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

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

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.

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.

Neutrophil leukotriene generation and pulmonary dysfunction after abdominal aortic aneurysm repair.

BACKGROUND: The purpose of this study was to assess the role of polymorphonuclear neutrophil (PMN)-generated leukotriene B4 (LTB4) as an etiologic agent in the pulmonary dysfunction seen after operation in patients undergoing abdominal aortic aneurysm repair. METHODS: Blood was analyzed in 10 consecutive patients undergoing elective infrarenal abdominal aortic aneurysm repair for plasma thromboxane B2, lactoferrin, C3a, and PMN-generated LTB4. RESULTS: There was a close linear correlation (r = 0.88; p < 0.001) between aortic clamp time and PMN LTB4 production. Conversely, aortic clamp time and the ratio of arterial oxygen pressure to fraction of inspired oxygen, a measure of pulmonary function, were inversely related (r = -0.80; p < 0.008). PMNs from patients with long aortic cross-clamp times generated three times more LTB4 than those patients with short cross-clamp times (194 +/- 29.6 vs 64.9 +/- 9.7 ng per 5 x 10(6) PMN; p < 0.05). Similarly, the pressure/inspired oxygen ratio was significantly lower on admission to the intensive care unit in patients with long cross-clamp times as compared with patients with short cross-clamp times (237 +/- 14 vs 342 +/- 5; p < 0.005). In addition, patients with long cross-clamp times remained intubated longer than patients with short times (1.6 +/- 0.2 vs 0.6 +/- 0.4 days; p < 0.05). CONCLUSIONS: These data suggest a causal role for LTB4 in the generation of pulmonary dysfunction in patients undergoing abdominal aortic aneurysm repair, similar to what has been shown in animal models.

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.

Effect of hypothermia on cellular membrane function during low-flow extracorporeal circulation.

The use of systemic hypothermia is known to allow recovery from potentially lethal states of profound hypoperfusion or total circulatory arrest. While the cellular alterations accompanying states of decreased perfusion in skeletal muscle are well defined, little is known regarding the impact of coexistent hypothermia. To investigate this issue, nine dogs were placed on total cardiopulmonary bypass (CPB) and perfused in nonpulsatile fashion. The following flow and temperature parameters were used in three different perfusion models: 3.5 L/min/m2 at 23 degrees C (group A, n = 3), 1.6 L/min/m2 at 37 degrees C (group B, n = 3), and 1.6 L/min/m2 at 23 degrees C (group C, n = 3). Assessment of cellular function in a hind limb adductor muscle by measurement of resting transmembrane potential difference (Em) and determination of tissue electrolyte distribution in a biopsy specimen was performed in the control state and again after 60 minutes of total CPB. Low-flow/hypothermic CPB (group C) was associated with depolarization of resting Em to -63.3 +/- 3.2 mV from a control value of -87.0 +/- 1.3 mV (p less than 0.05), an increase in the calculated intracellular Na ([Na]i) to 16.4 +/- 4.0 mEq/L from a control value of 7.6 +/- 1.4 mEq/L (p less than 0.05), and an increase in the ratio of the selective membrane permeabilities of Na+ to K+ (pNa/pK), to 0.067 +/- 0.013 from a control value of 0.013 +/- 0.002 (p less than 0.05). In contrast, resting Em was maintained at -86.4 +/- 6.1 mv during normal-flow/hypothermic CPB (group A), while low-flow/normothermic CPB (group B) produced an intermediate depolarization to -75.2 +/- 3.0 mV (p less than 0.05). Neither [Na]i or pNa/pK was altered significantly in group A or group B dogs. These data characterize a physiologic alteration in the cellular membrane function of skeletal muscle during low-flow/hypothermic CPB, which is similar in many respects to that accompanying hemorrhagic shock. This suggests that during periods of profound hypothermia certain flow-related derangements in skeletal muscle are not obviated and may be exacerbated.

Effect of hormonal and substrate backgrounds on cell membrane function in normal males.

Hormonal and substrate influences on in vivo cellular membrane function were evaluated in 15 healthy male volunteers. Each subject underwent serial evaluations of membrane function in the anterior tibialis muscle, as assessed by transcutaneous measurement of resting membrane potential (Em). Group A subjects (n = 9) underwent measurement of resting Em in the basal state and again during the 10th day of intravenous feeding (IVF). Group B subjects (n = 6) underwent measurement of resting Em in the basal state during epinephrine infusion and again during epinephrine infusion on the 7th day of IVF. Percutaneous needle biopsy of the vastus lateralis muscle permitted calculation of transmembrane electrolyte distribution from the Nernst equation, using the measured Em and the chloride space method. Hospitalization with intake of a defined-formula enteral diet for 3 days resulted in depolarization (P less than 0.05) of resting Em (-75.3 +/- 1.6 mV) compared with normal (-79.8 +/- 0.9 mV). Despite 10 days of subsequent IVF, further depolarization (P less than 0.05) of resting Em (-71.2 +/- 1.2 mV) was observed. In the dual presence of IVF and exogenous epinephrine infusion, there was an increase (P less than 0.05) in intracellular potassium concentration and repolarization of resting Em (-80.6 +/- 0.8 mV) to normal levels. These data indicate that hormonal background and substrate availability contribute to the in vivo modulation of cellular membrane function in human skeletal muscle, possibly through facilitation of sodium-dependent amino acid transport across the cell membrane.

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.

Reserving supraclavicular first rib resection for vascular complications of thoracic outlet syndrome.

