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The principal aim of this article is to attach and study $p$-adic $L$-functions to cohomological cuspidal automorphic representations $\Pi$ of $\operatorname {GL}_{2n}$ over a totally real field $F$ admitting a Shalika model. We use a modular symbol approach, along the global lines of the work of Ash and Ginzburg, but our results are more definitive because we draw heavily upon the methods used in the recent and separate works of all three authors. By construction, our $p$-adic $L$-functions are distributions on the Galois group of the maximal abelian extension of $F$ unramified outside $p\infty$. Moreover, we work under a weaker Panchishkine-type condition on $\Pi _p$ rather than the full ordinariness condition. Finally, we prove the so-called Manin relations between the $p$-adic $L$-functions at all critical points. This has the striking consequence that, given a unitary $\Pi$ whose standard $L$-function admits at least two critical points, and given a prime $p$ such that $\Pi _p$ is ordinary, the central critical value $L(\frac {1}{2}, \Pi \otimes \chi )$ is non-zero for all except finitely many Dirichlet characters $\chi$ of $p$-power conductor.

For optimal diabetes management HbA1c, lipid and renal function measurements are key. Suitable point-of-care systems can provide such data in remote areas, diabetes camps, disaster relief, small community hospitals and in community screening days in disadvantaged regions. Some systems are currently used in Australian rural, remote and indigenous health services.

AIM: To measure skin autofluorescence in youth (

Background There is a global concern that physician-researchers are 'a dying breed'. Recent studies of clinical career choices of Australian medical students and doctors have signalled the rising age of medical graduates, generational shifts in work-life attitudes and increased proportion of female graduates. There are scant data regarding Australian physician-researchers. Aims To develop and utilise a questionnaire determining respondent characteristics and 'push' and 'pull' factors for medical graduates to incorporate research into their careers. Methods We developed and administered an 88-item online survey, including quantitative and qualitative questions, to medical students, faculty and alumni of Sydney Medical School, The University of Sydney, asking about their medical career, research experience and interest and reasons for doing or not doing medical research. Responses to all 74 quantitative questions are reported here. Results Data from 427 respondents (44% female; mean ± standard deviation age 38 ± 13 years; 56% completed or undertaking a PhD) were analysed. Attractions of research included a desire to improve human health, intellectual stimulation and career diversity. Barriers included low funding rates, job insecurity and low salaries. Although few were prepared to undertake or recommend full-time research, 71% would recommend part-time research. Respondents perceived a smaller-than-actual gap between clinical and research salaries, and if comparable (75-100% of a clinician's) salaries were available, 89% would like to spend 21-60% of their work time undertaking research. Conclusion Many Australian medical students and doctors are interested in research, especially part time. Perceived obstacles include job insecurity, low funding rates and salary. Respondents underestimated clinical and research salary differences.

BACKGROUND: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education. AIM: To develop and utilise a survey to evaluate patient self-management of overnight glycaemia in adults with T1D. METHODS: Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self-management and glycaemic control, including responses to hypothetical pre-bed blood glucose (BG) levels (4-20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA with significance considered at P < 0.05. RESULTS: There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006. CONCLUSIONS: Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self-management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.

Summary High perceptual load reduces distractor processing and increases inattentional blindness for unexpected stimuli. We reported previously that high perceptual load reduces memory accuracy and impairs eyewitness identification. Here, we used eye tracking to investigate whether memory impairments under load are due to inattentional blindness or a failure to visually inspect stimuli. Seventy-two participants viewed high or low load versions of a video depicting a theft and identified characters in the video from photographic line-ups. High perceptual load impaired participants' ability to identify the peripheral character (witness) but not the central character (thief). There was no effect of perceptual load on number of ocular fixations on the witness, time to first fixation or total visit duration. We conclude that memory impairments under load are due to attentional failures rather than differences in visual search behaviour. These findings suggest that high perceptual load scenes may hamper eyewitnesses' ability to encode easily visible stimuli. Copyright © 2017 John Wiley & Sons, Ltd.

We report studies concerning the selective mono-functionalization of 1,1,3,3-tetramethyldisiloxane (TMDSO) with vinyl-substituted silicon derivatives via the hydrosilylation reaction. Examinations of platinum- and rhodium-based catalysts in the reactions between TMDSO and exemplary vinyl-containing silicon derivatives have enabled appointing the most efficient catalyst, whose application leads to selective partial functionalization of the disiloxane reagent and simultaneous formation of only β-regioisomers.

