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Cerebral oedema is associated with morbidity and mortality after traumatic brain injury (TBI)1. Noradrenaline levels are increased after TBI2–4, and the amplitude of the increase in noradrenaline predicts both the extent of injury5and the likelihood of mortality6. Glymphatic impairment is both a feature of and a contributor to brain injury7,8, but its relationship with the injury-associated surge in noradrenaline is unclear. Here we report that acute post-traumatic oedema results from a suppression of glymphatic and lymphatic fluid flow that occurs in response to excessive systemic release of noradrenaline. This post-TBI adrenergic storm was associated with reduced contractility of cervical lymphatic vessels, consistent with diminished return of glymphatic and lymphatic fluid to the systemic circulation. Accordingly, pan-adrenergic receptor inhibition normalized central venous pressure and partly restored glymphatic and cervical lymphatic flow in a mouse model of TBI, and these actions led to substantially reduced brain oedema and improved functional outcomes. Furthermore, post-traumatic inhibition of adrenergic signalling boosted lymphatic export of cellular debris from the traumatic lesion, substantially reducing secondary inflammation and accumulation of phosphorylated tau. These observations suggest that targeting the noradrenergic control of central glymphatic flow may offer a therapeutic approach for treating acute TBI.

Author Steven Goldman reflects on the lessons he learned from his son Theo during their car rides to and from school. Theo, who has mild dyslexia, talked about what school was like from his point of view. His perspectives helped Goldman become a better teacher. [ABSTRACT FROM AUTHOR]

SEVERAL METHODS EXIST for selecting the MOSFETs required in dc-dc synchronous buck converters. These techniques generally target selection for highest efficiency or focus on determining the losses involved in the [...]

OBJECTIVE--This study investigated the hypothesis that baseline calcified coronary atherosclerosis may determine cardiovascular disease events in response to intensive glycemic control within the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS--At baseline, 301 type 2 diabetic participants in the VADT, a randomized trial comparing the effects of intensive versus standard glucose lowering on cardiovascular events, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular end points. RESULTS--During a median follow-up duration of 5.2 years, 89 cardiovascular events occurred. Although intensive glucose-lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC, as indicated by significant P values for treatment by log(CAC + 1) interaction terms in unadjusted and multivariable-adjusted models (0.01 and 0.03, respectively). Multivariable-adjusted hazard ratios (HRs) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories: those above and below an Agatston score of 100. Among those randomized to intensive treatment, for the subgroup with CAC >100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC ≤ 100 had an event. The multivariable HR for intensive treatment for those with CAC >100 was 0.74 (95% CI 0.46-1.20; P = 0.21), while for the subgroup with CAC ≤ 100, the corresponding HR was 0.08 (0.008-0.77; P = 0.03), with event rates of 39 and 4 per 1,000 person-years, respectively. CONCLUSIONS--These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis., Despite a wealth of epidemiologic data indicating that poor glycemic control is associated with increased risk for subsequent cardiovascular disease (CVD) events (1-4), trials of glucose-lowering therapy have not reduced [...]

A poem "The Copenhagen Interpretation" by Steven Goldman, is presented. First Line: I believe; Last Line: the universe.

Several states have laws allowing attorney's fees to be awarded in cases in which an insured sues an insurance company for denial of coverage. The US Court of Appeal for the 2d Circuit decided in American National Fire Insurance Co. v. Kenealy that marine insurance companies did not fall under such laws. However, the 11th Circuit, in All Underwriters v. Weisberg reached the opposite conclusion, confusing the issue.

Giovanni Ribisi has given some memorable screen preformances that have earned him comparisons to Marlon Brando and Robert De Niro. His life and career are profiled.

The author discusses federal court rulings which hold that when an insurance broker places insurance coverage in the global marine insurance market, the broker acts as an agent of the insured.

