State and Local Pension Plans

This paper examines the role and function of pension plans covering state and local government employees in the United States. Covering about 16 million employees (including teachers, fire fighters, police, members of the judiciary, and many other state and local employees), these plans manage a substantial stock of financial assets -- close to $1 trillion -- and receive annual contributions from employees and government revenues totaling about$56 billion. Using data gathered from a variety of different sources, some of which have only recently become available, we describe the benefits, financing, and management of these plans, and identify some of the prominent challenges facing these pension plans in the next decade.

Teaching without boundaries: interviews exploring the adaptation of collaborative inquiry to the American context [version 1; peer review: 2 approved]

Purpose: This study qualitatively examines the efforts of implementing teacher-led collaborative inquiry in American public schools to improve instruction. We focus on a model called Teacher Peer Excellence Group (TPEG), designed to capture the essence of Japanese lesson study and Chinese teaching-study groups that involve lesson planning, peer observations, feedback, and revision. Methods: We conduct qualitative case studies in three pilot schools using a constructivist research paradigm. Findings: We identify action steps essential to introducing and sustaining the TPEG model and pathways to local adaptation. Implications for research and practice: The study contributes to the body of research that seeks to understand the role of instructional leadership and teacher decision-making in successful school-level initiatives

A Comparison of Initial Antiretroviral Therapy in the Swiss HIV Cohort Study and the Recommendations of the International AIDS Society-USA

BACKGROUND: In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS). METHODS: Initial ART regimens prescribed to participants between 1998 and 2007 were classified according to IAS-USA recommendations. Baseline characteristics of patients who received regimens in violation with these recommendations (violation ART) were compared to other patients. Multivariable logistic and linear regression analyses were performed to identify associations between violation ART and (i) virological suppression and (ii) CD4 cell count increase, after one year. RESULTS: Between 1998 and 2007, 4189 SHCS participants started 241 different ART regimens. A violation ART was started in 5% of patients. Female patients (adjusted odds ratio aOR 1.83, 95%CI 1.28-2.62), those with a high education level (aOR 1.49, 95%CI 1.07-2.06) or a high CD4 count (aOR 1.53, 95%CI 1.02-2.30) were more likely to receive violation ART. The proportion of patients with an undetectable viral load (<400 copies/mL) after one year was significantly lower with violation ART than with recommended regimens (aOR 0.54, 95% CI 0.37-0.80) whereas CD4 count increase after one year of treatment was similar in both groups. CONCLUSIONS: Although more than 240 different initial regimens were prescribed, violations of the IAS-USA recommendations were uncommon. Patients receiving these regimens were less likely to have an undetectable viral load after one year, which strengthens the validity of these recommendations

Association of alpha-aminoadipic acid with cardiometabolic risk factors in healthy and high-risk individuals

IntroductionPlasma levels of the metabolite alpha-aminoadipic acid (2-AAA) have been associated with risk of type 2 diabetes (T2D) and atherosclerosis. However, little is known about the relationship of 2-AAA to other cardiometabolic risk markers in pre-disease states, or in the setting of comorbid disease.MethodsWe measured circulating 2-AAA using two methods in 1) a sample of 261 healthy individuals (2-AAA Study), and 2) in a sample of 134 persons comprising 110 individuals with treated HIV, with or without T2D, a population at high risk of metabolic disease and cardiovascular events despite suppression of circulating virus, and 24 individuals with T2D without HIV (HATIM Study). We examined associations between plasma 2-AAA and markers of cardiometabolic health within each cohort.Results and discussionWe observed differences in 2-AAA by sex and race in both cohorts, with higher levels observed in men compared with women, and in Asian compared with Black or white individuals (P&lt;0.05). There was no significant difference in 2-AAA by HIV status within individuals with T2D in the HATIM Study. We confirmed associations between 2-AAA and dyslipidemia in both cohorts, where high 2-AAA associated with low HDL cholesterol (P&lt;0.001) and high triglycerides (P&lt;0.05). As expected, within the cohort of people with HIV, 2-AAA was higher in the setting of T2D compared to pre-diabetes or normoglycemia (P&lt;0.001). 2-AAA was positively associated with body mass index (BMI) in the 2-AAA Study, and with waist circumference and measures of visceral fat volume in HATIM (all P&lt;0.05). Further, 2-AAA associated with increased liver fat in persons with HIV (P&lt;0.001). Our study confirms 2-AAA as a marker of cardiometabolic risk in both healthy individuals and those at high cardiometabolic risk, reveals relationships with adiposity and hepatic steatosis, and highlights important differences by sex and race. Further studies are warranted to establish molecular mechanisms linking 2-AAA to disease in other high-risk populations

