S-Phenylmercapturic acid (
S-PMA), is a urinary metabolite of benzene, thought to be derived from the condensation product of benzene oxide with glutathione.
S-PMA may be determined by GC, HPLC (UV ...or fluorescence detection), GC–MS, LC–MS/MS or immunoassays. The limit of sensitivities of most of these techniques is 1
μg/l urine or below. It has been suggested that
S-PMA may have value as a biomarker for low level human exposure to benzene, in view of the facts that urinary excretion of
S-PMA has been found to be related to airborne benzene in occupationally exposed workers, and that only low background levels of
S-PMA have been found in control subjects.
We have evaluated the use of
S-PMA as a biomarker, using a commercially available analytical service, in a multicentre European study of populations exposed to varying levels of benzene, in Italy (Milan, Genoa) and in Bulgaria (Sofia). These were filling station attendants, urban policemen, bus drivers, petrochemical workers and referents (a total of 623 subjects).
S-PMA was measured at the end of the work shift by an immunoassay procedure. Urinary benzene (in Milan only) and the benzene metabolite
trans,trans-muconic acid (
t,t-MA) were measured before and after the work shift. Air-borne benzene was measured as a monitor of exposure. Urinary benzene was the most discriminatory biomarker and showed a relationship with airborne benzene at all levels of exposure studied (including groups exposed to <0.1
ppm benzene), whereas
t,t-MA and
S-PMA, as determined by immunoassay, were suitable only in the highest exposed workers (petrochemical industry, geometric mean 1765
μg/m
3 (0.55
ppm) benzene). All three biomarkers were positively correlated with smoking as measured by urinary cotinine).
Excessive time in bed has negative effects on both physical conditioning and functioning. There are no data or practice guidelines relevant to how nurses should manage the in-bed times of nursing ...home residents, although all nursing homes receive a bedfast prevalence quality indicator report generated from the Minimum Data Set.
To compare nursing homes that score in the upper and lower quartiles on the Minimum Data Set bedfast prevalence quality indicator for proportion of bedfast residents, activity and mobility nursing care, and amount of time all residents spend in bed, and to evaluate whether residents who spend more time in bed are different from those who spend less time in bed according to functional measures.
A cohort design used medical records, resident interviews, and direct observation data to compare 15 nursing homes (n = 451 residents) on the proportion of bedfast residents, the amount of time residents spent in bed, the frequency of activity, and the scores on six activity and mobility care process indicators.
Significant differences were found between upper (i.e., higher prevalence of bedfast residents) and lower quartile nursing homes in the proportion of time residents were observed in bed (43% vs. 34%, respectively; p =.007), and in the proportion of residents who spent more than 22 hours in bed per day (18% vs. 8%, respectively; p =.002). All nursing homes underestimated the number of bedfast residents. The residents of upper quartile homes showed more activity episodes and reported receiving more walking assistance than the residents of lower quartile homes.
Minimum Data Set bedfast quality indicator identified nursing homes in which residents spent more time in bed, but did not reflect differences in activity and mobility care. In fact, upper quartile homes provided more activity and mobility care than lower quartile homes. Across all the nursing homes, most of the residents spent at least 17 hours a day in bed. Further study of activity and mobility care and bedfast outcomes in nursing homes is needed, and nurses need to note the amount of time nursing home residents spend in bed.
Given the inherent limitations of grades, many writing instructors probably have some difficulty choosing one letter or number that accurately captures and communicates a composition's many strengths ...and weaknesses. Given the existing plethora of disciplinary, institutional, and national guidelines for what should be taught and learned in the ubiquitous Freshman English or Freshman Composition course, those teaching this high-stakes course at community colleges often face even more challenges in applying normative and prescriptive guidelines to authentic and specific classroom situations and students. Eventually, sooner rather than later to survive the heavy paper load, each instructor constructs his or her individual cognitive grading schema to navigate among the many rocks and hard places. This qualitative, collective case study describes the textual and extra-textual elements and criteria six instructors considered when grading two English 100 (Freshman English) research papers; these six instructors, as well as three others who participated in this study's Phase I, were teaching at three community colleges in the University of Hawaii system. As the six participants proceeded from explaining their stated grading criteria to grading a paper written by an unknown student and finally to grading a paper written by one of their own students in Phase II, their grading processes often became more complex and less coherent in their attempts to weigh and integrate the written product, the writing process, and the individual student's progress.
To address the unmet medical need for an effective prophylactic vaccine against Ebola virus we assessed the safety and immunogenicity of three different two-dose heterologous vaccination regimens ...with a replication-deficient adenovirus type 26 vector-based vaccine (Ad26.ZEBOV), expressing Zaire Ebola virus glycoprotein, and a non-replicating, recombinant, modified vaccinia Ankara (MVA) vector-based vaccine, encoding glycoproteins from Zaire Ebola virus, Sudan virus, and Marburg virus, and nucleoprotein from the Tai Forest virus.