Aim Insulin loses potency when stored at high temperatures. Various clay pots part-filled with water, and other evaporative cooling devices, are used in less-resourced countries when home refrigeration is unavailable. This study examined the cooling efficacy of such devices. Methods Thirteen devices used in Sudan, Ethiopia, Tanzania, Mali, India, Pakistan and Haiti (10 clay pots, a goat skin, a vegetable gourd and a bucket filled with wet sand), and two identical commercially manufactured cooling wallets were compared. Devices were maintained according to local instructions. Internal and ambient temperature and ambient humidity were measured by electronic loggers every 5 min in Khartoum (88 h), and, for the two Malian pots, in Bamako (84 h). Cooling efficacy was assessed by average absolute temperature difference (internal vs. ambient), and % maximal possible evaporative cooling (allowing for humidity). Results During the study period, mean ambient temperature and humidity were 31.0°C and 32.0% in Khartoum and 32.9°C and 39.8% in Bamako. All devices reduced the temperature (P < 0.001) with a mean (sd) reduction from 2.7 ± 0.5°C to 8.3 ± 1.0°C, depending on the device. When expressed as % maximal cooling, device efficacy ranged from 20.5% to 71.3%. On cluster analysis, the most efficacious devices were the goat skin, two clay pots (from Ethiopia and Sudan) and the suspended cooling wallet. Conclusions Low-cost devices used in less-resourced countries reduce storage temperatures. With more efficacious devices, average temperatures at or close to standard room temperature (20–25°C) can be achieved, even in hot climates. All devices are more efficacious at lower humidity. Further studies are needed on insulin stability to determine when these devices are necessary.

BACKGROUND Concerns have been expressed 'that the physician-researcher is a dying breed'. As yet there are few Australian data. AIMS To compare over time: (i) research progress of Sydney Medical School (SMS) medical practitioner - PhD awardees; (ii) National Health and Medical Research Council (NHMRC) project grant success rates for physician-researchers; and (iii) compare current NHMRC, NSW University and NSW Public Hospital pay scales for physician-researchers. METHODS We evaluated 303 medical practitioners awarded a University of Sydney/SMS PhD in 1989-2012 and their publications. We assessed 1990-2014 NHMRC grants to physicians and non-physicians (nationally) and compared physician salaries from NHMRC, the University of Sydney and NSW public hospitals. RESULTS SMS PhD completions by clinicians increased ≈2.4-fold since 1989, with a recent decline, whilst non-medical PhD awardees rose 10-fold. The median time of PhD award after medical degree completion was stable at 13 years. A lower percentage of the more recent physician-researchers had completed specialty training at PhD award (34% in 2011-2012 vs 71% in 1989-1990, P = 0.017). Publication rates were stable, but low. Although NHMRC funding increased >10-fold since 1990, national project grant success rates declined (35% in 1990, 17% in 2013 and 15% in 2014, P < 0.0001), with physician-led funded grants declining from 29% in 1989 to 21% in 2013, P = 0.002. Current NHMRC and University salaries are less than comparable-stage public hospital salaries. CONCLUSION Since 1989, more medical graduates are completing SMS PhDs, although more often prior to completing clinical Fellowships, and many have ongoing, albeit low, research activity. Nationally NHMRC project grant success rates have declined significantly, as has the proportion of funded physician-led projects. Medical practitioner salaries from NHMRC and from Universities are less than in public hospitals. The Australian physician-researcher is at-risk. Knowledge and actions are needed to protect our medical research capacity.

BACKGROUND Given the concerns that physician-researchers are 'at risk', and ≈50% of Australian medical students are female, the evaluation of female physician-researchers is important. AIMS To compare over time (i) research-related metrics of male and female physician-researchers from Sydney Medical School; and (ii) National Health and Medical Research Council (NHMRC) Project grant leadership by gender. METHODS The Sydney Medical School (SMS) PhD award lists from 1989 to 2012 were cross-referenced with the Australian Health Practitioner Regulation Agency database, and registered medical practitioners were searched for in the Scopus database for publications and H-indexes. The gender of medical-practitioner Chief Investigator A (CIA) in Australia on funded NHMRC Project grants in 1990 to 2014 was also compared. RESULTS Of the medical practitioners awarded University of Sydney PhD, females increased from 14 to 55% in 1989-1990 and 2009-2010 and decreased to 38% in 2011-2012 (overall increase, P = 0.047). PhD award timings relative to MBBS and clinical fellowship completions were similar for both genders (P > 0.05). Post-PhD, as many women as men publish and have similar H-indexes, but women publish fewer papers (0.7 vs 1.0 publications per year, P = 0.028). On medical practitioner-led, funded NHMRC project grants between 1999 and 2014, female CIA increased from 7.5 to 19.5%, P

The stabilization of long [n]cumulenes has traditionally been achieved by placing sterically bulky "protecting groups" at the termini, which shield the reactive carbon chain from unwanted reactions. Herein, we present an alternative strategy: stabilization through threading the sp-hybridized carbon chain through a phenanthroline-based macrocycle. The result is stable [9]cumulene rotaxanes that enable the study of properties as a function of length for [n]cumulenes in unprecedented detail, including by quantitative UV/Vis spectroscopy, cyclic voltammetry, and differential scanning calorimetry. The experimental results are supported by DFT calculations.

