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 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.

Diagnosis and management of endometriosis: a systematic review of international and national guidelines.

BACKGROUND: The development of clinical guidelines requires standardised methods informed by robust evidence synthesis. OBJECTIVES: We evaluated the methodological quality of endometriosis guidelines, mapped their recommendations, and explored the relationships between recommendations and research evidence. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and PubMed from inception to February 2016. SELECTION CRITERIA: We included guidelines related to the diagnosis and management of endometriosis. DATA COLLECTION AND ANALYSIS: The search strategy identified 879 titles and abstracts. We include two international and five national guidelines. Four independent authors assessed the methodological quality of the included guidelines, using the Appraisal of Guidelines for Research & Evaluation (AGREE-II) instrument, and systematically extracted the guideline recommendations and supporting research evidence. MAIN RESULTS: One hundred and fifty-two different recommendations were made. Ten recommendations (7%) were comparable across guidelines. The European Society of Human Reproduction and Embryology was objectively evaluated as the highest quality guideline (methodological quality score: 88/100). There was substantial variation between the supporting evidence presented by individual guidelines for comparable recommendations. Forty-two recommendations (28%) were not supported by research evidence. No guideline followed the standardised guideline development methods (AGREE-II). CONCLUSIONS: There is substantial variation in the recommendations and methodological quality of endometriosis guidelines. Future guidelines should be developed with reference to high-quality methods in consultation with key stakeholders, including women with endometriosis, ensuring that their scope can truly inform clinical practice and eliminate unwarranted and unjustified variations in clinical practice. TWEETABLE ABSTRACT: #Endometriosis guidelines vary in recommendations and quality. @EndometriosisUK.

Diagnostic accuracy of cancer antigen 125 for endometriosis: a systematic review and meta-analysis.

BACKGROUND: The development of a non-invasive and accurate diagnostic biomarker for endometriosis is urgently needed. OBJECTIVE: Evaluate the diagnostic accuracy of serum cancer antigen 125 (CA 125) for endometriosis. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and Web of Science from inception to January 2016. SELECTION CRITERIA: Diagnostic accuracy studies of serum CA 125 (index test) for histologically confirmed endometriosis (reference standard) were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted study characteristics and data. Methodological quality was assessed using Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist. MAIN RESULTS: Twenty-two studies (16 cohort, six case-control), 3626 participants, were identified. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89-95%) and sensitivity 52% (95% CI 38-66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47-77% versus 24%, 95%CI 19-32%, P-value = 0.001). CONCLUSIONS: CA 125 performs well as a rule-in test facilitating expedited diagnosis and ensuring investigation and treatment can be confidently tailored for the management of endometriosis. Unfortunately, a negative test, CA 125 < 30 units/ml, is unable to rule out endometriosis. TWEETABLE ABSTRACT: Blood test CA 125: a rule-in test for the diagnosis of women presenting with symptoms of endometriosis.

Burnout and self-reported quality of care in community mental health.

Staff burnout is widely believed to be problematic in mental healthcare, but few studies have linked burnout directly with quality of care. The purpose of this study was to examine the relationship between burnout and a newly developed scale for quality of care in a sample of community mental health workers (N=113). The Self-Reported Quality of Care scale had three distinct factors (Client-Centered Care, General Work Conscientiousness, and Low Errors), with good internal consistency. Burnout, particularly personal accomplishment, and to a lesser extent depersonalization, were predictive of overall self-rated Quality of Care, over and above background variables.

Lightning-induced intensification of the ionospheric sporadic E layer.

A connection between thunderstorms and the ionosphere has been hypothesized since the mid-1920s. Several mechanisms have been proposed to explain this connection, and evidence from modelling as well as various types of measurements demonstrate that lightning can interact with the lower ionosphere. It has been proposed, on the basis of a few observed events, that the ionospheric 'sporadic E' layer--transient, localized patches of relatively high electron density in the mid-ionosphere E layer, which significantly affect radio-wave propagation--can be modulated by thunderstorms, but a more formal statistical analysis is still needed. Here we identify a statistically significant intensification and descent in altitude of the mid-latitude sporadic E layer directly above thunderstorms. Because no ionospheric response to low-pressure systems without lightning is detected, we conclude that this localized intensification of the sporadic E layer can be attributed to lightning. We suggest that the co-location of lightning and ionospheric enhancement can be explained by either vertically propagating gravity waves that transfer energy from the site of lightning into the ionosphere, or vertical electrical discharge, or by a combination of these two mechanisms.

