Managing Customization in Health Care: A Framework Derived from the Services Sector Literature

Organizations that provide health services are increasingly in need of systems and approaches that will enable them to be more responsive to the needs and wishes of their clients. Two recent trends, namely, patient-centered care (PCC) and personalized medicine, are first steps in the customization of care. PCC shifts the focus away from the disease to the patient. Personalized medicine, which relies heavily on genetics, promises significant improvements in the quality of healthcare through the development of tailored and targeted drugs. We need to understand how these two trends can be related to customization in healthcare delivery and, because customization often entails extra costs, to define new business models. This article analyze how customization of the care process can be developed and managed in healthcare. Drawing on relevant literature from various services sectors, we have developed a framework for the implementation of customization by the hospital managers and caregivers involved in care pathways

Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1 to S phase transition and identifies a conserved family of proteins

Regulation of cell cycle progression occurs in part through the targeted degradation of both activating and inhibitory subunits of the cyclin-dependent kinases. During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the destruction of these regulators. Here we describe evidence indicating that CDC53 also is involved in this process. Mutations in CDC53 cause a phenotype indistinguishable from those of cdc4 and cdc34 mutations, numerous genetic interactions are seen between these genes, and the encoded proteins are found physically associated in vivo. Cdc53p defines a large family of proteins found in yeasts, nematodes, and humans whose molecular functions are uncharacterized. These results suggest a role for this family of proteins in regulating cell cycle proliferation through protein degradation

Energetics and thermal adaptation in semifossorial pine-voles Microtus lusitanicus and Microtus duodecimcostatus

Acknowledgments are due for the financial support to Centre for environment and marine studies (UID/AMB/50017-POCI-01-0145-FEDER-007638), to Fundação para a Ciência e Tecnologia through national funds (PIDDAC), and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. RIM was supported by fellowship BPD/UI88/7346/2016 and JRS was supported by the 1000 talents program of the Chinese government. We thank the three anonymous referees for their valuable comments on this manuscript.Peer reviewedPostprin

Deficiency of GABAergic synaptic inhibition in the Kölliker-Fuse area underlies respiratory dysrhythmia in a mouse model of Rett syndrome

Life threatening breathing irregularity and central apnoeas are highly prevalent in children suffering from Rett syndrome. Abnormalities in inhibitory synaptic transmission have been associated with the physiopathology of this syndrome, and may underlie the respiratory disorder. In a mouse model of Rett syndrome, GABAergic terminal projections are markedly reduced in the Kölliker–Fuse nucleus (KF) in the dorsolateral pons, an important centre for control of respiratory rhythm regularity. Administration of a drug that augments endogenous GABA localized to this region of the pons reduced the incidence of apnoea and the respiratory irregularity of Rett female mice. Conversely, the respiratory disorder was recapitulated by blocking GABAergic transmission in the KF area of healthy rats. This study helps us understand the mechanism for generation of respiratory abnormality in Rett syndrome, pinpoints a brain site responsible and provides a clear anatomical target for the development of a translatable drug treatment

Toward scalable biocatalytic conversion of 5-hydroxymethylfurfural by galactose oxidase using coordinated reaction and enzyme engineering

5-Hydroxymethylfurfural (HMF) can be transformed to a range of industrially useful derivatives, such as 2,5-diformylfuran (DFF), but the reactions needed for efficient industrial production are hindered by several issues. Here, the authors perform reaction and enzyme engineering resulting in a galactose oxidase variant with high activity towards HMF, improved oxygen binding and high productivity

Genetic Overlap Profiles of Cognitive Ability in Psychotic and Affective Illnesses: A Multisite Study of Multiplex Pedigrees

