Measurement of the 2νßß Decay Half-Life of

We report on the results obtained with the global CUPID-0 background model, which combines the data collected in the two measurement campaigns for a total exposure of 8.82 kg×yr of ^{82}Se. We identify with improved precision the background sources within the 3 MeV energy region, where neutrinoless double ß decay of ^{82}Se and ^{100}Mo is expected, making more solid the foundations for the background budget of the next-generation CUPID experiment. Relying on the excellent data reconstruction, we measure the two-neutrino double ß-decay half-life of ^{82}Se with unprecedented accuracy: T_{1/2}^{2ν}=[8.69±0.05(stat)_{-0.06}^{+0.09}(syst)]×10^{19} yr.

Erratum: Measurement of the 2νßß Decay Half-Life of

This corrects the article DOI: 10.1103/PhysRevLett.126.171801.

New Direct Limit on Neutrinoless Double Beta Decay Half-Life of

The Cryogenic Underground Observatory for Rare Events (CUORE) at Laboratori Nazionali del Gran Sasso of INFN in Italy is an experiment searching for neutrinoless double beta (0νßß) decay. Its main goal is to investigate this decay in ^{130}Te, but its ton-scale mass and low background make CUORE sensitive to other rare processes as well. In this Letter, we present our first results on the search for 0νßß decay of ^{128}Te, the Te isotope with the second highest natural isotopic abundance. We find no evidence for this decay, and using a Bayesian analysis we set a lower limit on the ^{128}Te 0νßß decay half-life of T_{1/2}>3.6×10^{24} yr (90% CI). This represents the most stringent limit on the half-life of this isotope, improving by over a factor of 30 the previous direct search results, and exceeding those from geochemical experiments for the first time.

Measurement of the 2νßß Decay Half-Life of

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20} yr. This measurement is the most precise determination of the ^{130}Te 2νßß decay half-life to date.

Improved Limit on Neutrinoless Double-Beta Decay in

We report new results from the search for neutrinoless double-beta decay in ^{130} Te with the CUORE detector. This search benefits from a fourfold increase in exposure, lower trigger thresholds, and analysis improvements relative to our previous results. We observe a background of (1.38±0.07)×10^{-2} counts/(keV kg yr)) in the 0νßß decay region of interest and, with a total exposure of 372.5 kg yr, we attain a median exclusion sensitivity of 1.7×10^{25} yr. We find no evidence for 0νßß decay and set a 90% credibility interval Bayesian lower limit of 3.2×10^{25} yr on the ^{130} Te half-life for this process. In the hypothesis that 0νßß decay is mediated by light Majorana neutrinos, this results in an upper limit on the effective Majorana mass of 75-350 meV, depending on the nuclear matrix elements used.

Quality of care indicators for schizophrenia: determinants of observed variations among Italian Departments of Mental Health. Results from the ETAS DSM study.

AIMS: The primary aim of this study is to analyse the conformance of usual care patterns for persons with schizophrenia to treatment guidelines in three Italian Departments of Mental Health (DMHs). The secondary aim is to examine possible organisational and structural reasons accounting for variations among DMHs. METHODS: Within the framework of the Evaluation of Treatment Appropriateness in Schizophrenia (ETAS) project, 20 consensus quality of care indicators were developed. Ten concerned pharmacological treatment and ten encompassed general care and psychosocial rehabilitation interventions. Indicators were calculated using data from a stratified random sample of 458 patients treated at three DMHs located in North-Eastern, North-Western and Southern Italy. Patients' data were collected by combining information from medical charts and from a survey carried out by the health care professionals in charge of the patients. Data on the structural and organisational characteristics of the DMHs were retrieved from administrative databases. For each indicator, the number and percentage of appropriate interventions with and without moderators were calculated. Appropriateness was defined as the percentage of eligible patients receiving an intervention conformant with guidelines. Moderators, i.e., reasons justifying a discrepancy between the interventions actually provided and that recommended by guidelines were recorded. Indicators based on a sufficient number of eligible patients were further explored in a statistical analysis to compare the performance of the DMHs. RESULTS: In the overall sample, the percentage of inappropriate interventions ranged from 11.1 to 59.3% for non-pharmacological interventions and from 5.9 to 66.8% for pharmacological interventions. Comparisons among DMHs revealed significant variability in appropriateness for the indicators 'prevention and monitoring of metabolic effects', 'psychiatric visits', 'psychosocial rehabilitation', 'family involvement' and 'work'. After adjusting the patient's gender, age and functioning, only the indicators 'Prevention and monitoring of metabolic effects', 'psychiatric visits' and 'work' continued to differ significantly among DMHs. The percentage of patients receiving appropriate integrated care (at least one appropriate non-pharmacological intervention and one pharmacological intervention) was significantly different among the three DMHs and lower than expected. CONCLUSIONS: Our results underscore discrepancies among Italian DMHs in indicators that explore key aspects of care of patients with schizophrenia. The use of quality indicators and improved guideline adherence can address suboptimal clinical outcomes, and has the potential to reduce practice variations and narrow the gap between optimal and routine care.

