99 research outputs found

    The not-for-profit form and translational research: Kerr revisited?

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    Translational research conducted in academic health centers is confounded by the organizational structure in which the work is performed. Investigators must obtain research funding and appropriate recognition as a part of a research team in a not-for-profit environment which has more readily rewarded basic work, and individual accomplishments. What results is a unique form of conflict of interest, best understood by relating the basic principles underlying the not-for-profit form to the conduct of translational research in the AHC setting

    The \u3cem\u3eToxoplasma gondii\u3c/em\u3e Protein ROP2 Mediates Host Organelle Association with the Parasitophorous Vacuole Membrane

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    Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH2-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is partially translocated into the mitochondrial outer membrane and behaves like an integral membrane protein. Although ROP2hc does not translocate across the ER membrane, it does exhibit carbonate-resistant binding to this organelle. In vivo, ROP2hc expressed as a soluble fragment in the cytosol of uninfected cells associates with both mitochondria and ER. The 30–amino acid (aa) NH2-terminal sequence of ROP2hc, when fused to green fluorescent protein (GFP), is sufficient for mitochondrial targeting. Deletion of the 30-aa NH2-terminal signal from ROP2hc results in robust localization of the truncated protein to the ER. These results demonstrate a new mechanism for tight association of different membrane-bound organelles within the cell cytoplasm

    The Toxoplasma gondii protein ROP2 mediates host organelle association with the parasitophorous vacuole membrane

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    Toxoplasma gondii replicates within a specialized vacuole surrounded by the parasitophorous vacuole membrane (PVM). The PVM forms intimate interactions with host mitochondria and endoplasmic reticulum (ER) in a process termed PVM–organelle association. In this study we identify a likely mediator of this process, the parasite protein ROP2. ROP2, which is localized to the PVM, is secreted from anterior organelles termed rhoptries during parasite invasion into host cells. The NH2-terminal domain of ROP2 (ROP2hc) within the PVM is exposed to the host cell cytosol, and has characteristics of a mitochondrial targeting signal. In in vitro assays, ROP2hc is partially translocated into the mitochondrial outer membrane and behaves like an integral membrane protein. Although ROP2hc does not translocate across the ER membrane, it does exhibit carbonate-resistant binding to this organelle. In vivo, ROP2hc expressed as a soluble fragment in the cytosol of uninfected cells associates with both mitochondria and ER. The 30–amino acid (aa) NH2-terminal sequence of ROP2hc, when fused to green fluorescent protein (GFP), is sufficient for mitochondrial targeting. Deletion of the 30-aa NH2-terminal signal from ROP2hc results in robust localization of the truncated protein to the ER. These results demonstrate a new mechanism for tight association of different membrane-bound organelles within the cell cytoplasm

    Secretory traffic in the eukaryotic parasite Toxoplasma gondii: less is more

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    Name a single-celled eukaryote that boasts a small genome size, is easily cultivated in haploid form, for which a wide variety of molecular genetic tools are available, and that exhibits a simple, polarized secretory apparatus with a well-defined endoplasmic reticulum and Golgi that can serve as a model for understanding secretion. Got it? Now name a cell with all these attributes that contains at least a dozen distinct and morphologically well-defined intracellular organelles, including three distinct types of secretory vesicles and two endosymbiotic organelles. Not so sure anymore

    Indemnifying Precaution: Economic Insights for Regulation of a Highly Infectious Disease

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    Economic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing. One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions. Without legal intervention, some individuals will see socially risky behaviors as personally less costly than socially beneficial behaviors, a balance that makes those beneficial behaviors unsustainable. For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing noncompliant people are stymied. One mechanism is for policymakers to indemnify individuals for losses associated with taking those socially desirable behaviors to reduce the spread. We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms

    A Randomized Experiment of the Split Benefit Health Insurance Reform to Reduce High-Cost, Low-Value Consumption

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    Traditional cost sharing for health care is stymied by limited patient wealth. The “split benefit” is a new way to reduce consumption of high-cost, low-value treatments for which the risk/benefit ratio is uncertain. When a physician prescribes a costly unproven procedure, the insurer could pay a portion of the benefit directly to the patient, creating a decision opportunity for the patient. The insurer saves the remainder, unless the patient consumes. In this paper, a vignette-based randomized controlled experiment with 1,800 respondents sought to test the potential efficacy of the split benefit. The intervention reduced the odds of consumption by about half. It did so regardless of scenario (cancer or cardiac stent), type of split (rebate, prepay, or health savings account), or amount of split (US5,000orUS5,000 or US15,000). Respondents viewed the insurer that paid a split as behaving fairly, as it preserved access and choice. Three-quarters of respondents supported such use in Medicare, which did not depend on political party affiliation. The reform is promising for further testing since it has the potential to decrease spending on low-value interventions, and thereby increase the value of the health care dollar

    Is your training service resilient and postured to support organisational sustainment?

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    Organisations increasingly invest in resilience to better deal with future uncertainties and change. An organisation’s training service is one of the critical ingredients of this effort. However, its role in posturing organisational sustainment in a volatile operational environment and organisational resilience-building effort is rarely considered in its own right and often overlooked. This paper reports developing, verifying, and validating a new survey instrument for assessing the resilience performance of the organisation’s training systems. The instrument is based on six resilience attributes juxtaposing organisational ability and capacity to allow management to compare its resilience expectations with the actual resilience and make trade- off decisions. The efficacy of the training service policy is also considered to enable appropriate attribution of the survey findings to the training policy issues or its poor implementation. The survey incorporated a robust mixed-method, multi-attribute and multi- perspective approach that has been applied extensively with 1,403 respondents from more than 20 military training establishments over three years. This research provides organisational leadership with a focused diagnostic instrument in their training aspects’ performance against resilience metrics, where such training aspects are often a dynamic enabler for change and, thus, overall organisational sustainability and evolutionary competitiveness

    Does Hospital Electronic Medical Record Adoption Lead To Upcoding or More Accurate Coding?

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    Abstract This paper seeks to evaluate whether the adoption of electronic medical records (EMRs) leads to upcoding for hospitalized Medicare patients, defined as categorizing a condition as more serious than justified in order to inflate bills, or more accurate coding. We use a triple difference: (1) between EMR and non-EMR hospitals; (2) before and after the 2007 Medicare payment reform, which made obtaining high payments harder; and (3) between medical and surgical admissions. For medical admissions, we find that the interaction of Medicare payment reform and EMR hospitals leads to higher codes, regardless of the financial incentive to upcode. For surgical admissions, we find no significant effect. While there is no evidence of upcoding, EMRs lead to higher billing by increasing the accuracy of coding for medical admissions

    The association between life events And suicide intent in self-poisoners with and without a history of deliberate self-harm: a preliminary study.

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    The associations between life events in the 12 months preceding an episode of self-poisoning resulting in hospital attendance (the index episode), and the suicide intent of this episode were compared in individuals for whom the index episode was their first, episode and in individuals in whom it was a recurrence of DSH. Results indicated a significant interaction between independent life events, repetition status, and gender in the prediction of suicide intent, the association between life events and intent being moderated by repetition status in women only. The results provide preliminary evidence to suggest the presence of a suicidal process in women, in which the impact of negative life events on suicide intent diminishes across episodes
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