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Sepsis is a major cause of mortality among hospitalized patients worldwide. Shorter time to administration of broad-spectrum antibiotics is associated with improved outcomes, but early recognition of sepsis remains a major challenge. In a two-center cohort study with prospective sample collection from 1400 adult patients in emergency departments suspected of sepsis, we sought to determine the diagnostic and prognostic capabilities of a machine-learning algorithm based on clinical data and a set of uncommonly measured biomarkers. Specifically, we demonstrate that a machine-learning model developed using this dataset outputs a score with not only diagnostic capability but also prognostic power with respect to hospital length of stay (LOS), 30-day mortality, and 3-day inpatient re-admission both in our entire testing cohort and various subpopulations. The area under the receiver operating curve (AUROC) for diagnosis of sepsis was 0.83. Predicted risk scores for patients with septic shock were higher compared with patients with sepsis but without shock (p < 0.0001). Scores for patients with infection and organ dysfunction were higher compared with those without either condition (p < 0.0001). Stratification based on predicted scores of the patients into low, medium, and high-risk groups showed significant differences in LOS (p < 0.0001), 30-day mortality (p < 0.0001), and 30-day inpatient readmission (p < 0.0001). In conclusion, a machine-learning algorithm based on electronic medical record (EMR) data and three nonroutinely measured biomarkers demonstrated good diagnostic and prognostic capability at the time of initial blood culture., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Due to their dynamic, stimuli-responsive nature, non-covalent interactions represent versatile design elements that can be found in nature in many molecular processes or materials, where adaptive behavior or reversible connectivity is required. Examples include molecular recognition processes, which trigger biological responses or cell-adhesion to surfaces, and a broad range of animal secreted adhesives with environment-dependent properties. Such advanced functionalities have inspired researchers to employ similar design approaches for the development of synthetic polymers with stimuli-responsive properties. The utilization of non-covalent interactions for the design of adhesives with advanced functionalities such as stimuli responsiveness, bonding and debonding on demand capability, surface selectivity or recyclability is a rapidly emerging subset of this field, which is summarized in this review.

Hydrogen-bonded, side-chain-functionalized supramolecular poly(alkyl methacrylate)s were investigated as light- and temperature-responsive reversible adhesives that are useful for bonding and debonding on demand applications. Here, 2-hydroxyethyl methacrylate (HEMA) was functionalized with 2-ureido-4[1H]pyrimidinone (UPy) via a hexamethylenediisocyanate (HMDI) linker, to create a monomer (UPy-HMDI-HEMA) that serves to form supramolecular cross-links by way of forming quadruple hydrogen bonded dimers. UPy-HMDI-HEMA was copolymerized with either hexyl methacrylate or butyl methacrylate to create copolymers comprising 2.5, 5, or 10 mol % of the cross-linker. The mechanical properties of all (co)polymers were investigated with stress-strain experiments and dynamic mechanical analysis. Furthermore, the adhesive properties were studied at temperatures between 20 and 60 °C by testing single lap joints formed with stainless steel substrates. It was found that increasing the concentration of the UPy-HMDI-HEMA cross-linker leads to improved mechanical and adhesive properties at elevated temperatures. Concurrently, the reversibility of the bond formation remained unaffected, where rebonded samples displayed the same adhesive strength as regularly bonded samples. Debonding on demand abilities were also tested exemplarily for one copolymer, which for light-induced debonding experiments was blended with a UV-absorber that served as light-heat converter. Single lap joints were subjected to a constant force and heated or irradiated with UV light until debonding occurred. The necessary debonding temperature was comparable for direct heating and UV irradiation and varied between 28 and 82 °C, depending on the applied force. The latter also influenced the debonding time, which under the chosen conditions ranged from 30 s to 12 min.

Light-responsive supramolecular polymers were applied as reversible adhesives that permit bonding and debonding on demand features. A telechelic poly(ethylene-co-butylene) (PEB) was functionalized with either self-complementary hydrogen-bonding ureidopyrimidinone (UPy) motifs (UPy-PEB-UPy) or 2,6-bis(1'-methylbenzimidazolyl)-pyridine (Mebip) ligands (Mebip-PEB-Mebip), which can coordinate to metal ions (Zn(NTf2)2) and form a metallosupramolecular polymer with the sum formula [Znx(Mebip-PEB-Mebip)](NTf2)2x, with x ≈ 1. In the latter case, light-heat conversion is facilitated by the ultraviolet (UV) light-absorbing metal-ligand motifs, while in the case of UPy-PEB-UPy a UV absorber was added for this purpose. Single lap joints were prepared by sandwiching films of the supramolecular polymers of a thickness of 80-100 μm between two glass, quartz, or stainless steel substrates and bonded by exposure to either UV light (320-390 nm, 900 mW/cm(2)) or heat (80 or 200 °C for UPy-PEB-UPy and the metallopolymer, respectively). UPy-PEB-UPy and [Zn0.8Mebip-PEB-Mebip](NTf2)1.6 displayed a shear strength of 0.9-1.2 and 1.8-2.5 MPa, respectively. When lap joints were placed under load and exposed to light or heat, the samples debonded within seconds. They could be rebonded through exposure to light or heat, and the original adhesive properties were recovered.

Objective: To assess the relationship between hospital patients' quality of care ratings and their experiences with health-related information exchanges and communication during hospitalization., Design: Cross-sectional multivariate dimensional analysis of data from a quality of care experience questionnaire of hospital patients comparing scores across three levels of reported satisfaction., Setting and Participants: Five thousand nine hundred and fifty-two patients from a Swiss University Hospital responded to the questionnaire at discharge during 2010., Main Outcome Measures: Survey questions measuring patients' evaluation of quality of care, patient loyalty and overall satisfaction., Results: Different levels of reported satisfaction are associated with differing experiences of health-related information and communication during a hospital stay., Conclusions: Patients who report lower satisfaction appear to attribute to the hospital staff enduring negative dispositions from behaviours that may be due to specific situational contexts. Negative experiences appear to influence scores on most other communication and information domains. Patients who report higher satisfaction, in contrast, appear to differentiate negative experiences and positive experiences and they appear to relativize and compartmentalize negative experiences associated with their hospital stay.

