Treatment of rats with a self-selected hyperlipidic diet, increases the lipid content of the main adipose tissue sites in a proportion similar to that of the lipids in the rest of organs and tissues

Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle) 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in"other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the"rest" of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed

Exploring perceptions of Lean in the public sector

This paper explores discourses around Lean by examining the perceptions of new users of Lean in the public sector. The paper draws on actor–network theory as the basis for exploring what these new users think about Lean and uses data analysis tools to extrude concepts of significance. The data suggests that Lean continues to retain diverse, parallel and competing perspectives. The responses also signal that key concepts of Lean are missing from the discourses, and that this highlights a need to discuss Lean as a mindset—not just as a set of tools. The paper suggests future directions for research to further explore the issues emphasised by respondents

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies: A stakeholder meeting report

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs. Key discussions focused on refining trial protocols to balance statistical power with participant burden, overseen by a data safety monitoring board. The meeting emphasised the importance of harmonizing CHIM protocols to ensure robust, reproducible, and transparent research. Mandatory trial registration and adherence to the Findable, Accessible, Interoperable, and Reusable (FAIR) data principles were recommended to enhance data reuse and scientific value. This report consolidates efforts to standardise CHIM protocols, essential for accelerating therapeutic innovations and advancing global health research

Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d’Ivoire

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d’Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose–response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22–43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r2 = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures

Influence of Finite Hydraulic-Fracture Conductivity on Unconventional Hydrocarbon Recovery With Horizontal Wells

Summary The classic plots of dimensionless fracture conductivity (CfD) vs. equivalent wellbore radius or equivalent negative skin are useful for evaluating the performance of hydraulic fractures (HFs) in vertical wells targeting conventional reservoirs (Prats 1961; Cinco-Ley and Samaniego-V. 1981). The increase in well productivity after hydraulic stimulation can be estimated from the “after fracturing” effective wellbore radius or from the “after fracturing” equivalent negative skin. However, this earlier work does not apply to the case of horizontal wells with multiple fractures. A revision of the diagnostic plots is needed to account for the combination of the resulting radial-flow regime and the transient effect in unconventional reservoirs with ultralow permeability. This paper reviews and extends this earlier work with the objective of making it applicable in the case of horizontal wells with multiple fractures. It also demonstrates practical application of this new technique for fracture-design optimization for horizontal wells. The influence of finite fracture conductivity (FC) on the HF flow efficiency is evaluated through analytical models, and it is confirmed by a 3D transient numerical-reservoir simulation. This work demonstrates that a redefined dimensionless fracture conductivity for horizontal wells CfD,h = 4 is found to be optimal by use of the maximum of log-normal derivative (subject to economics) for HFs in horizontal wells, and this value of CfD,h can provide 50% of the fracture-flow efficiency and 90% of the estimated ultimate recovery (EUR) that would have been obtained from an infinitely conductive fracture for the same production period. This new master plot can provide guidance for hydraulic-fracturing design and its optimization for hydrocarbon recovery in unconventional reservoirs through hydraulic fracturing in horizontal wells.</jats:p