AT4 receptor activation increases intracellular calcium influx and induces a non-N-methyl-D-aspartate dependent form of long-term potentiation.

The angiotensin 4 receptor (AT4) subtype is heavily distributed in the dentate gyrus and CA1-CA3 subfields of the hippocampus. Neuronal pathways connecting these subfields are believed to be activated during learning and memory processing. ur laboratory previously demonstrated that application of the AT4 agonist, Norleucine1-angiotensin IV, enhanced baseline synaptic transmission and long-term potentiation, whereas perfusion with the AT4 antagonist, Norleucine1-Leu3-psi(CH2-NH2)3-4-angiotensin IV disrupted long-term potentiation stabilization in area CA1. The objective of the present study was to identify the mechanism(s) responsible for Norleucine1-angiotensin IV-induced increase in hippocampal long-term potentiation. Hippocampal slices perfused with Norleucine1-angiotensin IV for 20 min revealed a notable increase in baseline responses in a non-reversible manner and were blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione disodium salt. Infusions of Norleucine1-angiotensin IV prior to, but not after theta burst stimulation, significantly enhanced long-term potentiation compared with control slices. Further, N-methyl-D-aspartate receptor-independent long-term potentiation could be induced by tetanization during the perfusion of Norleucine1-angiotensin IV in the presence of the N-methyl-D-aspartate antagonist, D,L-2-amino-5-phosphonovaleric acid. Blockade of select voltage dependent calcium channels significantly reduced Norleucine1-angiotensin IV-induced increase in baseline responses and subsequent long-term potentiation suggesting that AT4 receptor activation increases intracellular calcium levels via altering voltage dependent calcium channels and triggers an N-methyl-D-aspartate-independent form of long-term potentiation. In support of this notion the application of Nle1-angiotensin IV to cultured rat hippocampal neurons resulted in increased intracellular calcium derived exclusively from extracellular sources. Consistent with these observations Nle1-angiotensin IV was capable of augmenting the uptake of 45Ca2+ into rat hippocampal slices. Taken together, these data indicate that increased calcium influx through postsynaptic calcium channels contribute to Norleucine1-angiotensin IV-induced enhancement of long-term potentiation.

Classification of canine urinary bladder urothelial tumours based on the World Health Organization/International Society of Urological Pathology consensus classification.

One hundred canine urinary bladder urothelial (transitional cell) tumours, including roughly equal numbers of benign and malignant forms, were retrospectively categorized in accordance with the newly described human consensus classification of the World Health Organization/International Society of Urological Pathology (WHO/ISUP). The tumours were reviewed and classified by three veterinary pathologists from Michigan State University and two human pathologists from the Armed Forces Institute of Pathology (AFIP). The current human WHO/ISUP classification system was considered to be readily applicable to the dog. Canine tumours, however, differed from human tumours in that the great majority showed extensive glandular differentiation (or metaplasia) and hyperplastic lesions tended to be more florid than those seen in human beings. The various diagnoses and grades assigned to the tumours were highly consistent between all reviewing pathologists. This paper presents the salient features of the new WHO and ISUP consensus classification and provides illustrations of the various tumour types that were directly applicable to the dog.

The neuropathy of abetalipoproteinemia.

The clinical, electrophysiologic, and pathologic features of the peripheral neuropathy in abetalipoproteinemia (Bassen-Kornzweig disease) have been described incompletely. On the basis of findings in threee patients, we believe that large muscle fibers in peripheral nerves are selectively affected and that weakness may be due to chronic partial denervation.

Renal medullary carcinoma. The seventh sickle cell nephropathy.

