Search

To synthesize existing literature regarding the indications and outcomes of femoral rotational osteotomies (FDO) for femoroacetabular impingement (FAI) due to.

Following Sylvia Wynter’s call to historicize the human, we bring the posthumanist deconstruction of humanism in conversation with the Black feminist praxis of sociogeny. By situating modern categories of race, gender, sexuality, and the human itself within their colonial legacies of knowledge production, we trace the colonial archetype of the human as Man, and how we might disrupt this ever-present monolithic paradigm. To that end, we turn to Hippolyta Freeman, a character in the afrofuturist science-fiction horror television show Lovecraft Country, to explore genres of being human beyond the prevailing order of Man.

BackgroundConsistent patterns of reduced cortical thickness have been identified in early Alzheimer’s disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear.MethodsParticipants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral β-amyloid (Aβ) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years).ResultsIn a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aβ status did not. Among Aβ positive participants (n=56), there was some evidence that greater global Aβ standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08).ConclusionsCortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aβ-positivity, robust Aβ-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset.

Background: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. Method: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. Results: 1874 patients from 159 centres across 52 countries were included. 78.3% (n= 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n= 910) and 9.3% (n= 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n= 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4–2), (OR = 4.7, 95% CI 3.1–7.6)], female gender [(OR = 1.8, 95% CI 1.4–2.3), (OR = 1.9, 95% CI 1.3–2.9)], shock on admission [(OR = 2.1, 95% CI 1.7–2.7), (OR = 4.8, 95% CI 3.2–7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9–3.2), (OR = 3.9), 95% CI 2.7–5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1–1.6], but not mortality. Conclusions: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality. Graphical abstract:

High impact recent articles have reported on the existence of a liquid–liquid (L–L) phase transition as a function of both pressure and temperature in ionic liquids (ILs) containing the popular trihexyltetradecylphosphonium cation (P666,14+), sometimes referred to as the “universal liquifier”. The work presented here reports on the structural-dynamic pathway from liquid to glass of the most well-studied IL comprising the P666,14+cation. We present experimental and computational evidence that, on cooling, the path from the room-temperature liquid to the glass state is one of separate structural-dynamic changes. The first stage involves the slowdown of the charge network, while the apolar subcomponent is fully mobile. A second, separate stage entails the slowdown of the apolar domain. Whereas it is possible that these processes may be related to the liquid–liquid and glass transitions, more research is needed to establish this conclusively.

Pediatric interfacility transport teams facilitate access to subspecialty care, and physicians often guide management remotely as transport medical control (TMC). Pediatric subspecialty fellows frequently perform TMC duties, but tools assessing competency are lacking. Our objective was to develop content validity for the items required to assess pediatric subspecialty fellows’ TMC skills.We conducted a modified Delphi process among transport and fellow education experts in pediatric critical care medicine, pediatric emergency medicine, neonatal-perinatal medicine, and pediatric hospital medicine. The study team generated an initial list of items on the basis of a literature review and personal experience. A modified Delphi panel of transport experts was recruited to participate in 3 rounds of anonymous, online voting on the importance of the items using a 3-point Likert scale (marginal, important, essential). We defined consensus for inclusion as ≥80% agreement that an item was important/essential and consensus for exclusion as ≥80% agreement that an item was marginal.The study team of 20 faculty drafted an initial list of items. Ten additional experts in each subspecialty served on the modified Delphi panel. Thirty-six items met the criteria for inclusion, with widespread agreement across subspecialties. Only 1 item, “discussed bed availability,” met the criteria for inclusion among some subspecialties but not others. The study team consolidated the final list into 26 items for ease of use.Through a consensus-based process among transport experts, we generated content validity for the items required to assess pediatric subspecialty fellows’ TMC skills.

Background: The health burden caused by seasonal influenza is substantial. We sought to examine the effectiveness of influenza vaccination against admission to hospital for acute cardiovascular and respiratory conditions and all-cause death in people with type 2 diabetes. Methods: We conducted a retrospective cohort study using primary and secondary care data from the Clinical Practice Research Datalink in England, over a 7-year period between 2003/04 and 2009/10. We enrolled 124 503 adults with type 2 diabetes. Outcome measures included admission to hospital for acute myocardial infarction (MI), stroke, heart failure or pneumonia/influenza, and death. We fitted Poisson regression models for influenza and off-season periods to estimate incidence rate ratios (IRR) for cohorts who had and had not received the vaccine. We used estimates for the summer, when influenza activity is low, to adjust for residual confounding. Results: Study participants contributed to 623 591 person-years of observation during the 7-year study period. Vaccine recipients were older and had more comorbid conditions compared with nonrecipients. After we adjusted for covariates and residual confounding, vaccination was associated with significantly lower admission rates for stroke (IRR 0.70, 95% confidence interval [CI] 0.53-0.91), heart failure (IRR 0.78, 95% CI 0.65-0.92) and pneumonia or influenza (IRR 0.85, 95% CI 0.74-0.99), as well as all-cause death (IRR 0.76, 95% CI 0.65-0.83), and a nonsignificant change for acute MI (IRR 0.81, 95% CI 0.62-1.04) during the influenza seasons. Interpretation: In this cohort of patients with type 2 diabetes, influenza vaccination was associated with reductions in rates of admission to hospital for specific cardiovascular events. Efforts should be focused on improvements in vaccine uptake in this important target group as part of comprehensive secondary prevention., The health burden caused by seasonal influenza in the general population is substantial and explains much of the excess winter mortality. (1-3) Influenza infection may accelerate acute thrombotic vascular events, [...]

For decades, transplantation has been a life-saving treatment for those fortunate enough to gain access. Nevertheless, many patients die waiting for an organ and countless more never make it onto the waitlist because of a shortage of donor organs. Concurrently, thousands of donated organs are declined for transplant each year because of concerns about poor outcomes post-transplant. The decline of any donated organ—even if medically justified—is tragic for both the donor family and potential recipients. In this Personal Viewpoint, we discuss the need for a new mindset in how we honor the gift of organ donation. We believe that the use of transplant-declined human organs in translational research has the potential to hasten breakthrough discoveries in a multitude of scientific and medical areas. More importantly, such breakthroughs will allow us to properly value every donated organ. We further discuss the many practical challenges that such research presents and offer some possible solutions based on experiences in our own research laboratories. Finally, we share our perspective on what we believe are the necessary next steps to ensure a future where every donated organ realizes its full potential to impact the lives of current and future patients.

The article features a collection of letters from readers of Evo magazine. One reader reminisces about their experience with a mid-engined car, while another shares their thoughts on the emotional impact of cars. Another reader discusses their frustration with modern car lights, and another expresses their opinion on the definition of a hot hatch. One reader finds humor in a writer's hairdresser comment, and the letter of the month recounts a memorable visit to the Porsche Experience Centre. [Extracted from the article]

This article considers minimum time optimal control problems with linear dynamics subject to state equality constraints and control inequality constraints. In the absence of state constraints, there are well-known sufficient conditions to guarantee that optimal controls are at the boundary or extreme points of the control set. With strong observability as the key tool, analogous conditions are derived for problems subject to both extrinsic and intrinsic state constraints. Understanding these geometric properties enables exact convex relaxations. The relaxation technique is used to convert a nonconvex quadratic program to a second-order cone program and a mixed integer linear program to a linear program. The relaxations accelerate numerical solution times by factors of 18 000 and 150, respectively. As such, the theorems and relaxations are seen as important tools for real-time optimization-based control.

This paper analyzes optimal control problems with linear time-varying dynamics defined on a smooth manifold in addition to mixed constraints and pure control constraints. The main contribution is the identification of sufficient conditions for the optimal controls to be non-singular, which enables exact (or lossless) convex relaxations of the control constraints. The problem is analyzed in a geometric framework using a recent maximum principle on manifolds, and it is shown that strong observability of the dual system on the cotangent space is the key condition. Two minimum time problems are analyzed and solved. A minimum fuel planetary descent problem is then analyzed and relaxed to a convex form. Convexity enables its efficient solution in less than one second without any initial guess.