Purpose: To map the gene for autosomal dominant cataracts (ADC) in an American white family of European descent., Methods: Ophthalmic examinations and linkage analyses using a variety of polymorphisms were performed; two-point lod scores calculated., Results: Affected individuals (14 studied) exhibited variable expressivity of embryonal nuclear opacities based on morphology, location within the lens, and density. This ADC locus to 12q13 was mapped on the basis of statistically significantly positive lod scores and no recombinations (theta(m) = theta(f) = 0) with markers D12S368, D12S270, D12S96, D12S359, D12S1586, D12S312, D12S1632, D12S90, and D12S83; assuming full penetrance, a maximum lod score of 4.73 was calculated between the disease locus and D12S90., Conclusions: The disease in this family represents the first ADC locus on chromosome 12; major intrinsic protein of lens fiber (MIP) is a candidate gene.

Purpose: Gap junctions play a critical role in the metabolic homeostasis and maintenance of transparency of fibers within the ocular lens. As part of a long-term effort to establish the relationship between lens gap junction proteins, normal lens development, and cataractogenesis, we report here the regional localization of the human MP70 (Connexin 50) gene., Methods: Fluorescence in situ hybridization (FISH) was used to regionally map the human MP70 gene. The DNA probe contained the entire MP70 coding region within a clone isolated from a human genomic DNA library., Results: The human gene encoding the lens intrinsic membrane protein MP70 was regionally mapped to q21.1 on the long arm of chromosome 1., Conclusions: This study confirms the previous provisional assignment of MP70 to human chromosome 1 and regionally localizes the gene to 1q21.1. When combined with previous mapping information, these data are consistent with the hypothesis that a genetic lesion in the gene encoding the lens intrinsic membrane protein MP70 may be the underlying molecular defect for zonular pulverulent (Coppock) cataract. Furthermore, these combined data support the hypothesis that other forms of human hereditary cataract may be the result of a mutation in one or more of the genes encoding gap junction proteins found in the ocular lens.

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families.

The prevalence of TaqI A alleles of the D2 dopamine receptor (DRD2) gene was examined in two subgroups of medically ill nonalcoholics (more prevalent and less prevalent substance users, MPSU and LPSU, respectively) and in two subgroups of medically ill alcoholics (more severe and less severe alcoholics, MSA and LSA, respectively). The prevalence of the A1 allele in the 80 nonalcoholic and 73 alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009). In the four subgroups of these patients, the prevalence of this allele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA = 58.3%. Linear trend analysis showed that as the use of substances and severity of alcoholism increase, so does A1 prevalence (P = 0.001). Specific, subgroup comparisons showed A1 prevalence in MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04) higher than in LPSU and MPSU subgroups, respectively. Similarly, in a combined analysis of independent studies, A1 prevalence in MSA was higher when compared to LSA (P < 5 x 10(-3), MPSU (P < 10(-4) and LPSU (P < 10(-8) subgroups. There was virtually no difference in the prevalence of the A1 allele between LSA and MPSU subgroups. None of the specific medical or neuropsychiatric complications of alcoholism was associated with the A1 allele. In conclusion, the severity of alcohol dependence in alcoholics and of substance use behaviors in controls are important variables in DRD2 allelic association. The present report and converging lines of evidence suggest that the DRD2 locus could represent a prominent gene risk factor for susceptibility to severe alcoholism. However, other genes and environmental factors, when combined, still play the larger role.

Goosecoid is a homeobox gene first isolated from a Xenopus dorsal lip cDNA library. Homologous genes have been isolated from mouse, zebrafish, and chick. In all species examined, the gene is expressed and plays an important role during the process of gastrulation in early embryonic development. We report here the cloning of the human goosecoid gene (GSC) from a genomic library and the sequence of its encoded protein. The genomic organization and protein sequence of the human gene are highly conserved with respect to those of its Xenopus and mouse counterparts: all three genes consist of three exons, with conserved exon-intron boundaries; the sequence of the homeodomain is 100% conserved in most vertebrates. Using somatic cell hybrid and chromosomal in situ hybridization, the gene was mapped to chromosome 14q32.1.

The physiologic and behavioral effects of pharmacologic agents that interfere with the transport of monoamine neurotransmitters into vesicles suggest that vesicular amine transport may contribute to human neuropsychiatric disease. To determine whether an alteration in the genes that encode vesicular amine transport contributes to the inherited component of these disorders, we have isolated a human cDNA for the brain transporter and localized the human vesicular amine transporter genes. The human brain synaptic vesicle amine transporter (SVAT) shows unexpected conservation with rat SVAT in the regions that diverge extensively between rat SVAT and the rat adrenal chromaffin granule amine transporter (CGAT). Using the cloned sequences with a panel of mouse-human hybrids and in situ hybridization for regional localization, the adrenal CGAT gene (or VAT1) maps to human chromosome 8p21.3 and the brain SVAT gene (or VAT2) maps to chromosome 10q25. Both of these sites occur very close to if not within previously described deletions that produce severe but viable phenotypes.

Phosducin is a soluble photoreceptor phosphoprotein that probably modulates phototransduction in the retina and thus qualifies as a potential candidate gene for retinitis pigmentosa. Using both human/mouse somatic cell hybrids and in situ hybridization to human metaphase chromosomes, we have mapped this gene to chromosome 1q25-1q32.1.