Over the last 22 years, we have encountered 34 examples of a highly aggressive neoplasm with a microscopic morphology that is highly predictive of finding sickled erythrocytes in the tissue. With the exception of one patient, all are believed to have had sickle cell trait or, in one case, hemoglobin SC disease. These 33 patients are the subject of this report and, where their race was known, they were all blacks between the ages of 11 and 39 years. Between the ages of 11 and 24 years, males predominated by 3 to 1. Beyond age 24, however, the tumors occurred equally in men and women. The dominant tumor mass was in the medulla and ranged from 4 to 12 cm in diameter. Mean size was 7 cm; median, 6 cm. Peripheral satellites in the renal cortex and pelvic soft tissues, as well as venous and lymphatic invasion, were usually present. The lesions exhibited a reticular, yolk sac-like, or adenoid cystic appearance, often with poorly differentiated areas in a highly desmoplastic stroma admixed with neutrophils and usually marginated by lymphocytes. The tumors had usually metastasized when first discovered, and none was confined to the kidney at the time of nephrectomy. The mean duration of life after surgery was 15 weeks. These tumors probably arise in the calyceal epithelium in or near the renal papillae, the same site that produces the more familiar picture of unilateral hematuria in patients with sickle cell trait. We have concluded that renal medullary carcinoma represents another example of renal disease associated with sickle cell disorders. The other six are unilateral hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate urine, and pyelonephritis.

Metanephric adenoma. Clinicopathological study of fifty patients.

We report 50 examples of an uncommon type of renal adenoma from the files of the Armed Forces Institute of Pathology. They appear to be benign tumors with no malignant potential, and their chief importance is related to the fact that they are most often misinterpreted as renal cell carcinoma or epithelial Wilms' tumor. They predominated in females by well over 2:1. The mean age of the patients was 41 years, with a range of 5 to 83 years, and the mean size was 5.5 cm, with a range of 0.3 to 15.0 cm. Presenting signs and symptoms included pain in 11, hematuria in five, and palpable mass in five. In 20 patients the tumors were found incidentally during evaluation for other problems, and in six the other problem was polycythemia. This finding establishes a higher incidence of polycythemia in renal adenoma than in other previously reported renal diseases. Also of preoperative importance is the fact that these tumors are more commonly calcified than other renal neoplasms. Microscopically, these tumors consist of very small epithelial cells that form very small acini in an acellular stroma. Less often, they form tubular, glomeruloid, or polypoid and papillary formations. Most also show evidence of regression in the form of scarring and calcification. These lesions seem histogenetically related to epithelial Wilms' tumor, and, in fact, the two may occur together. They are histologically very similar to the metanephric hamartomatous element of nephroblastomatosis.

A distinctive myointimal proliferation ('myointimoma') involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases.

This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.

Smooth muscle hyperplasia of the testicular adnexa clinically mimicking neoplasia: clinicopathologic study of sixteen cases.

Sixteen cases of a largely unrecognized benign cause for an intrascrotal mass are reported herein. These cases represent a nonneoplastic excess of native smooth muscle in the paratestis or spermatic cord growing between or around vessels or efferent ducts. The patients ranged in age from 46 to 81 years, with a mean age of 63 years. The size, available in 10 of the cases, ranged from 6 mm to 7 cm, with a mean of 2.5 cm; there was no side predilection. Microscopically, the lesions consisted of fascicles of smooth muscle, growing in a periductal, perivascular, interstitial, or mixed pattern. The cohesive, interlacing growth pattern of a leiomyoma was missing in all cases. The cause of this lesion is not apparent, although microscopic epididymal or vas deferens duct ectasia in some cases suggests a possible obstructive etiology. In any case, these are benign and without clinical significance after excision and correct diagnosis. Follow-up was available in 13 patients with no recurrences observed from 1 month to 16 years postoperatively.

Differential patterns of local cerebral glucose utilization in response to 5-hydroxytryptamine agonists.