Estudio de los tiempos transcurridos desde el inicio de los síntomas hasta la angioplastia primaria / Analysis of times from symptom on set to percutaneous coronary intervention

Objetivo: El infarto agudo de miocardio con elevación del segmento ST (IAMCEST) requiere un tratamiento precoz y resolutivo. El objetivo de este estudio observacional retrospectivo fue medir la diferencia entre los intervalos temporales desde el inicio de los síntomas y el primer contacto médico (PCM) hasta el inflado de balón. Método: Se recogieron los registros consecutivos de todos los pacientes con IAMCEST que fueron derivados al laboratorio de hemodinámica (LbH) para ser tratados con angioplastia primaria (ACTPp), durante un periodo de 12 meses. Los pacientes se dividieron en dos grupos: grupo A, derivados a LbH desde los sistemas de emergencias médicas (SEM), directamente o a través del servicio de urgencias hospitalario (SUH); y grupo B pacientes que acuden por sus propios medios al SUH. La duración del proceso se calculó en dos intervalos, desde el inicio de síntomas (T1) hasta el inflado de balón y (..) (AU)

Introduction: ST-elevation myocardial infarction (STEMI) must be treated early and aggressively. The aim of this retropective observational study was to measure the times from first medical contact (FMC) to balloon inflation and from symptom onset to balloon inflation. Methods: The consecutive records of all the patients who underwent a primary percutaneous coronary intervention (PCI) for STEMI in the catheterization laboratory over a 12-month period were included. Patients were classified as group A if emergency medical responders brought them directly to the catheterization laboratory or to the emergency department, or group B if they were self-presenters to the emergency department. The duration of the process was calculated in 2 ways, from symptom onset (T1) to balloon inflation and from FMC (T2) to balloon inflation. Relevant medical history and hospital and 30-day (..) (AU)

Menopause and cardiovascular risk.

Menopause is not a disease, but a physiologic phase of a woman's life, due to the changes of their hormonal status. Fastidious symptoms may be associated with changes in the metabolism together with new cardiovascular risk factors, particularly aggressive for the female cardiovascular system, unprepared because of the protection due to the fertile period. Changes of the lipid profile, obesity, hypertension, glucose intolerance and diabetes mellitus may intervene as severe risk factors. Cardiovascular disease represents therefore the most frequent cause of mortality and morbidity also in the female gender more than cancer either in the United States as in Europe. The risks related to post-menopause are mainly due to the abrupt interruption of estrogen, which has indirect protective effects on lipid, glycidic metabolism and direct effects on vessel function. They have, in fact, vasodilator action due to nitric oxide release, calcium-antagonist like action and an antiproliferative effect on smooth muscle cells. Post-menopause is also frequently associated with hypertension, the most frequent related factor to coronary artery disease. Hypertension is due to increased body mass index, with insulin-resistance, sodium retention, increased blood viscosity and estrogen deficiency with increased smooth muscle cell proliferation which determines an increase in systemic vascular resistance. Age and estrogen deficiency are together the most important cause of cardiovascular risk in post-menopause. The discovery of alpha and recently beta estrogen receptors on coronary female vessels unaffected by atherosclerosis either during pre and post-menopause phase are possible key of interpretation of pathophysiology of coronary artery disease in women, with important therapeutic consequence.

Mental health care in Piedmont: a description of its structure and components using a new technology for service assessment.

OBJECTIVE: The northern-Italian region of Piedmont has a total population of 4.3 million. The regional territory is currently divided into 22 local health services, each serving a population not exceeding 300,000 and incorporating a Department of Mental Health. The organization of psychiatric assistance can be described as relatively stable and conforms with the standards imposed by national regulations. Drawing upon previous research experience, and with the support of the relevant regional authorities, our survey implements the methodology developed by the EPCAT team and will eventually embrace about 80% of all local health service areas in this region. METHODS: The survey was preceded by a number of preliminary steps including the training of four researchers, inter-rater reliability testing (particularly for the International Classification of Mental Health Care), and the adjustment of the methodology developed by the EPCAT team to facilitate understanding and use of the instrumentation by the psychiatric professionals involved in the data collection. RESULTS: This paper summarizes data on the structure and components of the mental health service in three areas of Piedmont, with special reference to structures funded by the National Health System. CONCLUSION: Overlooking the imbalances affecting both the resources available for different populations, and the operational profiles of psychiatric agencies of the same type, our data allow an assessment of the descriptive and comparative capabilities of the proposed methodology.