Background: Cognitive impairment is a key feature of psychiatric illness, making cognition an important tool for exploring of the genetics of illness risk. It remains unclear which measures should be prioritized in pleiotropy-guided research. Here, we generate profiles of genetic overlap between psychotic and affective disorders and cognitive measures in Caucasian and Hispanic groups. Methods: Data were from 4 samples of extended pedigrees (N = 3046). Coefficient of relationship analyses were used to estimate genetic overlap between illness risk and cognitive ability. Results were meta-analyzed. Results: Psychosis was characterized by cognitive impairments on all measures with a generalized profile of genetic overlap. General cognitive ability shared greatest genetic overlap with psychosis risk (average endophenotype ranking value [ERV] across samples from a random-effects meta-analysis = 0.32), followed by verbal memory (ERV = 0.24), executive function (ERV = 0.22), and working memory (ERV = 0.21). For bipolar disorder, there was genetic overlap with processing speed (ERV = 0.05) and verbal memory (ERV = 0.11), but these were confined to select samples. Major depressive disorder was characterized by enhanced working and face memory performance, as reflected in significant genetic overlap in 2 samples. Conclusions: There is substantial genetic overlap between risk for psychosis and a range of cognitive abilities (including general intelligence). Most of these effects are largely stable across of ascertainment strategy and ethnicity. Genetic overlap between affective disorders and cognition, on the other hand, tends to be specific to ascertainment strategy, ethnicity, and cognitive test battery

Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis

The diterpenoid paclitaxel (Taxol) is a chemotherapy medication widely used as a first-line treatment against several types of solid cancers. The supply of paclitaxel from natural sources is limited. However, missing knowledge about the genes involved in several specific metabolic steps of paclitaxel biosynthesis has rendered it difficult to engineer the full pathway. In this study, we used a combination of transcriptomics, cell biology, metabolomics, and pathway reconstitution to identify the complete gene set required for the heterologous production of paclitaxel. We identified the missing steps from the current model of paclitaxel biosynthesis and confirmed the activity of most of the missing enzymes via heterologous expression in Nicotiana benthamiana. Notably, we identified a new C4β-C20 epoxidase that could overcome the first bottleneck of metabolic engineering. We used both previously characterized and newly identified oxomutases/epoxidases, taxane 1β-hydroxylase, taxane 9α-hydroxylase, taxane 9α-dioxygenase, and phenylalanine-CoA ligase, to successfully biosynthesize the key intermediate baccatin III and to convert baccatin III into paclitaxel in N. benthamiana. In combination, these approaches establish a metabolic route to taxoid biosynthesis and provide insights into the unique chemistry that plants use to generate complex bioactive metabolites

Anopheles gambiae: historical population decline associated with regional distribution of insecticide-treated bed nets in western Nyanza Province, Kenya

<p>Abstract</p> <p>Background</p> <p>High coverage of insecticide-treated bed nets in Asembo and low coverage in Seme, two adjacent communities in western Nyanza Province, Kenya; followed by expanded coverage of bed nets in Seme, as the Kenya national malaria programme rolled out; provided a natural experiment for quantification of changes in relative abundance of two primary malaria vectors in this holoendemic region. Both belong to the <it>Anopheles gambiae sensu lato (s.l.) </it>species complex, namely <it>A. gambiae sensu stricto (s.s.) </it>and <it>Anopheles arabiensis</it>. Historically, the former species was proportionately dominant in indoor resting collections of females.</p> <p>Methods</p> <p>Data of the relative abundance of adult <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>sampled from inside houses were obtained from the literature from 1970 to 2002 for sites west of Kisumu, Kenya, to the region of Asembo ca. 50 km from the city. A sampling transect was established from Asembo (where bed net use was high due to presence of a managed bed net distribution programme) eastward to Seme, where no bed net programme was in place. Adults of <it>A. gambiae s.l. </it>were sampled from inside houses along the transect from 2003 to 2009, as were larvae from nearby aquatic habitats, providing data over a nearly 40 year period of the relative abundance of the two species. Relative proportions of <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were determined for each stage by identifying species by the polymerase chain reaction method. Household bed net ownership was measured with surveys during mosquito collections. Data of blood host choice, parity rate, and infection rate for <it>Plasmodium falciparum </it>in <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were obtained for a sample from Asembo and Seme from 2005.</p> <p>Results</p> <p><it>Anopheles gambiae s.s. </it>adult females from indoor collections predominated from 1970 to 1998 (ca. 85%). Beginning in 1999, <it>A. gambiae </it>s.s decreased proportionately relative to <it>A. arabiensis</it>, then precipitously declined to rarity coincident with increased bed net ownership as national bed net distribution programmes commenced in 2004 and 2006. By 2009, <it>A. gambiae s.s. </it>comprised proportionately ca. 1% of indoor collections and <it>A. arabiensis </it>99%. In Seme compared to Asembo in 2003, proportionately more larvae were <it>A. gambiae s.s.</it>, larval density was higher, and more larval habitats were occupied. As bed net use rose in Seme, the proportion of <it>A. gambiae </it>larvae declined as well. These trends continued to 2009. Parity and malaria infection rates were lower in both species in Asembo (high bed net use) compared to Seme (low bed net use), but host choice did not vary within species in both communities (predominantly cattle for <it>A. arabiensis</it>, humans for <it>A. gambiae s.s.</it>).</p> <p>Conclusions</p> <p>A marked decline of the <it>A. gambiae s.s. </it>population occurred as household ownership of bed nets rose in a region of western Kenya over a 10 year period. The increased bed net coverage likely caused a mass effect on the composition of the <it>A. gambiae s.l. </it>species complex, resulting in the observed proportionate increase in <it>A. arabiensis </it>compared to its closely related sibling species, <it>A. gambiae s.s. </it>These observations are important in evaluating the process of regional malaria elimination, which requires sustained vector control as a primary intervention.</p