The authors discuss how the brain eliminates proteins and other wastes and their role in causing the cognitive problems encountered in neurodegenerative disease. They say that brain cells process their own wastes during sleep through perivascular spaces. They note that lack of sleep can contribute to the development of neurodegenerative diseases such as dementia, Alzheimer's disease, and mental illness.

Background: Empirical scores, computerized ST-segment measurements, and equations have been proposed as tools for improving the diagnostic performance of the exercise test. Objective: To compare the diagnostic utility of these scores, measurements, and equations with that of visual ST-segment measurements in patients with reduced workup bias. Design: Prospective analysis. Setting: 12 university-affiliated Veterans Affairs Medical Centers. Patients: 814 consecutive patients who presented with angina pectoris and agreed to undergo both exercise testing and coronary angiography. Measurements: Digital electrocardiographic recorders and angiographic calipers were used for testing at each site, and test results were sent to core laboratories. Results: Although 25% of patients had previously had testing, workup bias was reduced, as shown by comparison with a pilot study group. This reduction resulted in a sensitivity of 45% and a specificity of 85% for visual analysis. Computerized measurements and visual analysis had similar diagnostic power. Equations incorporating nonelectrocardiographic variables and either visual or computerized ST-segment measurement had similar discrimination and were superior to single ST-segment measurements. These equations correctly classified 5 more patients of every 100 tested (areas under the receiver-operating characteristic curve, 0.80 for equations and 0.68 for visual analysis; P [is less than] 0.001) in this population with a 50% prevalence of disease. Conclusions: Standard exercise tests had lower sensitivity but higher specificity in this population with reduced work-up bias than in previous studies. Computerized ST-segment measurements were similar to visual ST-segment measurements made by cardiologists. Considering more than ST-segment measurements can enhance the diagnostic power of the exercise test., The electrocardiographic exercise test can still be useful if other measurements besides ST-segment measurements are made. Elevation or depression of the ST segment on a ECG during exercise can reveal reduced blood flow to the heart. Researchers measured heart rate, blood pressure and other hemodynamic variables as well as ST-segment changes in 814 patients who had chest pain. The patients then had coronary angiography, a technique to detect coronary artery disease. The addition of other measurements reduced the ability of the test to detect coronary artery disease but increased its ability to rule out the disease.

Corporations need to establish crisis management, communications and recovery plans that address the immediate and long-term effects of disastrous events. Such plans can safeguard trust and credibility and prevent economic and intrinsic losses. Risk managers need to conduct thorough business analyses to determine how a disastrous event will affect business operations, services, deliveries, facilities and other processes., Mr. Risk Manager was in an especially good mood one recent Monday morning as he drove to work at the Acme Corporation in Anytown, U.S.A. The Friday before, he had [...]

In 1992, based on extensive review of the literature, we concluded that in patients with mechanical prosthetic heart valves,[1] (1) long-term (permanent) therapy with oral anticoagulants offers the most consistent [...]

Evidence is strong that antithrombotic therapy shows a beneficial effect in reducing the frequency of saphenous vein bypass graft closure. Since our review of the subject in 1992,[1] new information [...]

Rule 9(h) of the Federal Rules of Civil Procedure grants underwriters of marine insurance policies the right to initiate actions seeking a declaratory judgement in federal court. No other type of insurer has this option of avoiding a jury trial while still bringing disputes before a court. The advantages of avoiding a jury and hearing maritime cases in federal courts are discussed.

Virtuality has emerged as one of the most compelling new business strategies in the arena of global competition for high value-added goods and services. The competitive environment that a growing [...]

The impact of technological and innovations and organization change on the competitiveness of US manufacturing firms was investigated in relation with developments in Japan. Two factors influencing the adoption of technological innovations and appropriation of technical resources were managerial responsibility over technical resources and their application and management's responsiveness to innovations in manufacturing processes. With the adoption of new technology, the manufacturing firm can then evolve into a highly-responsive organization which can readily enter emerging niches.