ABSTRACTImpairments in macroautophagy/autophagy, which degrades dysfunctional organelles as well as long-lived and aggregate proteins, are associated with several cardiomyopathies; however, the regulation of cardiac autophagy remains insufficiently understood. In this regard, ULK1 and ULK2 are thought to play primarily redundant roles in autophagy initiation, but whether their function is developmentally determined, potentially having an impact on cardiac integrity and function remains unknown. Here, we demonstrate that perinatal loss of ULK1 or ULK2 in cardiomyocytes (cU1-KO and cU2-KO mice, respectively) enhances basal autophagy without altering autophagy machinery content while preserving cardiac function. This increased basal autophagy is dependent on the remaining ULK protein given that perinatal loss of both ULK1 and ULK2 in cU1/2-DKO mice impaired autophagy causing age-related cardiomyopathy and reduced survival. Conversely, adult loss of cardiac ULK1, but not of ULK2 (i.e., icU1-KO and icU2-KO mice, respectively), led to a rapidly developing cardiomyopathy, heart failure and early death. icU1-KO mice had impaired autophagy with robust deficits in mitochondrial respiration and ATP synthesis. Trehalose ameliorated autophagy impairments in icU1-KO hearts but did not delay cardiac dysfunction suggesting that ULK1 plays other critical, autophagy-independent, functions in the adult heart. Collectively, these results indicate that cardiac ULK1 and ULK2 are functionally redundant in the developing heart, while ULK1 assumes a more unique, prominent role in the adult heart.Abbreviations:ATG4: autophagy related 4, cysteine peptidase; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG9: autophagy related 9; ATG13: autophagy related 13; CYCS: Cytochrome C; DNM1L, dynamin 1-like; MAP1LC3A: microtubule-associated protein 1 light chain 3 alpha; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MFN2: mitofusin 2; MT-CO1: mitochondrially encoded cytochrome c oxidase I; MYH: myosin, heavy polypeptide; NBR1: NBR1 autophagy cargo receptor; NDUFA9: NADH:ubiquinone oxidoreductase subunit A9; OPA1: OPA1, mitochondrial dynamin like GTPase; PPARGC1A, peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; SDHA: succinate dehydrogenase complex, subunit A, flavoprotein (Fp); SQSTM1: sequestosome 1; ULK1: unc-51 like kinase 1; ULK2: unc-51 like kinase 2; UQCRC1: ubiquinol-cytochrome c reductase core protein 1

Dear Retro Gamer, I would like to know whether there is a convenient way to order Retro Gamer back issues in print, as there are some issues that may be [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jtcvs.2008.11.062 Byline: Kevin K. Whitehead (a), Kartik S. Sundareswaran (b), W. James Parks (c), Matthew A. Harris (a), Ajit P. Yoganathan (b), Mark A. Fogel (a) Abbreviations: BSA, body surface area; CHOA, Children's Healthcare of Atlanta; CHOP, Children's Hospital of Philadelphia; CMR, cardiac magnetic resonance imaging; IVC, inferior vena cava; LPA, left pulmonary artery; MRI, magnetic resonance imaging; RPA, right pulmonary artery; SVC, superior vena cava Abstract: Our goal was to determine flow distribution in the cavopulmonary connections of patients with and without bilateral superior venae cavae who had the Fontan procedure. No large series exists that establishes the flow distributions in Fontan patients, which would be an important resource for everyday clinical use and may affect future surgical reconstruction. Author Affiliation: (a) Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, Pa (b) Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Ga (c) Sibley Heart Center, Children's Health Care of Atlanta, Emory University School of Medicine, Atlanta, Ga Article History: Received 28 January 2008; Revised 20 October 2008; Accepted 23 November 2008 Article Note: (footnote) This work was supported in part by the National Institutes of Health BRP Grant R01 HL 67622 and by the Pediatric Heart Network Fontan cross-sectional study 5U01HL68279-03.

Heterotopic ossification is the inappropriate formation of bone in soft tissues of the body. It can manifest spontaneously in rare genetic conditions or as a response to injury, known as acquired heterotopic ossification. There are several experimental models for studying acquired heterotopic ossification from different sources of damage. However, their tenuous mechanistic relevance to the human condition, invasive and laborious nature and/or lack of amenability to chemical and genetic screens, limit their utility. To address these limitations, we developed a simple zebrafish injury model that manifests heterotopic ossification with high penetrance in response to clinically emulating injuries, as observed in human myositis ossificans traumatica. Using this model, we defined the transcriptional response to trauma, identifying differentially regulated genes. Mutant analyses revealed that an increase in the activity of the potassium channel Kcnk5b potentiates injury response, whereas loss of function of the interleukin 11 receptor paralogue (Il11ra) resulted in a drastically reduced ossification response. Based on these findings, we postulate that enhanced ionic signalling, specifically through Kcnk5b, regulates the intensity of the skeletogenic injury response, which, in part, requires immune response regulated by Il11ra.

