Pensions and the Labor Market

Employers typically view their investment in pension plans as a means of providing retirement income for their workers. Economists, on the other hand, view pension programs as a way to increase workplace productivity. Dorsey, Cornwell and Macpherson explore the theoretical and empirical basis for this perspective and, in the process, offer a complete and up-to-date discussion on the productivity theory of pensions.https://research.upjohn.org/up_press/1067/thumbnail.jp

Pensions and Productivity

Employers typically view their investment in pension plans as a means of providing retirement income for their workers. Economists, on the other hand, view pension programs as a way to increase workplace productivity. Dorsey, Cornwell and Macpherson explore the theoretical and empirical basis for this perspective and, in the process, offer a complete and up-to-date discussion on the productivity theory of pensions.https://research.upjohn.org/up_press/1067/thumbnail.jp

Origin and evolution of the slab fluids since subduction inception in the Izu-Bonin-Mariana: A comparison with the southeast Mariana fore-arc rift

Subduction zones have played a central role in exchanging volatiles (H2O, CO2, S, halogens) between the different Earth's reservoirs throughout its history. Fluids that are released as the subducted plates dehydrate are major agents that transfer these volatiles inside the Earth; but the origins and the compositional evolution of the slab fluids as plates begin to sink are yet to be understood. To explore processes that take place during subduction infancy, here we examine the compositions of proto-arc magmas from the Izu-Bonin-Mariana (IBM) convergent margin that formed during subduction inception; and we compare these to a modern example of near-trench spreading in the southeast Mariana fore-arc rift (SEMFR). There is a temporal and spatial evolution in the slab fluid composition that is accompanied with a change in the fluid reservoirs, as subduction progresses. During the early stages of the subduction zone, dehydration of the serpentinized subducting mantle likely triggered dehydration and melting of the altered oceanic crust in the amphibolite facies to produce boninites. As the subduction zone matured, the volcanic arc front was displaced away from the trench. The arc magmas captured deeper slab fluids released from the subducted oceanic crust, the sediments and the underlying serpentinized mantle. Dehydration and melting of the subducted sediment became more prevalent with time and increasing slab depth ( ≥ 100 km) to produce arc magmas. This compositional evolution was associated with a deepening of magma generation, which is likely accompanied with the progressive serpentinization of fore-arc mantle. Hence, fore-arc mantle serpentinization might have facilitated arc maturation and subduction stabilization throughout the IBM history

Model free audit methodology for bias evaluation of tumour progression in oncology

Many oncology studies incorporate a blinded independent central review (BICR) to make an assessment of the integrity of the primary endpoint, progression free survival. Recently, it has been suggested that, in order to assess the potential for bias amongst investigators, a BICR amongst only a sample of patients could be performed; if evidence of bias is detected, according to a predefined threshold, the BICR is then assessed in all patients, otherwise, it is concluded that the sample was sufficient to rule out meaningful levels of bias. In this paper, we present an approach that adapts a method originally created for defining futility bounds in group sequential designs. The hazard ratio ratio, the ratio of the hazard ratio (HR) for the treatment effect estimated from the BICR to the corresponding HR for the investigator assessments, is used as the metric to define bias. The approach is simple to implement and ensures a high probability that a substantial true bias will be detected. In the absence of bias, there is a high probability of accepting the accuracy of local evaluations based on the sample, in which case an expensive BICR of all patients is avoided. The properties of the approach are demonstrated by retrospective application to a completed Phase III trial in colorectal cancer. The same approach could easily be adapted for other disease settings, and for test statistics other than the hazard ratio.</p

Evidence of cross-cutting and redox reaction in Khatyrka meteorite reveals metallic-Al minerals formed in outer space

We report on a fragment of the quasicrystal-bearing CV3 carbonaceous chondrite Khatyrka recovered from fine-grained, clay-rich sediments in the Koryak Mountains, Chukotka (Russia). We show higher melting-point silicate glass cross-cutting lower melting-point Al-Cu-Fe alloys, as well as unambiguous evidence of a reduction-oxidation reaction history between Al-Cu-Fe alloys and silicate melt. The redox reactions involve reduction of FeO and SiO_2 to Fe and Fe-Si metal, and oxidation of metallic Al to Al_2O_3, occurring where silicate melt was in contact with Al-Cu-Fe alloys. In the reaction zone, there are metallic Fe and Fe-Si beads, aluminous spinel rinds on the Al-Cu-Fe alloys, and Al_2O_3 enrichment in the silicate melt surrounding the alloys. From this and other evidence, we demonstrate that Khatyrka must have experienced at least two distinct events: first, an event as early as 4.564 Ga in which the first Al-Cu-Fe alloys formed; and, second, a more recent impact-induced shock in space that led to transformations of and reactions between the alloys and the meteorite matrix. The new evidence firmly establishes that the Al-Cu-Fe alloys (including quasicrystals) formed in outer space in a complex, multi-stage process

Peripheral Administration of the Soluble TNF Inhibitor XPro1595 Modifies Brain Immune Cell Profiles, Decreases Beta-Amyloid Plaque Load, and Rescues Impaired Long-Term Potentiation in 5xFAD Mice

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer’s disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII+, CD45high, and Ly6Chigh) myeloid-derived CD11b+ immune cells are decreased while CD3+ T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4+ T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. &lt;p/&gt;Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). &lt;p/&gt;Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. &lt;p/&gt;Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Tower and Aircraft Eddy Covariance Measurements of Water Vapor, Energy, and Carbon Dioxide Fluxes during SMACEX

Abstract A network of eddy covariance (EC) and micrometeorological flux (METFLUX) stations over corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] canopies was established as part of the Soil Moisture–Atmosphere Coupling Experiment (SMACEX) in central Iowa during the summer of 2002 to measure fluxes of heat, water vapor, and carbon dioxide (CO2) during the growing season. Additionally, EC measurements of water vapor and CO2 fluxes from an aircraft platform complemented the tower-based measurements. Sensible heat, water vapor, and CO2 fluxes showed the greatest spatial and temporal variability during the early crop growth stage. Differences in all of the energy balance components were detectable between corn and soybean as well as within similar crops throughout the study period. Tower network–averaged fluxes of sensible heat, water vapor, and CO2 were observed to be in good agreement with area-averaged aircraft flux measurements

HIV coinfection influences the inflammatory response but not the outcome of cerebral malaria in Malawian children

This work was supported by grants from the NIH (T.E.T., 5R01AI034969-14) and a Clinical Fellowship from The Wellcome Trust, United Kingdom (C.A.M, 88758). The Malawi-Liverpool-Wellcome Clinical Research Programme is supported by core funding from The Wellcome Trust, UK.Objectives. Study of the effect of HIV on disease progression in heterogeneous severe malaria syndromes with imprecise diagnostic criteria has led to varying results. Characteristic retinopathy refines cerebral malaria (CM) diagnosis, enabling more precise exploration of the hypothesis that HIV decreases the cytokine response in CM, leading to higher parasite density and a poor outcome. Methods. We retrospectively reviewed data on clinical progression and laboratory parameters in 877 retinopathy-positive CM cases admitted 1996-2011 (14.4% HIV-infected) to a large hospital in Malawi. Admission plasma levels of TNF, interleukin-10, and soluble intercellular adhesion molecule (sICAM-1) were measured by ELISA in 135 retinopathy-positive CM cases. Results. HIV-infected CM cases had lower median plasma levels of TNF (p=0.008), interleukin-10 (p=0.045) and sICAM-1 (p=0.04) than HIV-uninfected cases. Although HIV-infected children were older and more likely to have co-morbidities, HIV-status did not significantly affect parasite density (p=0.90) or outcome (24.8% infected, vs. 18.5% uninfected; p=0.13). Conclusions. In this well-characterised CM cohort, HIV-coinfection was associated with marked blunting of the inflammatory response but did not affect parasite density or outcome. These data highlight the complex influence of HIV on severe malaria and bring into question systemic inflammation as a primary driver of pathogenesis in human CM.Publisher PDFPeer reviewe

Development of a patient decision aid for children and adolescents following anterior cruciate ligament rupture: an international mixed-methods study

AIM: To develop and user test an evidence-based patient decision aid for children and adolescents who are considering anterior cruciate ligament (ACL) reconstruction.DESIGN: Mixed-methods study describing the development of a patient decision aid.SETTING: A draft decision aid was developed by a multidisciplinary steering group (including various types of health professionals and researchers, and consumers) informed by the best available evidence and existing patient decision aids.PARTICIPANTS: People who ruptured their ACL when they were under 18 years old (ie, adolescents), their parents, and health professionals who manage these patients. Participants were recruited through social media and the network outreach of the steering group.PRIMARY AND SECONDARY OUTCOMES: Semistructured interviews and questionnaires were used to gather feedback on the decision aid. The feedback was used to refine the decision aid and assess acceptability. An iterative cycle of interviews, refining the aid according to feedback and further interviews, was used. Interviews were analysed using reflexive thematic analysis.RESULTS: We conducted 32 interviews; 16 health professionals (12 physiotherapists, 4 orthopaedic surgeons) and 16 people who ruptured their ACL when they were under 18 years old (7 were adolescents and 9 were adults at the time of the interview). Parents participated in 8 interviews. Most health professionals, patients and parents rated the aid's acceptability as good-to-excellent. Health professionals and patients agreed on most aspects of the decision aid, but some health professionals had differing views on non-surgical management, risk of harms, treatment protocols and evidence on benefits and harms.CONCLUSION: Our patient decision aid is an acceptable tool to help children and adolescents choose an appropriate management option following ACL rupture with their parents and health professionals. A clinical trial evaluating the potential benefit of this tool for children and adolescents considering ACL reconstruction is warranted.</p