the use of physiotherapeutic exercises, various forms of perturbation, and even whole-body vibration. Neuroanatomic localization and diagnosis specificity enable the practitioner to determine suitability for such rehabilitative tasks, and with the advent of evolving strategies and commercially available equipment, the bandwidth for professionally guided programs is continuously being developed and is expected to improve traditional outcomes.Advances in the understanding of equine protozoal myeloencephalitis (EPM) are reviewed. It is now apparent that EPM can be caused by either of 2 related protozoan parasites, Sarcocystis neurona and Neospora hughesi, although S neurona is the most common etiologic pathogen. Horses are commonly infected, but clinical disease occurs only infrequently; the factors influencing disease occurrence are not well understood. Epidemiologic studies have identified risk factors for the development of EPM, including the presence of opossums and prior stressful health-related events. Attempts to reproduce EPM experimentally have reliably induced antibody responses in challenged horses, but have not consistently produced neurologic disease. Diagnosis of EPM has improved by detecting intrathecal antibody production against the parasite. Sulfadiazine/pyrimethamine (ReBalance) and the triazine compounds diclazuril (Protazil) and ponazuril (Marquis) are effective anticoccidial drugs that are now available as FDA-approved treatments for EPM.Mechanisms of traumatic nervous system injury to a degree are similar, but differences exist in etiology, pathophysiology, and treatment of brain, spinal cord, and peripheral nerve injury. The most common clinical abnormalities seen in the horse are abnormal level of consciousness, abnormal behavior, seizures, cranial nerve deficits, vestibular disease, tetra- and paraparesis or paraplegia, cauda equina syndrome, specific gait deficits, and muscle atrophy. Treatments are directed toward reducing inflammation and swelling, halting secondary injury, and promoting mechanisms of neuroregeneration and plasticity. Prognosis depends on the severity of primary injury and the neuroanatomic location and extent of nervous tissue damage.The variety of neurologic diseases which affect horses makes pathologic examination of the nervous system a complex and lengthy process. An understanding of the common causes of neurologic disease, antemortem neurolocalization, and supplementation of the necropsy examination with ancillary testing will help to diagnose a large number of causes of neurologic disease. A general understanding of neuropathology and collaborative relationship with your local pathologists will aid in the definitive diagnosis of neurologic diseases.Diagnostic imaging is often an important part of the diagnostic approach to neurologic disease. Advanced imaging techniques such as myelography, computed tomography (CT), and magnetic resonance imaging (MRI) provide more information than radiography and ultrasonography but are more limited in their availability. The clinician should be cognizant of the findings of the clinical examination when interpreting diagnostic imaging findings.

To establish cut-points and thresholds for elevated diabetes distress; document change over time; and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS).

A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational "threshold" approach defined elevated SOURCE scores.

471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8% (69.9% over 6months). Elevated SOURCE scores varied from 30.6% (Stigma/Shame) to 76.4% (Management); 87.5% indicated at least 1 elevated SOURCE score. Most (77.1%) reported multiple elevated SOURCES. 81.8% with elevated CORE distress at baseline remained elevated at 6months. MCID analyses yielded +/- 0.25 as significant change. Few differences between insulin- and non-insulin users occurred.

Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

To evaluate the overall association between clinically significant nocturnal hypoglycemia (CsNH) and risk factors in geriatric patients with type 2 diabetes.

Overall, 606 geriatric with type 2 diabetes were evaluated for CsNH using Freestyle Libre Pro® (Abbott Diabetes Care, Tokyo, Japan) during October 2018-February 2020. We defined CsNH as blood glucose level <54mg/dL (3.0mmol/L). We investigated clinical characteristics and efficacies of hypoglycemic agents and insulin and analyzed CsNH risk factors using univariate and multivariate logistic regression analyses.

We enrolled 152 patients each for the CsNH and non-nocturnal hypoglycemia groups. Insulin use (OR=3.77 [95% CI 1.92-7.67]; P=0.0002), age (OR=1.06 [95% CI 1.01-1.12]; P=0.0492), estimated glomerular filtration rate (OR=0.97 [95% CI 0.95-0.98]; P=0.0492), and fasting blood glucose level (OR=0.94 [95% CI 0.91-0.94]; P<0.0001) were independent CsNH risk factors. The combined results demonstrated a higher predictability of CsNH than each of the individual risk factors.

We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines.

We retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care.

The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.