Sarcoidosis presenting with large vessel vasculitis and osteosclerosis-related bone and joint pain.

A 34-year-old African-American female diagnosed earlier with idiopathic thrombocytopenic purpura (ITP), lymphadenopathy, splenomegaly, uveitis, and pulmonary nodules, developed a subclavian artery aneurysm, and generalized annular osteosclerotic lesions with disabling arthralgias. Biopsies from bone and lymph node revealed non-caseating granulomas and no evidence of malignancy or infection, confirming the clinical impression of sarcoidosis.

Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Reprinted from Biotechnology and Bioengineering, Vol. XI, Issue 6, Pages 1101-1110 (1969).

Streptomyces peucetius var. caesius, obtained from S. peucetius, the daunomycin producing microorganism, by mutagenic treatment, differs from the parent culture by the color of the vegetative and aerial mycelia and by its antibiotic producing ability. S. peucetius var. caesius accumulates adriamycin in submerged and aerated culture on a medium containing glucose, brewer's yeast, and inorganic salts both in shake flasks and in stirred fermenters. Isolation of the product is performed by solvent extraction, chromatography on buffered cellulose columns, and crystallization as the hydrochloride. The new antitumor agent, adriamycin, is the 14-hydroxy derivative of daunomycin.

Subclavian artery aneurysm: an unusual manifestation of Takayasu's arteritis.

Complications of Takayasu's arteritis are typically ischemic in nature because of progressive arterial narrowing, with aneurysm formation occurring as a late sequela. A 30-year-old Black woman with Takayasu's arteritis presented with a progressively enlarging and tender pulsatile mass at the base of the right neck. Upper extremity pulses were intact. Chest computed tomography and aortography demonstrated a 6-cm aneurysm of the right subclavian artery, which originated at the takeoff from the innominate artery, which was also ectatic. There was no evidence of occlusive disease. An operation was performed via the median sternotomy with transverse extension into the supraclavicular area. The distal innominate artery, proximal common carotid artery and entire subclavian artery were resected and replaced with a bifurcated stretch ePTFE graft. The aneurysm was without thrombus or atherosclerosis and all vessels were extremely thick-walled. Pathology revealed healed/healing nonspecific arteritis. Aneurysm formation is an unusual complication of Takayasu's arteritis. Previously reported sites of aneurysm formation include the thoracic and abdominal aorta, the innominate, carotid and superior mesenteric arteries, but not the subclavian artery. Of 28 patients enrolled in a recent clinical protocol at the National Institutes of Health with Takayasu's arteritis, none had aneurysm formation. The authors report surgical repair of a large aneurysm of the right subclavian artery in a young Black woman with Takayasu's arteritis.

An aneurysm involving the axillary artery and its branch vessels in a major league baseball pitcher. A case report and review of the literature.

Baseball pitchers appear to be prone to aneurysms of the axillary artery and its branches. The cause is probably related to repetitive compression of or tension on the vessels at the level of the pectoralis minor muscle and the humeral head, which is exacerbated by the pitching motion. The incidence of aneurysms of the axillary artery and its branches among pitchers and other athletes is not known, nor is it clear whether pitchers who are at high risk of vascular injury can be identified before irreversible damage to the vessels has occurred. Perhaps patients who have documented compression or occlusion of the vessel with the arm in the abducted, externally rotated position are at higher risk. Screening pitchers to identify those with axillary artery compression, aneurysm, or thrombosis has also not been shown to be effective. Certainly, many pitchers will have some level of compression of the axillary artery with their arm in the pitching position but will never develop any clinical abnormality requiring treatment. Screening would therefore probably lead to a high false-positive rate. It is clear, however, that pitchers who complain of ischemia-type symptoms such as early fatigue or who have evidence of emboli require a complete evaluation to rule out any abnormality of the axillary artery or one of its branches. Orthopaedic surgeons who see pitchers and other athletes involved in repetitive overhead motions need to be aware of this disorder so that they order the appropriate tests and obtain a vascular consultation--and make a prompt diagnosis. Treatment will vary depending on the type of lesion and on which vessel or vessels are involved, and should be decided on by the team of surgeons treating the patient.