Nasopharyngeal Pneumococcal Colonization Density Is Associated With Severe Pneumonia in Young Children in the Lao People's Democratic Republic

BACKGROUND: No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization (WHO) 2013 definition. In Lao People's Democratic Republic (Lao PDR), we determine the association between nasopharyngeal pneumococcal density and severe pneumonia in children. METHODS: A prospective observational study was undertaken at Mahosot Hospital, Vientiane, from 2014 to mid-2018. Children <5 years admitted with acute respiratory infections (ARIs) were included. Clinical and demographic data were collected alongside nasopharyngeal swabs for pneumococcal quantification by lytA real-time quantitative polymerase chain reaction. Severe pneumonia was defined using the 2013 WHO definition. For pneumococcal carriers, a logistic regression model examined the association between pneumococcal density and severe pneumonia, after adjusting for potential confounders including demographic and household factors, 13-valent pneumococcal conjugate vaccine status, respiratory syncytial virus co-detection, and preadmission antibiotics. RESULTS: Of 1268 participants with ARI, 32.3% (n = 410) had severe pneumonia and 36.9% (n = 468) had pneumococcal carriage. For pneumococcal carriers, pneumococcal density was positively associated with severe pneumonia (adjusted odds ratio, 1.4 [95% confidence interval, 1.1-1.8]; P = .020). CONCLUSIONS: Among children with ARIs and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Lao PDR. Further studies may determine if pneumococcal density is a useful marker for pneumococcal conjugate vaccine impact on childhood pneumonia

Progress with the Prime Focus Spectrograph for the Subaru Telescope: a massively multiplexed optical and near-infrared fiber spectrograph

The Prime Focus Spectrograph (PFS) is an optical/near-infrared multi-fiber spectrograph with 2394 science fibers, which are distributed in 1.3 degree diameter field of view at Subaru 8.2-meter telescope. The simultaneous wide wavelength coverage from 0.38 um to 1.26 um, with the resolving power of 3000, strengthens its ability to target three main survey programs: cosmology, Galactic archaeology, and galaxy/AGN evolution. A medium resolution mode with resolving power of 5000 for 0.71 um to 0.89 um also will be available by simply exchanging dispersers. PFS takes the role for the spectroscopic part of the Subaru Measurement of Images and Redshifts project, while Hyper Suprime-Cam works on the imaging part. To transform the telescope plus WFC focal ratio, a 3-mm thick broad-band coated glass-molded microlens is glued to each fiber tip. A higher transmission fiber is selected for the longest part of cable system, while one with a better FRD performance is selected for the fiber-positioner and fiber-slit components, given the more frequent fiber movements and tightly curved structure. Each Fiber positioner consists of two stages of piezo-electric rotary motors. Its engineering model has been produced and tested. Fiber positioning will be performed iteratively by taking an image of artificially back-illuminated fibers with the Metrology camera located in the Cassegrain container. The camera is carefully designed so that fiber position measurements are unaffected by small amounts of high special-frequency inaccuracies in WFC lens surface shapes. Target light carried through the fiber system reaches one of four identical fast-Schmidt spectrograph modules, each with three arms. Prototype VPH gratings have been optically tested. CCD production is complete, with standard fully-depleted CCDs for red arms and more-challenging thinner fully-depleted CCDs with blue-optimized coating for blue arms.Comment: 14 pages, 12 figures, submitted to "Ground-based and Airborne Instrumentation for Astronomy V, Suzanne K. Ramsay, Ian S. McLean, Hideki Takami, Editors, Proc. SPIE 9147 (2014)

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it