Gene Correction Reduces Cutaneous Inflammation and Granuloma Formation in Murine X-Linked Chronic Granulomatous Disease

Our laboratory previously demonstrated that X-linked chronic granulomatous disease (X-CGD) mice develop exaggerated inflammatory responses and form granulomas following intradermal challenge with sterile Aspergillus fumigatus (AF) hyphae. In this study, we examined the efficacy of retroviral-mediated gene transfer (RMGT) into X-CGD bone marrow stem cells in preventing this abnormal inflammatory response. Sterile AF or saline was injected subcutaneously into the ears of wild-type, female X-CGD carrier, X-CGD, or X-CGD mice chimeric for varying numbers of either wild-type or RMGT-corrected neutrophils. Intradermal AF induced marked inflammation at both 3 and 30 d in the X-CGD mice, but not in the carriers or the wild-type mice. Similar to wild-type mice, chimeric X-CGD mice with >20% oxidase-positive neutrophils displayed a minimal and self-limited inflammatory response. Inflammation in chimeric (both wild-type and RMGT-corrected) mice with <15% oxidase-positive neutrophils was also improved compared to X-CGD mice, although still abnormal. This is the first evidence that partial correction of NADPH oxidase activity by gene therapy is likely to be beneficial in reducing or preventing the chronic inflammatory complications of CGD patients if sufficient numbers of RMGT-corrected neutrophils are obtained

A Model for Force Fluctuations in Bead Packs

We study theoretically the complex network of forces that is responsible for the static structure and properties of granular materials. We present detailed calculations for a model in which the fluctuations in the force distribution arise because of variations in the contact angles and the constraints imposed by the force balance on each bead of the pile. We compare our results for force distribution function for this model, including exact results for certain contact angle probability distributions, with numerical simulations of force distributions in random sphere packings. This model reproduces many aspects of the force distribution observed both in experiment and in numerical simulations of sphere packings

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Bullet Hole

Photograph used for a story in the Oklahoma Times newspaper. Caption: "Bullet hole in the front plate glass window of the Twenty-Third and Walker liquor store was discovered Monday by Joe Ross.

Thermal energy storage for gas turbine power augmentation

This work is concerned with the investigation of thermal energy storage (TES) in relation to gas turbine inlet air cooling. The utilization of such techniques in simple gas turbine or combined cycle plants leads to improvement of flexibility and overall performance. Its scope is to review the various methods used to provide gas turbine power augmentation through inlet cooling and focus on the rising opportunities when these are combined with thermal energy storage. The results show that there is great potential in such systems due to their capability to provide intake conditioning of the gas turbine, decoupled from the ambient conditions. Moreover, latent heat TES have the strongest potential (compared to sensible heat TES) towards integrated inlet conditioning systems, making them a comparable solution to the more conventional cooling methods and uniquely suitable for energy production applications where stabilization of GT air inlet temperature is a requisite. Considering the system’s thermos-physical, environmental and economic characteristics, employing TES leads to more than 10% power augmentation.QC 20201021H2020 Pump Hea

Expiratory reactance abnormalities in patients with expiratory dynamic airway collapse: a new application of impulse oscillometry

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC. EDAC was identified at bronchoscopy as 75–100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC. 38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls). These data show a new utility of IOS: detecting EDAC in patients with normal lung function