Attenuation of acute lung injury caused by hind-limb ischemia-reperfusion injury by butyrolactone anti-inflammatory agent FL1003.

OBJECTIVE: Activation of systemic inflammation after reperfusion of ischemic tissue results in severe acute lung injury. Neutrophil activation and oxygen radical generation have been implicated in the pathogenesis. This study tested the hypothesis that treatment with FL1003, a butyrolactone with in vitro antioxidant properties, will down-regulate this response and abrogate acute lung injury. METHODS: Male Sprague-Dawley rats (n = 16) were divided into a surgical sham group (n = 4), a group that received 2 hours of ischemia by infrarenal aortic clip followed by 1 hour of reperfusion (n = 7), and an ischemia-reperfusion (I/R) group that received FL1003 100 mg/kg intravenously before ischemia (n = 5). After reperfusion, the heart and lungs were excised en bloc in an isolated lung perfusion apparatus for 1.5 hours of perfusion, while pulmonary artery pressures were held between 5 and 12 mm Hg and venous effluent was collected. Bronchoalveolar lavage fluid and both lungs were harvested at death for determination of tissue water content, pulmonary microvascular permeability, and indicators of neutrophil activation and tissue oxidation. RESULTS: After I/R, there were significant (p < 0.05) increases in intravenous fluid (IVF) requirements (18 +/- 1.2 mL) to maintain hemodynamic stability, wet weight/dry weight ratio of lung tissue, and isolated-lung lavage Ficoll concentrations (0.58 +/- 0.02 microg/mL) compared with sham animals (IVF, 0 mL; Ficoll concentration, 0.08 +/- 0.03 microg/mL). In addition, lung myeloperoxidase activity (0.60 +/- 0.03 vs. 0.12 +/- 0.02 units/g of tissue) and levels of lipid-conjugated dienes (0.042 +/- 0.012 vs. 0.018 +/- 0.006 optical density of 233 nm (OD233)/mL) were significantly higher (p < 0.05) compared with the sham group. In I/R animals treated with FL1003, the IVF requirement (8.5 +/- 1.0 mL), wet weight/dry weight ratio, lung tissue Ficoll concentration (0.21 +/- 0.02 microg/mL), myeloperoxidase concentration (0.217 +/- 0.02 units/g), and lipid-conjugated diene levels (0.012 +/- 0.005 OD233/ mL) were all significantly lower (p < 0.05) than after untreated I/R. CONCLUSION: A pulmonary microvascular permeability defect with pulmonary edema, neutrophil aggregation, and cell membrane damage resulted from ischemia and reperfusion. Treatment of animals with FL1003 significantly attenuated the inflammatory response associated with acute lung injury.

Ischemia-reperfusion injury in myocutaneous flaps: role of leukocytes and leukotrienes.

Leukotriene B4 is a potent inflammatory mediator that is derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and that has been implicated in the pathophysiology of polymorphonuclear leukocyte-dependent reperfusion injury in a variety of organ systems. The objectives of these investigations were to determine whether inhibition of leukotriene B4 attenuates postischemic polymorphonuclear leukocyte infiltration and subsequent injury in myocutaneous flaps. Anesthetized female Yorkshire pigs were randomized to receive normal saline (n = 8), the 5-lipoxygenase inhibitor diethylcarbamazine (n = 7), or the leukotriene B4 receptor antagonist SC-41930 (n = 7). All animals underwent 6 hours of rectus abdominis myocutaneous flap ischemia followed by 4 hours of reperfusion. In saline-treated controls, flap ischemia was associated with massive polymorphonuclear leukocyte infiltration at 1 and 4 hours of reperfusion (252 +/- 70 and 619 +/- 137 polymorphonuclear leukocytes per 25 high-power fields, respectively). Skeletal muscle neutrophil content was significantly attenuated by pretreatment with diethylcarbamazine (72 +/- 29 and 229 +/- 63 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05) or SC-41930 (25 +/- 3 and 193 +/- 25 polymorphonuclear leukocytes per 25 high-power fields; p < 0.05). Wet-to-dry weight ratios of full-thickness flap biopsies were lower in the diethylcarbamazine and SC-41930 groups (2.98 +/- 0.15 and 2.90 +/- 0.26, respectively) than in the control group (4.13 +/- 0.23; p < 0.01), and mean muscle infarct size, as determined by nitroblue tetrazolium staining, diminished from 47.6 +/- 11.3 percent in controls to 25.1 +/- 6.5 percent in diethylcarbamazine-treated animals and 7.3 +/- 4.8 percent in SC41930-treated animals (p < 0.05). These data indicate that leukotriene B4 plays a critical role in mediating neutrophil-dependent injury in postischemic skeletal muscle flaps.