ObjectiveKangaroo Mother Care (KMC) is a frugal innovation improving newborn health at a reduced cost compared with incubator use. KMC is widely recommended; however, in the UK, poor evidence exists on KMC, and its implementation remains inconsistent.DesignThis Systematic Review and Realist Synthesis explores the barriers and facilitators in the implementation of KMC in the UK.Data sourceOVID databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus and Google Scholar were searched.Eligibility criteriaStudies were UK based, in maternity/neonatal units, for full-term/preterm children. First screening included studies on (1) KMC, Kangaroo Care (KC) or skin-to-skin contact (SSC) or (2) Baby Friendly Initiative, Small Wonders Change Program or family-centred care if in relation to KMC/KC/SSC. Full texts were reviewed for evidence regarding KMC/KC/SSC implementation.ResultsThe paucity of KMC research in the UK did not permit a realist review. However, expanded review of available published studies on KC and SSC, used as a proxy to understand KMC implementation, demonstrated that the main barriers are the lack of training, knowledge, confidence and clear guidelines.ConclusionThe lack of KMC implementation research in the UK stands in contrast to the already well-proven benefits of KMC for stable babies in low-income contexts and highlights the need for further research, especially in sick and small newborn population. Implementation of, and research into, KC/SSC is inconsistent and of low quality. Improvements are needed to enhance staff training and parental support, and to develop guidelines to properly implement KC/SSC. It should be used as an opportunity to emphasise the focus on KMC as a potential cost-effective alternative to reduce the need for incubator use in the UK.

The aim of this study was to determine the effect of voluntary wheel running (VWR) during weight-loss on hepatic lipid and inflammatory biomarkers using a murine model. To induce obesity, male C57Bl/6 mice were fed a 60% high-fat diet (HF) for 10 weeks. At 10 weeks, weight-loss was promoted by randomizing HF-fed mice to a normal diet (ND) either with (WL + VWR) or without (WL) access to running wheels for 8 weeks. Age-matched dietary control mice were fed either a ND or HF for 18 weeks. Following weight-loss, WL + VWR had a lower body mass compared to all groups despite an average weekly caloric consumption comparable to HF mice. WL + VWR had an increased adiponectin concentration when compared to WL, but no difference between WL and WL + VWR was observed for plasma glucose and lipid biomarkers. When compared to HF, the lower hepatic total lipids in both WL and WL + VWR were associated with increased pAMPK:AMPK and reduced pACC-1:ACC-1 ratios. When compared to WL, WL + VWR resulted in lower hepatic cholesterol and trended to lower hepatic triglyceride. In both WL and WL + VWR, pNF-κB p65:NF-κB p65 ratio was lower than HF and comparable to ND. TGFβ1 and BAMBI protein levels were evaluated as biomarkers for hepatic fibrosis. No differences in TGFβ1 was observed between groups; however, WL and WL + VWR had BAMBI protein levels comparable to ND. Overall, the addition of voluntary exercise resulted in greater weight-loss and improvements in hepatic cholesterol and triglyceride levels; however, limited improvements in hepatic inflammation were observed when compared to weight-loss by diet alone.

The Drill Cover system was developed as a low-cost alternative to conventional surgical drills with specific applicability to low- and middle-income countries. However, the system may also be useful for the sterile placement of traction pins in the emergency department of high-income country hospitals. In September 2019, a US-based Level-1 trauma center began using the Drill Cover system to apply skeletal traction pins in patients with femoral shaft fractures. With these data, we performed a retrospective interrupted time series study to determine if the Drill Cover system was noninferior to conventional surgical drills in terms of infections at the traction pin site. The study included 205 adult patients with femoral shaft fractures initially placed in skeletal traction using a conventional surgical drill (n = 150, preintervention group) or the Drill Cover system (n = 55, postintervention group). The primary outcome was an infection at the site of skeletal traction pin placement that required surgery or antibiotics, which was compared between groups using a noninferiority test with a 1-sided alpha of 0.05 and a noninferiority margin of 3%. No infections at the site of skeletal traction pin placement were found in either the preintervention or the postintervention group (difference, 0%; 95% confidence interval: 0.0%–1.4%; noninferiority Pvalue < 0.01). The results suggest that the Drill Cover system was noninferior to conventional surgical drills regarding infections at the site of skeletal traction pins. The Drill Cover system may be a safe alternative to the more expensive surgical drills for skeletal traction pin placement in the emergency room environment.

The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin’s importance for illuminating vertebrate biology and diversity in the genomic era.

The diagnosis of malignant melanoma is based on clinical grounds and a properly performed biopsy, preferably excision, so that the type of melanoma and the thickness can be assessed by methods described by Clark and Breslow. These facilitate clinical and pathologic staging. Excisions with conservative margins for thin lesions (less than 1.0 mm in thickness) and more extensive margins for thicker lesions are appropriate. The issue of elective lymph node dissection is controversial. Most authors agree it is not indicated for lesions less than 1.0 mm thick and may offer little advantage for lesions greater than 4.0 mm thick. Several retrospective studies show a survival advantage in patients with 'intermediate' thickness melanomas who may have occult nodal metastases. However, there are prospective randomized clinical trials supporting the concept that positive lymph nodes are a manifestation of systemic disease, and survival is equivalent in patients who have subsequent therapeutic lymph node dissections. A procedure using intraoperative lymphatic mapping and selective lymphadenectomy may identify those patients who are likely to benefit from lymphadenectomy.

Background. Melanoma vaccine treatment appears to slow the progression of melanoma in some patients, particularly in patients in whom it stimulates cellular antimelanoma immune responses. The relationship of vaccine-induced antibody responses to clinical outcome is less clear. The purpose of this study was to investigate the clinical relevance of antibody responses to melanoma vaccine immunization. Methods. Eighty-two evaluable patients with surgically resected American Joint Committee on Cancer Stage III malignant melanoma were immunized to a partially purified, polyvalent, melanoma antigen vaccine. Antimelanoma antibodies were measured by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis before vaccine treatment and 1 week after the fourth immunization. Results. Vaccine treatment induced or augmented antibody responses to melanoma in 32 (39%) of the patients. The antibodies were directed to one or more antigens of 38-43, 75, 110, 150 and/or 210 kDs, which previously have been shown to be expressed preferentially in cultured human melanoma cells. The median disease free survival of patients with a vaccine-induced antibody response to one or more of these antigens was 5.4 years compared with 1.4 years for nonresponders (P = 0.06), and 5-year overall survival was 71% compared with 44%, respectively (P = Conclusions. The antibody response to vaccine treatment is an immune marker of vaccine activity that appears to be predictive of a later reduction in the recurrence of melanoma and is unrelated to the vaccine's ability to induce cellular immune responses. This finding suggests that vaccine treatment may be effective in slowing the progression of melanoma in some patients and that the protective effect is mediated partly by vaccineinduced antimelanoma antibodies.

KEYING FOR LARGE PUBLIC TRANSPORTATION ENTITIES REQUIRES A LONGER look to the future and a longer look by the consultant to help guide the customer into good decisions for that [...]

The authors investigated whether there was a relationship between the induction of a delayed-type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease-free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients. Cancer 1992; 69:1157-1164.

KEYING FOR LARGE PUBLIC TRANSPORTATION ENTITIES REQUIRES A LONGER look to the future and a longer look by the consultant to help guide the customer into good decisions for that [...]

As more women are screened for early breast cancer with mammography, more breast cancers are being detected in their earliest stages. Also being detected, however, are suspicious-looking lesions that require biopsy for clarification. Many of these lesions are too small to be felt, however, which poses problems for the practitioner attempting to sample the suspect tissue with a biopsy needle. Several methods exist for trying to locate the lesion during the actual biopsy procedure, including ultrasonography and the use of X-rays to guide the needle. Another method is stereotactic localization. In this procedure, computer analysis is performed on X-ray images to provide precise coordinates of the suspicious lesion in three dimensions. The physician then guides the biopsy needle to the point defined by the numbers without any direct visualization. A study was conducted to evaluate the effectiveness of this method. A total of 300 stereotaxic biopsy procedures were performed on consecutive patients with suspicious but nonpalpable breast lesions. Of these, 151 were judged to be normal on the basis of the biopsy and were followed-up only by subsequent mammography. Of the remaining 149, 68 were judged either suspicious or malignant; this evaluation was confirmed by histological examination of the tissue removed at surgery in all cases. Sixty-five lesions thought to be benign on the basis of the needle biopsy were also removed surgically, and these too proved to be benign in all cases. These most important findings of this study were that, so far, no malignant lesion was missed by the stereotaxic biopsy technique. (Consumer Summary produced by Reliance Medical Information, Inc.)

