Cigarette smoking increases the development of intimal hyperplasia after vascular injury

Purpose: Our purpose was to determine whether exposure to cigarette smoke increases the development of intimal hyperplasia (IH) after vascular injury.Methods: Sixteen adult male Sprague-Dawley rats underwent standardized balloon catheter injury of the left common carotid artery. For 4 weeks before and 4 weeks after injury, animals in the experimental group (n=8) were exposed to cigarette smoke with an automated vacuum pump device. Animals in the control group (n=8) were restrained in the smoking device for an identical amount of time and underwent arterial injury at 4 weeks but were not exposed to cigarette smoke. Carotid arteries were perfusion-fixed in vivo, prepared as histologic cross sections, and stained for elastin. IH was measured by planimetry and is reported both as the absolute area of IH and as the ratio (IH/IEL) of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (expressed as a percent).Results: The absolute area of IH was 2.09±0.34 for the experimental group compared with 0.94±0.25 for the control group; mean IH/IEL was 43.7%±7.1% for the experimental group versus 17.7%±4.7% for the control group (p<0.05, two-tailed unpaired t test).Conclusions: Inhalation of cigarette smoke increases the development of intimal hyperplasia in a rat model of balloon catheter arterial injury

Surgical results: A justification of the surgeon selection process for the ACAS trial

AbstractPurpose: The selection of surgeons to participate in a prospective randomized trial comparing the efficacy of a surgical method with medical management is critically important because it will have a direct impact on the outcome of the study and the future use of the operation. We report the success of the method used for selecting surgeons who participated in the Asymptomatic Carotid Atherosclerosis Study (ACAS) by examining the surgical morbidity and mortality rates and the outcome of the study.Methods: A Surgical Management Committee established criteria for auditing surgeons who wished to participate in the study. The parameters included a minimum performance of at least 12 carotid endarterectomies (CEA) per year and an audit of each surgeon's last 50 consecutive CEAs with required documentation of a combined neurologic morbidity and mortality rate of <3.0% for asymptomatic patients and <5.0% for all indications including symptomatic patients.Results: As of February 1991, 164 surgeons from 48 medical centers applied for ACAS participation. One hundred seventeen were approved, and their aggregate experience of 5641 operations yielded a combined neurologic morbidity and mortality rate of 2.3% for asymptomatic and symptomatic patients combined. The morbidity and mortality rate for CEA on asymptomatic patients was 1.7%. These surgeons, plus those recruited after February 1991, became investigators in the ACAS trial and were responsible for the surgical care of 825 patients who were randomized to the surgical arm. Seven hundred twenty-four patients actually underwent CEA. One patient (0.14%) died and ten patients (1.38%) had strokes within the 30-day perioperative interval, for a combined stroke or death incidence of 1.52%. The 5-year stroke event rate in the surgical group (including perioperative morbidity and mortality rates) was 5.1%, compared with 11% of patients treated medically, yielding a relative risk reduction of 53% in favor of surgery ( p =0.004).Conclusions: A method for selecting surgeons for participation in the ACAS trial was successful in providing low perioperative morbidity and mortality rates. This materially influenced the outcome of the study in favor of CEA. (J VASC SURG 1996;23:323-8.

The modern pollen-vegetation relationship of a tropical forest-savannah mosaic landscape, Ghana, West Africa

Transitions between forest and savannah vegetation types in fossil pollen records are often poorly understood due to over-production by taxa such as Poaceae and a lack of modern pollen-vegetation studies. Here, modern pollen assemblages from within a forest-savannah transition in West Africa are presented and compared, their characteristic taxa discussed, and implications for the fossil record considered. Fifteen artificial pollen traps were deployed for 1 year, to collect pollen rain from three vegetation plots within the forest-savannah transition in Ghana. High percentages of Poaceae and Melastomataceae/Combretaceae were recorded in all three plots. Erythrophleum suaveolens characterised the forest plot, Manilkara obovata the transition plot and Terminalia the savannah plot. The results indicate that Poaceae pollen influx rates provide the best representation of the forest-savannah gradient, and that a Poaceae abundance of >40% should be considered as indicative of savannah-type vegetation in the fossil record

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Arabidopsis thaliana POLYOL/MONOSACCHARIDE TRANSPORTERS 1 and 2: fructose and xylitol/H+ symporters in pollen and young xylem cells

The genome of Arabidopsis thaliana contains six genes, AtPMT1 to AtPMT6 (Arabidopsis thaliana POLYOL/MONOSACCHARIDE TRANSPORTER 1–6), which form a distinct subfamily within the large family of more than 50 monosaccharide transporter-like (MST-like) genes. So far, only AtPMT5 [formerly named AtPLT5 (At3g18830)] has been characterized and was shown to be a plasma membrane-localized H+-symporter with broad substrate specificity. The characterization of AtPMT1 (At2g16120) and AtPMT2 (At2g16130), two other, almost identical, members of this transporter subfamily, are presented here. Expression of the AtPMT1 and AtPMT2 cDNAs in baker's yeast (Saccharomyces cerevisiae) revealed that these proteins catalyse the energy-dependent, high-capacity transport of fructose and xylitol, and the transport of several other compounds with lower rates. Expression of their cRNAs in Xenopus laevis oocytes showed that both proteins are voltage-dependent and catalyse the symport of their substrates with protons. Fusions of AtPMT1 or AtPMT2 with the green fluorescent protein (GFP) localized to Arabidopsis plasma membranes. Analyses of reporter genes performed with AtPMT1 or AtPMT2 promoter sequences showed expression in mature (AtPMT2) or germinating (AtPMT1) pollen grains, as well as in growing pollen tubes, hydathodes, and young xylem cells (both genes). The expression was confirmed with an anti-AtPMT1/AtPMT2 antiserum (αAtPMT1/2) raised against peptides conserved in AtPMT1 and AtPMT2. The physiological roles of the proteins are discussed and related to plant cell wall modifications

