Many-body aspects of positron annihilation in the electron gas

We investigate positron annihilation in electron liquid as a case study for many-body theory, in particular the optimized Fermi Hypernetted Chain (FHNC-EL) method. We examine several approximation schemes and show that one has to go up to the most sophisticated implementation of the theory available at the moment in order to get annihilation rates that agree reasonably well with experimental data. Even though there is basically just one number to look at, the electron-positron pair distribution function at zero distance, it is exactly this number that dictates how the full pair distribution behaves: In most cases, it falls off monotonously towards unity as the distance increases. Cases where the electron-positron pair distribution exhibits a dip are precursors to the formation of bound electron--positron pairs. The formation of electron-positron pairs is indicated by a divergence of the FHNC-EL equations, from this we can estimate the density regime where positrons must be localized. This occurs in our calculations in the range 9.4 <= r_s <=10, where r_s is the dimensionless density parameter of the electron liquid.Comment: To appear in Phys. Rev. B (2003

Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427/8110) resolved HBV, 8% (628/8110) likely prior HBV vaccination, and 76% (6022/7903) were HBV negative. In those with chronic HBV infection, ≤ 37% received HBV antiviral treatment during the high risk period while 21% to 23% of those with past or resolved HBV, respectively, received HBV antiviral treatment. During and 12 mo after anti-CD20 Ab, the rate of hepatitis was significantly greater in those HBV positive vs negative (P = 0.001). The mortality rate was 35%-40% in chronic or past hepatitis B and 26%-31% in hepatitis B negative. In those pretreatment HBV negative, 16 (0.3%) developed acute hepatitis B of 4947 tested during anti-CD20Ab treatment and follow-up. CONCLUSION: While HBV testing of Veterans has increased prior to anti-CD20 Ab, few HBV+ patients received HBV antivirals, suggesting electronic health record algorithms may enhance health outcomes

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

Opening up the Pandora's box of sustainability league tables of universities: a Kafkaesque perspective

The aim of this paper is to explore the institutional impact of sustainability league tables on current university agendas. It focuses on a narrative critique of one such league table, the UK's ‘Green League Table', compiled and reported by the student campaigning NGO, ‘People & Planet’ annually between 2007 and 2013. Through a Kafkaesque perspective, this paper offers the proposition that such league tables could be acting as an institutional hegemonic mechanism for social legitimacy, through the desire by universities to show that environmental issues are effectively under control. Espoused eco-narratives of the ‘carbon targets imperative’ and ‘engagement' can serve as a form of deception, by merely embracing the narrative as a rhetorical device. Moreover, they can serve the exclusive, particularistic self-interests of a growing legion of ‘carbon managers’, ‘sustainability managers’ and ‘environmental managers' in satisfying the neo-liberal institutional drive from their vice chancellors

Muscarinic receptor-stimulated Ca2+ signaling and inositol lipid metabolism in avian salt gland cells

Activation of muscarinic cholinergic receptors was studied by measuring agonist-stimulated inositol lipid turnover and changes in [Ca2+]i in dissociated salt gland secretory cells. Carbachol stimulation of quin2-loaded cells results in a sustained 4-fold increase in [Ca2+]i, while incorporation of [32P]Pi into phosphatidylinositol (PI) and phosphatidate are similarly increased. [3H]Inositol phosphates, measured in the presence of Li+, increased 13-fold. The stimulated increment in [Ca2+]i required extracellular Ca2+, whereas [3H]inositol phosphate accumulation was independent of external Ca2+. Dose-response curves for carbachol-induced increments in [Ca2+]i, PI labeling, and labeled inositol phosphate release are similar, with EC50 values of 6, 4.5 and 8 [mu]M, respectively. Dissociation constants for atropine vs. the quin2 and phospholipid responses are 0.59 +/- 0.3 nM and 0.48 +/- 0.28 nM, respectively. These cells thus provide a model system for the study of non-exocytotic secretion as a consequence of stimulated inositol lipid turnover.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25973/1/0000039.pd

A cross sectional survey of urban Canadian family physicians' provision of minor office procedures

BACKGROUND: A discordance exists between the proportion of Canadian family physicians that we expect should be able to perform minor office procedures and the actual provision of care. This pattern has not been extensively studied. The objective of this study was to determine the current patterns and obstacles relating to the provision of four minor office procedures by GP/FPs in a small city in Ontario, Canada. An additional goal was to determine the impact of the remuneration method on the provision of such services. METHODS: A survey was mailed to all GP/FPs practising in Kingston, Ontario. The main outcomes measured in the study were work setting and remuneration method, current procedural practices with respect to four procedures, reasons for not performing procedures, current skill levels, and desire to upgrade. RESULTS: Surveys were mailed to all 108 GP/FPs in the City of Kingston. Completed surveys were collected for 82 percent (89/108) and 10 were excluded leaving 79 eligible participants. The percentages of GP/FPs who reported performing the procedure were as follows: dermatological excision (63.3%), endometrial biopsy (35.4%), shoulder injection (31.6%), and knee injection (43.0%). The majority of GP/FPs who would not do the procedure themselves would refer to a specialist colleague rather than to another GP/FP. The top reason cited for not performing a specific procedure was "lack of up to date skills" followed by "lack of time". The latter was the only statistically significant difference reported between GP/FPs working in Family Health Networks and GP/FPs working in fee for service settings (26.7% vs 47.0%, χ(2 )= 4.191 p = 0.041). CONCLUSION: A large number of Kingston, Ontario GP/FPs refer patients who require one of four minor office-based procedures for specialist consultation. Referral to other GP/FP colleagues appears underutilized. A perceived lack of up to date skills and a lack of time appear to be concerns. GP/FPs working in Family Health Networks were more likely to perform these procedures themselves. Further studies would clarify the role of changes in medical education, the role of continuing education, and the impact of different remuneration models