The relationship between perceived social support and depressive symptoms in informal caregivers of community-dwelling older persons in Chile

AIM: Depression among caregivers of older persons is a serious concern, but it is often overlooked and neglected in developing countries. The aim of this study was to examine the relationship between perceived social support and depression in informal caregivers of community-dwelling older persons in Chile. Methods: We analyzed cross-sectional secondary data on 377 dyads of community-dwelling older persons and their informal caregivers from a nationwide survey in Chile. The Duke-UNC Functional Social Support Questionnaire (FSSQ) was used to measure caregivers’ perceived social support, and the Center for Epidemiologic Studies Depression Scale assessed their depression. Results: In this study, 76.9% of the caregivers perceived a high level of social support, and 46.9% were assessed as having depression. Based on multivariable analysis, factors that decrease the likelihood of being depressed are a high level of social support (odds ratio (OR) = 0.311, 95% confidence interval (CI): 0.167–0.579) and having taken holidays in the past 12 months (OR = 0.513, 95%CI: 0.270–0.975). Factors that increase the likelihood of being depressed are being a female caregiver (OR = 2.296, 95%CI: 1.119–4.707), being uninsured (OR = 4.321, 95%CI: 1.750–10.672), being the partner or spouse of the care recipient (OR = 3.832, 95%CI: 1.546–9.493), and the number of hours of care (OR = 1.053, 95%CI: 1.021–1.085). Conclusion: Higher levels of perceived social support and holidays were associated with lower levels of depression. However, being female, being the care recipient's partner or spouse, being uninsured, and having long care periods had detrimental effects. Interventions to preserve and enhance perceived social support could help improve depressive symptoms in informal caregivers. Additionally, support should be available to caregivers who are women, uninsured, and the care recipient's partner or spouse, as well as those who provide care for long hours, to ensure they have respite from their caregiving role

The reliability and heritability of cortical folds and their genetic correlations across hemispheres

Cortical folds help drive the parcellation of the human cortex into functionally specific regions. Variations in the length, depth, width, and surface area of these sulcal landmarks have been associated with disease, and may be genetically mediated. Before estimating the heritability of sulcal variation, the extent to which these metrics can be reliably extracted from in-vivo MRI must be established. Using four independent test-retest datasets, we found high reliability across the brain (intraclass correlation interquartile range: 0.65–0.85). Heritability estimates were derived for three family-based cohorts using variance components analysis and pooled (total N \u3e 3000); the overall sulcal heritability pattern was correlated to that derived for a large population cohort (N \u3e 9000) calculated using genomic complex trait analysis. Overall, sulcal width was the most heritable metric, and earlier forming sulci showed higher heritability. The inter-hemispheric genetic correlations were high, yet select sulci showed incomplete pleiotropy, suggesting hemisphere-specific genetic influences