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Background: Antibody-mediated rejection (AMR) often progresses to poor health outcomes in lung transplant recipients (LTRs). This, combined with the relatively insensitive clinical tools used for its diagnosis (spirometry, histopathology) led us to determine whether clinical AMR is diagnosed significantly later than its pathologic onset. In this study, we leveraged the high sensitivity of donor-derived cell-free DNA (ddcfDNA), a novel genomic tool, to detect early graft injury after lung transplantation., Methods: We adjudicated AMR and acute cellular rejection (ACR) in 157 LTRs using the consensus criteria of the International Society for Heart and Lung Transplantation (ISHLT). We assessed the kinetics of allograft injury in relation to ACR or AMR using both clinical criteria (decline in spirometry from baseline) and molecular criteria (ddcfDNA); percent ddcfDNA was quantitated via shotgun sequencing. We used a mixed-linear model to assess the relationship between and ddcfDNA levels and donor-specific antibodies (DSA) in AMR + LTRs., Results: Compared with ACR, AMR episodes (n = 42) were associated with significantly greater allograft injury when assessed by both spirometric (0.1 liter vs -0.6 liter, p < 0.01) and molecular (ddcfDNA) analysis (1.1% vs 5.4%, p < 0.001). Allograft injury detected by ddcfDNA preceded clinical AMR diagnosis by a median of 2.8 months. Within the same interval, spirometry or histopathology did not reveal findings of allograft injury or dysfunction. Elevated levels of ddcfDNA before clinical diagnosis of AMR were associated with a concurrent rise in DSA levels., Conclusion: Diagnosis of clinical AMR in LTRs lags behind DSA-associated molecular allograft injury as assessed by ddcfDNA., (Copyright © 2018. Published by Elsevier Inc.)

New approaches to optimization of cancer drug development in the laboratory and the clinic will be required to fully achieve the goal of individualized, precision cancer therapy. Improved preclinical models that more closely reflect the now recognized genomic complexity of human cancers are needed. Here we describe a collaborative research project that integrates core resources of The Jackson Laboratory Basic Science Cancer Center with genomics and clinical research facilities at the UC Davis Comprehensive Cancer Center to establish a clinically and genomically annotated patient-derived xenograft (PDX) platform designed to enhance new drug development and strategies for targeted therapies. Advanced stage non-small-cell lung cancer (NSCLC) was selected for initial studies because of emergence of a number of "druggable" molecular targets, and recent recognition of substantial inter- and intrapatient tumor heterogeneity. Additionally, clonal evolution after targeted therapy interventions make this tumor type ideal for investigation of this platform. Using the immunodeficient NOD scid gamma mouse, > 200 NSCLC tumor biopsies have been xenotransplanted. During the annotation process, patient tumors and subsequent PDXs are compared at multiple levels, including histomorphology, clinically applicable molecular biomarkers, global gene expression patterns, gene copy number variations, and DNA/chromosomal alterations. NSCLC PDXs are grouped into panels of interest according to oncogene subtype and/or histologic subtype. Multiregimen drug testing, paired with next-generation sequencing before and after therapy and timed tumor pharmacodynamics enables determination of efficacy, signaling pathway alterations, and mechanisms of sensitivity-resistance in individual models. This approach should facilitate derivation of new therapeutic strategies and the transition to individualized therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The Bispectral Index (BIS) monitor has been suggested as a potential tool to measure depth of sedation in paediatric intensive care unit (PICU) patients. The primary aim of our observational study was to assess the difference in BIS values between the left and right sides of the brain. Secondary aims were to compare BIS and COMFORT score and to assess change in BIS with tracheal suctioning., Methods: Nineteen ventilated and sedated PICU patients had paediatric BIS sensors applied to either side of their forehead. Each patient underwent physiotherapy involving tracheal suctioning. Their BIS data and corresponding COMFORT score, assessment as by their respective nurses, were recorded before, during, and after physiotherapy., Results: Seven patients underwent more than one physiotherapy session; therefore, 28 sets of data were collected. The mean BIS difference values (and 95% CI) between left BIS and right BIS for pre-, during, and post-physiotherapy periods were 9.2 (5.9-12.5), 15.8 (11.9-19.7), and 7.5 (5.2-9.7), respectively. Correlation between mean BIS, left brain BIS, and right brain BIS to COMFORT score was highly significant (P<0.001 for all three) during the pre- and post-physiotherapy period, but less so during the stimulated physiotherapy period (P=0.044, P=0.014, and P=0.253, respectively)., Conclusions: A discrepancy between left and right brain BIS exists, especially when the patient is stimulated. COMFORT score and BIS correlate well between light and moderate sedation.

Demographic shifts and other social and economic forces as well as the increasing concerns about environmental determinants of disease and dysfunction have focused more attention on the disproportionate burden of environmental risk on blacks and other minorities. This article reviews these developments and identifies related challenges and opportunities confronting the medical community in the prevention of environmentally provoked disease among black Americans.

In the past 2 years, cities have reported skyrocketing rates of violence, crime, and abusive behavior including intrafamilial homicides. Of the 1838 homicide deaths last year among teenagers between the ages of 15 and 19, 71% involved the use of a firearm. Among black males in the same age group, 82% of the deaths were associated with guns. Since 1968, homicide has been among the leading causes of death for black teenagers. These and large volumes of other data clearly indicate that violence and abusive behavior is a compelling public health problem.

Blood gas analysis an various haematological measurements were studied prospectively in forty patients suffering from lower limb fractures. Hypoxaemia (arterial PO2 of less than 70 mmHg at sea level) was common with a mean value for all patients of 76 mmHg, despite O2 therapy, when indicated. None of the haematological findings was significant except that every patient with a white blood cell count of less than 7000 per mm3 was also hypoxaemic. Not all patients with hypoxaemia had a relative leucopaenia. A white blood count of less than 7000 per mm3 in the first 72 h following trauma may therefore be considered as an indication for oxygen therapy.

A practical approach for assessing patient education needs in the ambulatory care setting was developed, tested, and administered to 100 individuals with four non-acute clinical problems. The approach allowed collection, with a single instrument, of a range of information pertinent to the management of a wide mix of disorders. Knowledge about diagnosis, medications, nonmedicinal procedures, emergency situations, and prognosis was collected as well as self-estimation of knowledge and personal information needs.While the assessment can be conducted by a physician, nurse, mid-level practitioner, or health educator in approximately five minutes, it can also be conducted in approximately ten minutes by other appropriately trained personnel. The information gained is useful to clinicians, health educators, and administrators. This practical approach to the assessment of patient learning needs is considered to have applicability for numerous conditions and a variety of clinical settings. The condensed patient learning needs assessment tool is provided (Table 1).