SAPHENOUS VEIN BYPASS GRAFTS Over one half of the randomized prospective studies of anticoagulants or antiplatelet agents on saphenous vein graft closure have shown a beneficial effect of therapy[1-9] (Table [...]

Recommendations of the 1986[1] and 1989[2] consensus committee were that patients with mechanical prosthetic heart valves be treated with long-term warfarin, at a dose sufficient to prolong the prothrombin time [...]

The Ball Aptitude Battery, a multiple ability test battery, was administered to 121 young adults at age 18 and readministered at age 22. Test-retest correlations for individual tests ranged from .30 to .90, the highest coefficients ([r.sub.tt]s above .75) being observed on tests measuring (a) vocabulary, (b) hand and arm strength, (c) spatial ability, and (d) detail perception. Significant growth in ability (positive change scores) was observed on tests measuring (a) vocabulary, (b) reasoning ability, (c) detail perception, (d) spatial ability, and (e) hand and arm strength. Significant decline was observed on tests measuring finger dexterity. The test battery's factor structure remained relatively stable over the 4 years. Test profiles were largely stable over time with respect to rank order of scores. Gender, ethnicity, and socioeconomic status had only slight influence on ability change.

Academy Award winning actor Connery, who starred in James Bond films and many others, is not considered as intense as he once was. He is highly respected among directors. The actor discusses his career and fame.

After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function. In this model, after treatment for 3 weeks, it appears that the major benefit from angiotensin-converting enzyme inhibition is due to improvements in organ function resulting from changes in loading conditions, whereas muscle function remains compromised. (Am J Cardiol 1991;68:26D-34D)

A common problem in premature infants is respiratory distress syndrome (RDS), which develops due to the inability of the immature lungs to produce surfactant, a fatty detergent that lines the inner surface of lungs and is required for normal lung function. Although the survival of infants with RDS has improved due to the use of mechanical ventilation, many go on to develop bronchopulmonary dysplasia (BPD), abnormal tissues in the lungs and airways. Early versions of synthetic surfactant were not very effective in treating RDS, but new formulations have been devised, and better techniques for its application to the airways have been developed. The effectiveness of a single dose of a synthetic surfactant, Exosurf Neonatal, given on a prophylactic basis to over 400 premature newborns at risk for RDS was compared with that of placebo treatment. The surfactant was administered soon after birth. There were 40 percent fewer deaths in the surfactant-treated group, and improved survival was maintained through one year of age. Although there were fewer deaths attributable to RDS, the incidence of BPD among survivors did not differ between groups. The incidence of several complications, including two lung problems and apnea (temporary absence of breathing) of prematurity was also decreased in the surfactant-treated group. (Consumer Summary produced by Reliance Medical Information, Inc.)

Supplemental Digital Content is available in the text.Saphenous vein grafts (SVGs) remain the most frequently used conduits in coronary artery bypass graft surgery (CABG). Despite advances in surgical techniques and pharmacotherapy, SVG failure rates remain high, often leading to repeat coronary revascularization. The no-touch SVG harvesting technique (minimal graft manipulation with preservation of vasa vasorum and nerves) reduces the risk of SVG failure, whereas the effect of the off-pump technique on SVG patency remains unclear. Use of buffered storage solutions, intraoperative graft flow measurement, careful selection of the target vessels, and physiological assessment of the native coronary circulation before CABG may also reduce the incidence of SVG failure. Perioperative aspirin and high-intensity statin administration are the cornerstones of secondary prevention after CABG. Dual antiplatelet therapy is recommended for off-pump CABG and in patients with a recent acute coronary syndrome. Intermediate (30%–60%) SVG stenoses often progress rapidly. Stenting of intermediate SVG stenoses failed to improve outcomes; hence, treatment focuses on strict control of coronary artery disease risk factors. Redo CABG is associated with higher perioperative mortality compared with percutaneous coronary intervention (PCI); hence, the latter is preferred for most patients requiring repeat revascularization after CABG. SVG PCI is limited by high rates of no-reflow and a high incidence of restenosis during follow-up. Drug-eluting and bare metal stents provide similar long-term outcomes in SVG PCI. Embolic protection devices reduce no-reflow and should be used when feasible. PCI of the corresponding native coronary artery is associated with better short- and long-term outcomes and is preferred over SVG PCI, if technically feasible.

EXECUTIVE SUMMARY * OUTSOURCING IS REVOLUTIONIZING the way business is being conducted around the world, and that means CPAs will have to rethink how they establish the value of a [...]

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters—preferably in vivo—plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical and functional barriers that promote arrhythmias in these patients. Propagation of VT in a reentrant circuit depends on the presence of excitable myocardium and the refractoriness of the circuit. We hypothesize that myocardial refractoriness can be modulated surgically in a model of HFrEF, leading to decreased susceptibility to VT.Male Sprague-Dawley rats were infarcted via permanent left coronary artery ligation. At 3 weeks post-infarction, engineered grafts composed of human dermal fibroblasts cultured into a polyglactin-910 biomaterial were implanted onto the epicardium to cover the area of infarction. Three weeks post-graft treatment, all rats underwent a terminal electrophysiologic study to compare monophasic action potential electroanatomic maps and susceptibility to inducible monomorphic VT.HFrEF rats (n=29) demonstrated a longer (p=0.0191) ventricular effective refractory period (ERP) and a greater (p=0.0394) VT inducibility compared with sham (n=7). HFrEF rats treated with the graft (n=12) exhibited no change in capture threshold (p=0.3220), but had a longer ventricular ERP (p=0.0029) compared with HFrEF. No statistically significant change in VT incidence was found between HFrEF rats treated with the graft and untreated HFrEF rats (p=0.0834).Surgical deployment of a fibroblast-containing biomaterial in a rodent ischemic cardiomyopathy model prolonged ventricular ERP as measured by programmed electrical stimulation. This hypothesis-generating study warrants additional studies to further characterize the antiarrhythmic or proarrhythmic effects of this novel surgical therapy.

The cellular neurobiology of schizophrenia remains poorly understood. We discuss neuroimaging studies, pathological findings, and experimental work supporting the idea that glial cells might contribute to the development of schizophrenia. Experimental studies suggest that abnormalities in the differentiation competence of glial progenitor cells lead to failure in the morphological and functional maturation of oligodendrocytes and astrocytes. We propose that immune activation of microglial cells during development, superimposed upon genetic risk factors, could contribute to defective differentiation competence of glial progenitor cells. The resulting hypomyelination and disrupted white matter integrity might contribute to transmission desynchronisation and dysconnectivity, whereas the failure of astrocytic differentiation results in abnormal glial coverage and support of synapses. The delayed and deficient maturation of astrocytes might, in parallel, lead to disruption of glutamatergic, potassium, and neuromodulatory homoeostasis, resulting in dysregulated synaptic transmission. By highlighting a role for glial cells in schizophrenia, these studies potentially point to new mechanisms for disease modification.

Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.

Byline: Steven L. Goldman, Roger N. Nagel This paper explores the impacts of technological innovations and organizational innovations on the competitiveness of manufacturing enterprises, in a US context, but with reference to developments in Japan. The adoption of technological innovations and the utilization of technical resources are seen not as objective processes, but as part of managerial decision-making based on management's value systems and agendas. The next stage in the development of manufacturing industry is seen as the emergence of the highly-responsive and 'agile' manufacturing enterprise, sometimes taking the form of 'virtual companies' to exploit transient or niche markets as they emerge. The key to this agility in a manufacturing enterprise is a more flexible approach to inter-firm cooperation, and the development of the creative skills of the management and the workforce.

The naked mole rat (NMR) is the longest-lived rodent, resistant to multiple age-related diseases including neurodegeneration. However, the mechanisms underlying the NMR’s resistance to neurodegenerative diseases remain elusive. Here, we isolated oligodendrocyte progenitor cells (OPCs) from NMRs and compared their transcriptome with that of other mammals. Extracellular matrix (ECM) genes best distinguish OPCs of long- and short-lived species. Notably, expression levels of CD44, an ECM-binding protein that has been suggested to contribute to NMR longevity by mediating the effect of hyaluronan (HA), are not only high in OPCs of long-lived species but also positively correlate with longevity in multiple cell types/tissues. We found that CD44 localizes to the endoplasmic reticulum (ER) and enhances basal ATF6 activity. CD44 modifies proteome and membrane properties of the ER and enhances ER stress resistance in a manner dependent on unfolded protein response regulators without the requirement of HA. HA-independent role of CD44 in proteostasis regulation may contribute to mammalian longevity.

In Lost Girls, the author of From Hell and V for Vendetta unites the heroines of three of the most popular works of children's fiction and re-imagines their surreal adventures [...]

Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder caused by mutation in the proteolipid protein‐1(PLP1) gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination, associated in most cases with early neurological dysfunction, progressive deterioration, and ultimately death. PMD may present as a connatal, classic and transitional forms, or as the less severe spastic paraplegia type 2 and PLP‐null phenotypes. These disorders are most often associated with duplications of the PLP1gene, but can also be caused by coding and noncoding point mutations as well as full or partial deletion of the gene. A number of genetically‐distinct but phenotypically‐similar disorders of hypomyelination exist which, like PMD, lack any effective therapy. Yet as relatively pure CNS hypomyelinating disorders, with limited involvement of the PNS and relatively little attendant neuronal pathology, PMD and similar hypomyelinating disorders are attractive therapeutic targets for neural stem cell and glial progenitor cell transplantation, efforts at which are now underway in a number of research centers. StemCells2017;35:311–315

Coronary artery bypass surgery is performed to bypass blocked or narrowed coronary arteries and provide new routes for blood to reach the heart; it is done to prevent angina (chest pain) and heart attacks. One of the major complications that may follow coronary artery bypass surgery is a graft occlusion, blockage of a newly routed blood vessel. Up to 15 percent of these grafts occlude one to two weeks after surgery and up to 30 percent occlude within the first year. After one year the incidence of occlusion is reduced to about two to four percent. This study has retrospectively examined the results of thirteen clinical trials with patients who underwent coronary artery bypass surgery and were subsequently treated with antiplatelet or anticoagulant drugs to prevent occlusions. Only randomized trials that used control groups were included. Data were compiled from these different, independently conducted studies and evaluated using meta-analysis, a statistical method that addresses a single question using the combined results of several independent studies. Meta-analysis is a useful tool for evaluating the many research studies that have been done on a single topic; its goal is to reach an objective conclusion concerning the meaning of the research literature available. The statistical analysis showed that active post-surgical treatment of patients with antiplatelet or anticoagulant drugs was useful. The incidence of graft occlusion after coronary artery bypass surgery was reduced in patients treated with antiplatelet or anticoagulant drugs. Also, commencement of therapy soon after surgery was beneficial. (Consumer Summary produced by Reliance Medical Information, Inc.)

The Tax Reform Act of 1986 lowers the top income tax rate from 50 to 33 percent, while the top estate tax rate is 50 percent for decedents dying in 1988 or later. This difference points to the importance of careful estate planning. Recapitalization can be used to improve the positions of individuals whose estates include stock in closely held corporations. A recapitalization can be used to freeze an estate valuation. The two types of recapitalization are preferred stock and common stock. The IRS considers preferred stock recapitalization to be a form of abuse and is trying to prevent its use. Common stock recapitalizations do not achieve the same estate 'freeze' effect as preferred stock recapitalizations, but the IRS is more likely to allow them.