Cornucopia: Temporal safety for CHERI heaps

Use-after-free violations of temporal memory safety continue to plague software systems, underpinning many high-impact exploits. The CHERI capability system shows great promise in achieving C and C++ language spatial memory safety, preventing out-of-bounds accesses. Enforcing language-level temporal safety on CHERI requires capability revocation, traditionally achieved either via table lookups (avoided for performance in the CHERI design) or by identifying capabilities in memory to revoke them (similar to a garbage-collector sweep). CHERIvoke, a prior feasibility study, suggested that CHERI’s tagged capabilities could make this latter strategy viable, but modeled only architectural limits and did not consider the full implementation or evaluation of the approach. Cornucopia is a lightweight capability revocation system for CHERI that implements non-probabilistic C/C++ temporal memory safety for standard heap allocations. It extends the CheriBSD virtual-memory subsystem to track capability flow through memory and provides a concurrent kernel-resident revocation service that is amenable to multi-processor and hardware acceleration. We demonstrate an average overhead of less than 2% and a worst-case of 8.9% for concurrent revocation on compatible SPEC CPU2006 benchmarks on a multi-core CHERI CPU on FPGA, and we validate Cornucopia against the Juliet test suite’s corpus of temporally unsafe programs. We test its compatibility with a large corpus of C programs by using a revoking allocator as the system allocator while booting multi-user CheriBSD. Cornucopia is a viable strategy for always-on temporal heap memory safety, suitable for production environments.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (“CTSRD”) and HR0011-18-C-0016 (“ECATS”). We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ABP Grant (EP/P020011/1), the ERC ELVER Advanced Grant (789108), the Gates Cambridge Trust, Arm Limited, HP Enterprise, and Google, Inc

The impact of transcranial direct current stimulation on inhibitory control in young adults

In recent years, many important discoveries have been made to challenge current policy, guidelines, and practice regarding how best to prevent stroke associated with atherosclerotic stenosis of the origin of the internal carotid artery. TheUnited States Center forMedicare andMedicaid Services (CMS), for instance, is calling for expert advice as to whether its current policies should be modified. Using a thorough review of literature, 41 leading academic stroke-prevention clinicians from the United States and other countries, have united to advise CMS not to extend current reimbursement indications for carotid angioplasty/stenting (CAS) to patients with asymptomatic carotid stenosis or to patients with symptomatic carotid stenosis considered to be at low or standard risk from carotid endarterectomy (CEA). It was concluded that such expansion of reimbursement indications would have disastrous health and economic consequences for the United States and any other country that may follow such inappropriate action. This was an international effort because the experts to best advise CMS are relatively few and scattered around the world. In addition, US health policy, practice, and research have tended to have strong influences on other countries. © 2012 The Authors. Published by Wiley Periodicals, Inc

Focusing on fast food restaurants alone underestimates the relationship between neighborhood deprivation and exposure to fast food in a large rural area

<p>Abstract</p> <p>Background</p> <p>Individuals and families are relying more on food prepared outside the home as a source for at-home and away-from-home consumption. Restricting the estimation of fast-food access to fast-food restaurants alone may underestimate potential spatial access to fast food.</p> <p>Methods</p> <p>The study used data from the 2006 Brazos Valley Food Environment Project (BVFEP) and the 2000 U.S. Census Summary File 3 for six rural counties in the Texas Brazos Valley region. BVFEP ground-truthed data included identification and geocoding of all fast-food restaurants, convenience stores, supermarkets, and grocery stores in study area and on-site assessment of the availability and variety of fast-food lunch/dinner entrées and side dishes. Network distance was calculated from the population-weighted centroid of each census block group to all retail locations that marketed fast food (<it>n </it>= 205 fast-food opportunities).</p> <p>Results</p> <p>Spatial access to fast-food opportunities (FFO) was significantly better than to traditional fast-food restaurants (FFR). The median distance to the nearest FFO was 2.7 miles, compared with 4.5 miles to the nearest FFR. Residents of high deprivation neighborhoods had better spatial access to a variety of healthier fast-food entrée and side dish options than residents of low deprivation neighborhoods.</p> <p>Conclusions</p> <p>Our analyses revealed that identifying fast-food restaurants as the sole source of fast-food entrées and side dishes underestimated neighborhood exposure to fast food, in terms of both neighborhood proximity and coverage. Potential interventions must consider all retail opportunities for fast food, and not just traditional FFR.</p

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports