Applying economic principles to health care.

Applying economic thinking to an understanding of resource use in patient care is challenging given the complexities of delivering health care in a hospital. Health-care markets lack the characteristics needed to determine a "market" price that reflects the economic value of resources used. However, resource allocation in a hospital can be analyzed by using production theory to determine efficient resource use. The information provided by hospital epidemiologists is critical to understanding health-care production processes used by a hospital and developing economic incentives to promote antibiotic effectiveness and infection control

Helium Nova on a Very Massive White Dwarf -- A Light Curve Model of V445 Puppis (2000) Revised

V445 Pup (2000) is a unique object identified as a helium nova. Color indexes during the outburst are consistent with those of free-free emission. We present a free-free emission dominated light curve model of V445 Pup on the basis of the optically thick wind theory. Our light curve fitting shows that (1) the white dwarf (WD) mass is very massive (M_WD \gtrsim 1.35 M_\sun), and (2) a half of the accreted matter remains on the WD, both of which suggest that the increasing WD mass. Therefore, V445 Pup is a strong candidate of Type Ia supernova progenitor. The estimated distance to V445 Pup is now consistent with the recent observational suggestions, 3.5 < d < 6.5 kpc. A helium star companion is consistent with the brightness of m_v=14.5 mag just before the outburst, if it is a little bit evolved hot (\log T (K) \gtrsim 4.5) star with the mass of M_He \gtrsim 0.8 M_\sun. We then emphasize importance of observations in the near future quiescent phase after the thick circumstellar dust dissipates away, especially its color and magnitude to specify the nature of the companion star. We have also calculated helium ignition masses for helium shell flashes against various helium accretion rates and discussed the recurrence period of helium novae.Comment: 8 pages including 12 figures, to appear in Ap

XMM-Newton Observations of PSR B1706-44

We report on the XMM-Newton observations of the young, 102 ms pulsar PSR B1706-44. We have found that both a blackbody plus power-law and a magnetized atmospheric model plus power-law provide an excellent fit to the EPIC spectra. The two scenarios are therefore indistinguishable on a statistical basis, although we are inclined to prefer the latter on physical grounds. In this case, assuming a source distance of ~2.3 kpc, the size of the region responsible for the thermal emission is R~13 km, compatible with the surface of a neutron star. A comparison of the surface temperature of PSR B1706-44 obtained from this fit with cooling curves favor a medium mass neutron star with M~1.45 solar masses or M~1.59 solar masses, depending on two different models of proton superfluidity in the interior. The large collecting area of XMM-Newton allows us to resolve a substructure in the broad soft X-ray modulation detected by Chandra, revealing the presence of two separate peaks with pulsed fractions of 7 +/- 4% and 15 +/- 3%, respectively.Comment: 21 pages, 5 figures, 2 tables, accepted for publication in Ap

PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges

© 2019 The Authors Unprecedented efficacy of chimeric antigen receptor (CAR) T cell therapy in the treatment of hematologic malignancies brings new hope for patients with many cancer types including solid tumors. However, the challenges for CAR-T cell therapy in eradicating solid tumors are immense. To overcome these seemingly intractable hurdles, more “powerful” CAR-T cells with enhanced antitumor efficacy are required. Emerging data support that the anti-tumor activity of CAR-T cells can be enhanced significantly without evident toxicity through simultaneous PD-1 disruption by genome editing. This review focuses on the current progress of PD-1 gene disrupted CAR-T cells in cancer therapy. Here we discuss key rationales for this new combination strategy and summarize the available pre-clinical studies. An update is provided on human clinical studies and available registered cancer clinical trials using CAR-T cells with PD-1 disruption. Future prospects and challenges are also discussed

Cell-penetrating peptides containing the progesterone receptor polyproline domain inhibits EGF signaling and cell proliferation in lung cancer cells.

Non-small cell lung cancer (NSCLC) accounts for the majority (80-85%) of all lung cancers. All current available treatments have limited efficacy. The epidermal growth factor receptor (EGFR) plays a critical role in the development and progression of NSCLC, with high EGFR expression associated with increased cell proliferation and poor prognosis. Thus, interfering with EGFR signaling has been shown to effectively reduce cell proliferation and help in the treatment of NSCLC. We previously demonstrated that the progesterone receptor (PR) contains a polyproline domain (PPD) that directly interacts with Src homology 3 (SH3) domain-containing molecules and expression of PR-PPD peptides inhibits NSCLC cell proliferation. In this study, we investigated whether the introduction of PR-PPD by cell-penetrating peptides (CPPs) could inhibit EGF-induced cell proliferation in NSCLC cells. PR-PPD was attached to a cancer-specific CPP, Buforin2 (BR2), to help deliver the PR-PPD into NSCLC cells. Interestingly, addition of BR2-2xPPD peptides containing two PR-PPD repeats was more effective in inhibiting NSCLC proliferation and significantly reduced EGF-induced phosphorylation of Erk1/2. BR2-2xPPD treatment induced cell cycle arrest by inhibiting the expression of cyclin D1 and CDK2 genes in EGFR-wild type A549 cells. Furthermore, the combination treatment of EGFR-tyrosine kinase inhibitors (TKIs), including Gefitinib or Erlotinib, with BR2-2xPPD peptides further suppressed the growth of NSCLC PC9 cells harboring EGFR mutations as compared to EGFR-TKIs treatment alone. Importantly, BR2-2xPPD peptides mediated growth inhibition in acquired Gefitinib- and Erlotinib- resistant lung adenocarcinoma cells. Our data suggests that PR-PPD is the minimal protein domain sufficient to inhibit NSCLC cell growth and has the potential to be developed as a novel NSCLC therapeutic agent

Probing the Pulsar Wind Nebula of PSR B0355+54

We present XMM-Newton and Chandra X-ray observations of the middle-aged radio pulsar PSR B0355+54. Our X-ray observations reveal emission not only from the pulsar itself, but also from a compact diffuse component extending ~50'' in the opposite direction to the pulsar's proper motion. There is also evidence for the presence of fainter diffuse emission extending ~5' from the point source. The compact diffuse feature is well-fitted with a power-law, the index of which is consistent with the values found for other pulsar wind nebulae. The morphology of the diffuse component is similar to the ram-pressure confined pulsar wind nebulae detected for other sources. The X-ray emission from the pulsar itself is described well by a thermal plus power-law fit, with the thermal emission most likely originating in a hot polar cap.Comment: 9 pages (uses emulateapj.cls), 8 figures, 2 tables, accepted for publication in Ap

Examining the effectiveness of place-based interventions to improve public health and reduce health inequalities: an umbrella review.

BackgroundLocally delivered, place-based public health interventions are receiving increasing attention as a way of improving health and reducing inequalities. However, there is limited evidence on their effectiveness. This umbrella review synthesises systematic review evidence of the health and health inequalities impacts of locally delivered place-based interventions across three elements of place and health: the physical, social, and economic environments.MethodsSystematic review methodology was used to identify recent published systematic reviews of the effectiveness of place-based interventions on health and health inequalities (PROGRESS+) in high-income countries. Nine databases were searched from 1st January 2008 to 1st March 2020. The quality of the included articles was determined using the Revised Assessment of Multiple Systematic Reviews tool (R-AMSTAR).ResultsThirteen systematic reviews were identified - reporting 51 unique primary studies. Fifty of these studies reported on interventions that changed the physical environment and one reported on changes to the economic environment. Only one primary study reported cost-effectiveness data. No reviews were identified that assessed the impact of social interventions. Given heterogeneity and quality issues, we found tentative evidence that the provision of housing/home modifications, improving the public realm, parks and playgrounds, supermarkets, transport, cycle lanes, walking routes, and outdoor gyms - can all have positive impacts on health outcomes - particularly physical activity. However, as no studies reported an assessment of variation in PROGRESS+ factors, the effect of these interventions on health inequalities remains unclear.ConclusionsPlace-based interventions can be effective at improving physical health, health behaviours and social determinants of health outcomes. High agentic interventions indicate greater improvements for those living in greater proximity to the intervention, which may suggest that in order for interventions to reduce inequalities, they should be implemented at a scale commensurate with the level of disadvantage. Future research needs to ensure equity data is collected, as this is severely lacking and impeding progress on identifying interventions that are effective in reducing health inequalities.Trial registrationPROSPERO CRD42019158309

Cardiac disorders and structural brain abnormalities are commonly associated with hypospadias in children with neurodevelopmental disorders

Ther objective of our study was to use an established cohort of boys to investigate common patterns of malformations in those with hypospadias. We performed a retrospective review of the phenotype of participants in the Deciphering Developmental Disorders Study with neurodevelopmental delay and an 'Abnormality of the genital system'. This group was divided into two subgroups: those with hypospadias and without hypospadias. Associated phenotypes of the two subgroups were compared and analysed. Of the 166 Deciphering Developmental Disorders participants with hypospadias and neurodevelopmental delay, 47 (28%) had cardiovascular and 40 (24%) had structural brain abnormalities. The rate of cardiovascular abnormalities in those with neurodevelopmental delay and genital abnormalities other than hypospadias (N = 645) was lower at 19% (P = 0.001). In addition, structural brain malformations were higher at 24% in the hypospadias group versus 15% in the group without hypospadias (P = 0.002). The constellation of these features occured at a higher rate in the hypospadias group versus the no hypospadias group (P = 0.038). In summary, this is the first study to indicate that cardiovascular and brain abnormalities are frequently encountered in association with hypospadias in children with neurodevelopmental disorders. Not only do these associations provide insight into the underlying aetiology but also they highlight the multisystem involvement in conditions with hypospadias

Long-term perspectives on terrestrial and aquatic carbon cycling from palaeolimnology

Lakes are active processors and collectors of carbon (C) and thus recognized as quantitatively important within the terrestrial C cycle. Better integration of palaeolimnology (lake sediment core analyses) with limnological C budgeting approaches has the potential to enhance understanding of lacustrine C processing and sequestration. Palaeolimnology simultaneously assimilates materials from across lake habitats, terrestrial watersheds, and airsheds to provide a uniquely broad overview of the terrestrial-atmospheric-aquatic linkages across different spatial scales. The examination of past changes over decadal–millennial timescales via palaeolimnology can inform understanding and prediction of future changes in C cycling. With a particular, but not exclusive, focus on northern latitudes we examine the methodological approaches of palaeolimnology, focusing on how relatively standard and well-tested techniques might be applied to address questions of relevance to the C cycle. We consider how palaeolimnology, limnology, and sedimentation studies might be linked to provide more quantitative and holistic estimates of lake C cycling and budgets. Finally, we use palaeolimnological examples to consider how changes such as terrestrial vegetation shifts, permafrost thaw, the formation of new lakes and reservoirs, hydrological modification of inorganic C processing, land use change, soil erosion and disruption to global nitrogen and phosphorus cycles might influence lake C cycling