Acquired protein S and antithrombin III deficiency caused by nephrotic syndrome: an unusual cause of graft thrombosis.

Thrombotic phenomena are well-recognized complications of nephrotic syndrome attributable to loss of intermediate-sized antithrombotic proteins in the urine, resulting in a hypercoaguable state. As such, nephrotic syndrome may be associated with a reduction in circulating antithrombin III and free protein S levels. Associated spontaneous thrombotic complications are generally venous in nature, with arterial thrombosis occurring less frequently. Hypercoagulability caused by acquired nephrotic syndrome has not generally been recognized as a cause of acute thrombosis of arterial bypass grafts. We report two patients who after having nephrotic syndrome sustained acute thrombosis of their arterial bypass grafts. Pathogenesis and management are discussed.

Lactate blood levels in the perioperative period of orthotopic liver transplantation.

To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P < or = 0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/l in 47 of 49 patients from group A, while they plateaued above 4 mmol/l in all patients from group B. Group A patients had lower alanine aminotransferase levels (P < or = 0.001), higher prothrombin activity, (P < or = 0.01), and greater bile flow (P < or = 0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.

Mechanisms of cerebrovascular dysfunction.

Cerebrovascular dysfunction characterized by the loss of endothelial integrity has been observed following ischemic and traumatic insults to the brain, resulting in the net movement of fluid and solute out of the intravascular space and into the interstitium. Following traumatic brain injury, the development of intracranial hypertension secondary to cerebral edema plays a major role in the high morbidity and mortality in these patients. Although the precise mechanisms responsible for the disruption of the normally tightly regulated cerebrovascular tissue interface remain unclear, there is increasing evidence implicating inflammatory events in this process through the transient opening of tight junctional complexes. This article will examine the interaction of astrocytes, activated neutrophils, and inflammatory mediators in inducing endothelial contraction, thereby physically opening the permeability barrier and allowing the net movement of fluid out of the intravascular space.

Reperfusion injury of postischemic skeletal muscle is attenuated by the 21-aminosteroids U-74389F and U-74500A independent of iron binding.

BACKGROUND: Lazaroids (21-aminosteroids) are a novel class of compounds that have been shown to limit experimental ischemic injury of varied causes. The mechanism of action is uncertain but may include scavenging of lipid peroxy radicals, iron binding, or direct membrane interaction. The purpose of these experiments was to evaluate the capacity of the lazaroids U-74500A and U-74389F to modify ischemia/reperfusion injury of skeletal muscle in a well-characterized model of high-grade partial ischemia. METHODS: Nonfasted male Sprague-Dawley rats were anesthetized, a tracheostomy tube was placed, and the carotid artery and jugular vein were cannulated. Animals received heparin (1 unit/gm) and crystalloid (1 ml/hr) intravenously. The baseline group (n = 6) was allowed a 30-minute equilibration period, after which resting transmembrane potential (Em) was measured in a hindlimb muscle. Muscle biopsy specimen was obtained; conjugated diene and thiobarbituric acid reactive substances were measured as indexes of lipid peroxidation. Spectrophotometric determination of plasma iron and unsaturated iron-binding capacity were performed (total iron-binding capacity and percent saturation were calculated). Animals received U-74389F (2 mg/kg, n = 7), U-74500A (2 mg/kg, n = 6), or vehicle only (0.02 mol/L citrate acid/citrate; n = 7) intraarterially before infrarenal aortic clamping was performed for 120 minutes. An additional group of animals received U-74389F (2 mg/kg, n = 7), U-74500A (2 mg/kg, n = 7), or vehicle (n = 11) intraarterially before infrarenal aortic clamping was performed for 120 minutes, followed by reperfusion for 30 minutes. RESULTS: Depolarization of resting Em was noted during ischemia, with partial repolarization on reperfusion, which was enhanced by either lazaroid. As expected, iron delocalization occurred during ischemia and persisted on reperfusion, with U-74500A effectively binding iron, whereas U-74389 did not. Vehicle but not the 21-aminosteroids inhibited lipid peroxidation. CONCLUSIONS: High-grade partial ischemia of skeletal muscle is associated with iron delocalization, which persists on reperfusion. Each lazaroid achieved a similar "membranoprotective" effect during reperfusion only despite lack of iron binding by U-74389F, suggesting a direct interaction with the cell membrane. These data support the concept that ischemic injury and reperfusion injury occur through fundamentally different mechanisms.