There are three RhoGDIs in mammalian cells, which were initially defined as negative regulators of Rho family small GTPases. However, it is now accepted that RhoGDIs not only maintain small GTPases in their inactive GDP-bound form but also act as chaperones for small GTPases, targeting them to specific intracellular membranes and protecting them from degradation. Studies to date with RhoGDIs have usually focused on the interactions between the “typical” or “classical” small GTPases, such as the Rho, Rac, and Cdc42 subfamily members, and either the widely expressed RhoGDI-1 or the hematopoietic-specific RhoGDI-2. Less is known about the third member of the family, RhoGDI-3 and its interacting partners. RhoGDI-3 has a unique N-terminal extension and is found to localize in both the cytoplasm and the Golgi. RhoGDI-3 has been shown to target RhoB and RhoG to endomembranes. In order to facilitate a more thorough understanding of RhoGDI function, we undertook a systematic study to determine all possible Rho family small GTPases that interact with the RhoGDIs. RhoGDI-1 and RhoGDI-2 were found to have relatively restricted activity, mainly binding members of the Rho and Rac subfamilies. RhoGDI-3 displayed wider specificity, interacting with the members of Rho, Rac, and Cdc42 subfamilies but also forming complexes with “atypical” small Rho GTPases such as Wrch2/RhoV, Rnd2, Miro2, and RhoH. Levels of RhoA, RhoB, RhoC, Rac1, RhoH, and Wrch2/RhoV bound to GTP were found to decrease following coexpression with RhoGDI-3, confirming its role as a negative regulator of these small Rho GTPases.

Broadband dielectric spectroscopy, rheology, and nuclear magnetic resonance spectroscopy are employed to study molecular dynamics in a nanoparticle organic hybrid material (NOHMs) system comprising 20 wt % silica nanoparticles ionically bonded to a polyethylenimine canopy. By comparing the neat polymer (used as a canopy) to the derivative NOHMs, we find that timescales characterizing segmental dynamics in the NOHM are identical to those for the neat polymer. Detailed analysis of the carbon-spin lattice relaxation times yields mechanistic insights into localized and collective dynamics, in quantitative agreement with dielectric results. Interestingly, the NOHMs retain liquid-like characteristics unlike conventional polymer nanocomposites but exhibit higher viscosity due to additional contributions from tethered polymer chains and mesoscopic structuring. These findings demonstrate the potential of achieving unique and desired material properties viaNOHMs by an informed choice of the canopy material.

Frugal innovation (FI), which has gained traction in various sectors, is loosely defined as developing quality solutions in a resource-constrained environment that are affordable to low-income consumers. However, with its popularity, multiple and diverse definitions have emerged that often lack a theoretical foundation. This has led to a convoluted conceptualisation that hinders research and adoption in practice. Despite this plethora of perspectives and definitions, scholars do agree that there is a need for a unified definition. This critical review across the management, entrepreneurship, business and organisation studies literatures explores the multiple definitions of FI that have appeared in the last two decades and seeks to examine the commonalities and differences. One definition is supported by a theoretical underpinning, and main themes include affordability, adaptability, resource scarcity, accessibility and sustainability, however, there remains significant ambiguity around what constitutes an FI. Defining FI as a concept should not deter from focusing on its core aim and identifying an FI may be best achieved by comparing it to an incumbent alternative, rather than against an ill-defined concept. There is merit in developing a common understanding of FI to support strategies for its successful acceptance and diffusion globally.

With over two decades of evidence available including from randomised clinical trials, we explore whether the use of low-cost mosquito net mesh for inguinal hernia repair, common practice only in low-income and middle-income countries, represents a double standard in surgical care. We explore the clinical evidence, biomechanical properties and sterilisation requirements for mosquito net mesh for hernia repair and discuss the rationale for its use routinely in all settings, including in high-income settings. Considering that mosquito net mesh is as effective and safe as commercial mesh, and also with features that more closely resemble normal abdominal wall tissue, there is a strong case for its use in all settings, not just low-income and middle-income countries. In the healthcare sector specifically, either innovations should be acceptable for all contexts, or none at all. If such a double standard exists and worse, persists, it raises serious questions about the ethics of promoting healthcare innovations in some but not all contexts in terms of risks to health outcomes, equitable access, and barriers to learning.