Local cerebral glucose utilization was measured in parallel groups of conscious rats following intravenous injection of either 1 mg/kg 8-hydroxy-2-(di-N-propylamino)tetralin (a 5-hydroxytryptamine 1A binding site agonist), 3 mg/kg 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole, succinate (a 5-hydroxytryptamine1B agonist), or saline alone, using the 2-deoxyglucose quantitative autoradiographic techniques (n = 5 in each of the three groups). Following both drugs, local rates of glucose use in the majority of the 72 brain areas analysed remained unaltered, but in some other regions either increases or decreases were observed. In keeping with the observed behavioural response to 8-hydroxy-2-(di-N-propylamino)tetralin there were marked increases in cerebellum (+56%) and motor cortex where a columnar arrangement of increased metabolism (+34%) contrasted with adjacent columns of decrease (-26%). Hippocampal areas showed moderate decreases in glucose use (-13 to -21%). All areas which increased following 8-hydroxy-2-(di-N-propylamino)tetralin also increased following 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole, succinate, but in the latter case all elements of the basal ganglia were also increased, including globus pallidus (+105%) and the striatum where the changes (+54%) were limited to a discrete dorsal region of the nucleus. In the hippocampus only dorsal dentate gyrus was decreased (-24%) whilst a moderate increase (+16%) was observed in dorsal subiculum. The complexity of these results contrasts with previous 2-deoxyglucose investigations where less specific 5-hydroxytryptamine receptor ligands were used, and suggests that certain aspects of brain function may be selectively targeted by systemic pharmacological manipulation of endogenous serotonergic systems.

Evidence for presynaptic 5-hydroxytryptamine3 recognition sites on vagal afferent terminals in the brainstem of the ferret.

Antagonists acting at the 5-hydroxytryptamine3 receptor are potent anti-emetic agents in cases of cytotoxic- and radiation-induced vomiting, and binding sites for these compounds have been described in brainstem areas known to be involved in mediation of nausea and vomiting. We have used autoradiography to examine the distribution of one of these antagonists, [3H]granisetron in the caudal brainstem of the ferret, a commonly used animal model for physiological investigations of emesis. The highest density of binding sites was found to be in the dorsomedial region of the nucleus of the solitary tract, the principal terminus for gastric vagal afferent fibres. Lower levels of binding were observed in the area postrema and the dorsal motor nucleus of the vagus. Following unilateral nodose ganglion excision, displaceable binding of [3H]granisetron in the nucleus of the solitary tract was attenuated on the ipsilateral side by 65%. Bilateral subdiaphragmatic vagotomy abolished binding of [3H]granisetron in the entire dorsal vagal complex. These results provide strong circumstantial evidence that 5-hydroxytryptamine3 receptors are located on vagal afferent terminals in the ferret brainstem.

Prostatic carcinoma: problems in the interpretation of prostatic biopsies.

We have endeavored to identify problems the pathologist may face in dealing with prostatic carcinoma (PCa). We have covered criteria for diagnosis and have discussed lesions that simulate PCa and the distinguishing features, treatment effects, and specific types of PCa. In many of these areas there is a need for developing objective, reproducible, and measurable criteria. The need for research is obvious.

Simple and rapid visual sensing of saccharides.

Solutions of compound 1 exhibit dramatic, characteristic color changes in response to sugar analytes. Structurally related saccharides including glucose phosphates and amino and carboxylic acid sugars can be readily distinguished by visual inspection. These findings should promote the design of unique color sensory materials based on readily available, functional macrocyclic hosts.

Solid-state supramolecular structures of resorcinol-arylboronic acid compounds.

[structure: see text] An X-ray crystallographic study of unique hydrogen-bonded supramolecular solid-state networks comprised of a tetraarylboronic acid resorcinarene is described. When 1 is recrystallized from 9:1 MeOH:EtOH, partial esterification takes place to give compound 2, the corresponding half methyl ester, which forms an infinite two-dimensional array. Each molecule participates in 12 hydrogen bonds with other macrocycles. These hydrogen bonds are both B-OH- - - OH (phenolic) and OH (phenolic)- - -OH (phenolic).