BACKGROUND: The traditional approach to decompression of the thoracic outlet has been by transaxillary resection of the first rib. Recently, the trend has been toward a more selective and tailored surgical approach via the supraclavicular route. METHODS: During a 51-month period, 14 consecutive patients underwent decompressive surgery of the thoracic outlet via the supraclavicular approach. There were ten women and four men; mean age was 44 years. Indications for operation were arterial (n = 3), venous (n = 2) and neurogenic (n = 9). Mean follow-up was 31 months. Operation consisted of resection of the anterior scalene and medial aspect of the middle scalene muscles and brachial plexus neurolysis for neurogenic indication, with first rib resection reserved for vascular complications. RESULTS: Operations performed for vascular complication were successful and uncomplicated, with good clinical outcome. Seven of nine operations (78%) performed for neurogenic indication produced marked relief of symptoms, while two (22%) resulted in no clinical change. Complications consisted of transient scapular winging (n = 1) and transient diaphragmatic paralysis (n = 2). CONCLUSIONS: A selective approach to thoracic outlet decompression, consisting of anterior scalenectomy and brachial plexus neurolysis for neurogenic symptoms, and reserving first rib resection for arterial and venous indications, is a safe procedure and yields satisfactory results in appropriately selected patients.

Qualitative and quantitative fluorescein fluorescence in determining intestinal viability.

Clinical evaluation and qualitative (visual) and quantitative (fluorometric) fluorescence for predicting intestinal viability were compared in an animal model of temporary arterial occlusion with early revascularization. Quantitative fluorescence was determined with a perfusion fluorometer after an intravenous bolus of fluorescein. Qualitative fluorescence was determined by examination under a Wood's lamp in a darkened room. The effectiveness of each diagnostic technique in determining nonviability was expressed in terms of sensitivity, specificity, and accuracy. All three methods had 100 percent specificity; only bowel deemed nonviable proved to be so. Quantitative fluorescence also had a 100 percent sensitivity, but clinical evaluation and qualitative fluorescence had only a 33 and 11 percent sensitivity, respectively (some segments of bowel that were ultimately nonviable were not correctly predicted to be so). The inaccuracy of qualitative fluorescence was due to the fact that ischemic intestine with a hyperfluorescent pattern often progressed to necrosis. Fluorometric quantitation identified those hyperfluorescent segments that were viable. This study suggests that visual fluorescence is not reliable in assessing intestinal viability after early revascularization after arterial occlusion, but quantitative fluorometric fluorescence is reliable in almost all instances.

Pulmonary failure following lower torso ischemia: clinical evidence for a remote effect of reperfusion injury.

Acute lung injury as a remote sequela of severe lower torso ischemia-reperfusion has been demonstrated experimentally, in a process involving leukosequestration and generation of the arachidonate derivatives thromboxane and leukotriene B4. However, contemporary clinical reports have been limited to development of transient, subclinical "reperfusion pulmonary edema" several hours after declamping in patients undergoing elective abdominal aortic aneurysm repair. This report refocuses attention on the clinical syndrome of severe, acute deterioration in pulmonary function occurring several hours after restoration of perfusion to an ischemic lower torso in two patients. The lung injury is characterized by progressive hypoxemia, pulmonary hypertension, decreased lung compliance, and non-hydrostatic pulmonary edema, consistent with adult respiratory distress syndrome (ARDS). This report reinforces the concept that humoral mediators generated at reflow may induce end-organ injury at a site remote from the focus of ischemia-reperfusion, and that the lung is a target organ.

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.

Echocardiographic monitoring of mental stress test in ischemic heart disease.

Mental stress testing can induce ischemia in coronary patients, but often may not induce chest pain and/or electrocardiographic changes. Therefore, we tested the utility of echocardiography to increase the sensitivity of the method. For this purpose, 56 patients undertook arithmetic mental stress tests and then were subjected to coronary angiography. During the test we evaluated left ventricular function, electrocardiography results, and emotional involvement measured by STAI (State Trait Anxiety Inventory). Echocardiography was positive in 21 patients, and electrocardiogram only in 2 patients. No patient complained of chest pain. The remaining 35 patients were negative. Comparing echo data with coronary angiography, in all the cases, sensitivity was 73.5%, specificity 93.3%. Analysis of the STAI revealed that the negative test we observed could be due to a low stressor efficacy. In conclusion, echocardiography in mental stress testing permits improved sensitivity, with loss of specificity in comparison with conventional electrocardiographic monitoring.

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.

Iron and cardiovascular dysfunction: mechanisms and therapeutic implications.

It has been recognized for over three decades that tissue hypoperfusion is associated with the appearance of increased levels of iron in the plasma. Experimental observations have documented the liberation of iron into the circulation following reperfusion of ischemic myocardium and small intestine, and into the urine following renal ischemia-reperfusion. Similarly, we have recently demonstrated that iron is delocalized during ischemia of skeletal muscle, via a process which persists upon reperfusion. Other studies have demonstrated delocalization of iron in the parenchyma of postischemic brain, myocardium, and kidney.

Nitric oxide and cardiovascular dysfunction.

Prior to the mid-1980s, nitric oxide (NO) was viewed as an environmental pollutant but not as a compound of physiological significance. Thus, it was a skeptical audience that first heard the pronouncement at a scientific meeting in 1986, that NO was the identity of the elusive endothelium-derived relaxing factor, a mediator of vasorelaxation in response to numerous endogenous stimuli. Since then, the simple gas NO has gone from obscurity to center stage, being identified as a key player in physiologic processes as diverse as blood pressure maintenance, neural transmission, and immunologic defense. In addition to its physiological roles, NO has been implicated in the pathogenesis of a multitude of disease states, many of which are of primary interest to the cardiovascular surgeon: circulatory shock, atherosclerosis, diabetes mellitus, and ischemia-reperfusion injury. Recent years has seen NO biology emerge as an exciting and extremely fertile area of biomedical investigation. To fully understand the molecular basis of many clinical problems facing the cardiovascular surgeon, appreciation of NO's involvement is essential.

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.