Die Stabilisierung langer [n]Cumulene wird ublicherweise erreicht, indem sterisch anspruchsvolle “Schutzgruppen” an den Enden angebracht werden, welche die reaktive Kohlenstoffkette abschirmen. Wir stellen hier eine alternative Strategie vor: Stabilisierung durch Einfadeln der sp-Kohlenstoffkette in einen Phenanthrolin-basierten Makrocyclus. Dies fuhrt zu stabilen [9]Cumulen-Rotaxanen, die es uns erlaubten, die Eigenschaften von [n]Cumulenen in Abhangigkeit von ihrer Lange in bis dato unerreichtem Detail zu untersuchen. Dabei nutzten wir quantitative UV/Vis-Spektroskopie, Cyclovoltammetrie und dynamische Differenzkalorimetrie. Die experimentellen Befunde konnen durch DFT-Rechnungen reproduziert und verstanden werden.

Die Verwendung von Cumulenen in chemischen Umsetzungen eroffnet die Moglichkeit, strukturell interessante und potenziell nutzliche konjugierte Molekule herzustellen. Die Cycloadditionsreaktion eines Tetraaryl[5]cumulens mit dem elektronenarmen Olefin Tetracyanoethylen liefert ausergewohnliche Produkte, darunter funktionalisierte Dendralene und Alkylidencyclobutane sowie ein symmetrisches [4]Radialen mit einer besonderen Solvatochromie, dessen λmax-Werte sich dem Nah-IR-Bereich nahern. Diese kohlenstoffreichen Produkte wurden spektroskopisch und rontgenographisch (fur funf der Verbindungen) untersucht. Auch ein moglicher Ablauf der Cycloadditionsreaktion wurde mithilfe mechanistischer und theoretischer Untersuchungen ermittelt. Die Ergebnisse unterstreichen das Potenzial von [5]Cumulenen, als Vorstufen fur neuartige konjugierte Systeme zu dienen.

Diabet. Med. 29, 726–733 (2012) Abstract Objective To determine if ocular and skin autofluorescence, reflecting advanced glycation end-products, and vascular stiffness correlate in non-diabetic and Type 1 diabetic subjects and if levels differ by diabetes status. Research design and methods Patients with Type 1 diabetes (n = 69, 19 with and 50 without vascular complications) and 60 subjects without diabetes (control) had ocular and skin autofluorescence and pulse-wave analysis performed in the fasted state. Correlations between measures within groups used the Pearson or Spearman correlation-coefficient and measures between groups were compared by anova. Results Lens and skin autofluorescence correlated in control (r = 0.58, P = 0.0001) and in Type 1 diabetes (r = 0.53, P = 0.001). Corneal autofluorescence correlated with lens (r = 0.53, r = 0.52, P = 0.0001) and skin autofluorescence (r = 0.34, P = 0.01 and r = 0.49, P = 0.00001) in control and Type 1 diabetes respectively. In Type 1 diabetes, small and large artery elasticity correlated inversely and systemic vascular resistance correlated positively with skin autofluorescence (all P = 0.001), and with lens and corneal autofluorescence (all P

To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress.Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored.PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P0.001; anova between three groups, P0.001], but did not differ significantly between control subjects and complication-free patients (P0.05). In diabetes, PEDF levels correlated (all P0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427).In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.

Characteristic tissue fluorescence is associated with advanced glycation end product (AGE) accumulation in experimental diabetes models, but its utility in patients with type 1 diabetes remains to be established. We studied 148 patients with type 1 diabetes and 77 healthy age-matched control subjects. Low-molecular weight (LMW) fluorophore levels were estimated in plasma samples obtained after an overnight fast. Intra- and interassay coefficients of variation were 4.7% and 6.4%, respectively. LMW fluorophore levels were significantly higher in patients with diabetes than in control subjects (6.3 +/- 0.6 AU/mL vs. 4.1 +/- 0.3; P = 0.007). However, all of this difference came from patients with microvascular complications (n = 67, 7.5 +/- 1.3). There was no significant difference in LMW fluorescence between complication-free patients (4.4 +/- 0.2) and control subjects (P > 0.05). On multivariate analysis, LMW fluorophores correlated with measures of renal function (P < 0.05) but not with diabetes per se. In addition, there was no correlation between LMW fluorophores and the markers of oxidative stress or systemic inflammation. Longitudinal and interventional studies are required to determine whether the association between LMW fluorophores and nephropathy is cause or effect.