This randomised, observer-blind, placebo-controlled, phase 2 trial was done at seven hospitals in France and two research centres in the UK. Healthy adults (aged 18–65 years) with no history of Ebola vaccination were enrolled into four cohorts. Participants in cohorts I–III were randomly assigned (1:1:1) using computer-generated randomisation codes into three parallel groups (randomisation for cohorts II and III was stratified by country and age), in which participants were to receive an intramuscular injection of Ad26.ZEBOV on day 1, followed by intramuscular injection of MVA-BN-Filo at either 28 days (28-day interval group), 56 days (56-day interval group), or 84 days (84-day interval group) after the first vaccine. Within these three groups, participants in cohort II (14:1) and cohort III (10:3) were further randomly assigned to receive either Ad26.ZEBOV or placebo on day 1, followed by either MVA-BN-Filo or placebo on days 28, 56, or 84. Participants in cohort IV were randomly assigned (5:1) to receive one dose of either Ad26.ZEBOV or placebo on day 1 for vector shedding assessments. For cohorts II and III, study site personnel, sponsor personnel, and participants were masked to vaccine allocation until all participants in these cohorts had completed the post-MVA-BN-Filo vaccination visit at 6 months or had discontinued the trial, whereas cohort I was open-label. For cohort IV, study site personnel and participants were masked to vaccine allocation until all participants in this cohort had completed the post-vaccination visit at 28 days or had discontinued the trial. The primary outcome, analysed in all participants who had received at least one dose of vaccine or placebo (full analysis set), was the safety and tolerability of the three vaccination regimens, as assessed by participant-reported solicited local and systemic adverse events within 7 days of receiving both vaccines, unsolicited adverse events within 42 days of receiving the MVA-BN-Filo vaccine, and serious adverse events over 365 days of follow-up. The secondary outcome was humoral immunogenicity, as measured by the concentration of Ebola virus glycoprotein-binding antibodies at 21 days after receiving the MVA-BN-Filo vaccine. The secondary outcome was assessed in the per-protocol analysis set. This study is registered at ClinicalTrials.gov, NCT02416453, and EudraCT, 2015-000596-27.
Between June 23, 2015, and April 27, 2016, 423 participants were enrolled: 408 in cohorts I–III were randomly assigned to the 28-day interval group (123 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), the 56-day interval group (124 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), and the 84-day interval group (117 to receive Ad26.ZEBOV and MVA-BN-Filo, and 18 to receive placebo), and 15 participants in cohort IV were assigned to receive Ad26.ZEBOV and MVA-BN-Filo (n=13) or to receive placebo (n=2). 421 (99·5%) participants received at least one dose of vaccine or placebo. The trial was temporarily suspended after two serious neurological adverse events were reported, one of which was considered as possibly related to vaccination, and per-protocol vaccination was disrupted for some participants. Vaccinations were generally well tolerated. Mild or moderate local adverse events (mostly pain) were reported after 206 (62%) of 332 Ad26.ZEBOV vaccinations, 136 (58%) of 236 MVA-BN-Filo vaccinations, and 11 (15%) of 72 placebo injections. Systemic adverse events were reported after 255 (77%) Ad26.ZEBOV vaccinations, 116 (49%) MVA-BN-Filo vaccinations, and 33 (46%) placebo injections, and included mostly mild or moderate fatigue, headache, or myalgia. Unsolicited adverse events occurred after 115 (35%) of 332 Ad26.ZEBOV vaccinations, 81 (34%) of 236 MVA-BN-Filo vaccinations, and 24 (33%) of 72 placebo injections. At 21 days after receiving the MVA-BN-Filo vaccine, geometric mean concentrations of Ebola virus glycoprotein-binding antibodies were 4627 ELISA units (EU)/mL (95% CI 3649–5867) in the 28-day interval group, 10 131 EU/mL (8554–11 999) in the 56-day interval group, and 11 312 mL (9072–14106) in the 84-day interval group, with antibody concentrations persisting at 1149–1205 EU/mL up to day 365.
The two-dose heterologous regimen with Ad26.ZEBOV and MVA-BN-Filo was safe, well tolerated, and immunogenic, with humoral and cellular immune responses persisting for 1 year after vaccination. Taken together, these data support the intended prophylactic indication for the vaccine regimen.
Innovative Medicines Initiative and Janssen Vaccines & Prevention BV.
For the French translation of the abstract see Supplementary Materials section.
We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the ...number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.
To assess the efficacy and safety of closed-loop control (CLC) insulin delivery system in adolescents and young adults with type 1 diabetes.
Prespecified subanalysis of outcomes in adolescents and ...young adults aged 14-24 years old with type 1 diabetes in a previously published 6-month multicenter randomized trial. Participants were randomly assigned 2:1 to CLC (Tandem Control-IQ) or sensor augmented pump (SAP, various pumps+Dexcom G6 CGM) and followed for 6 months.
Mean age of the 63 participants was 17 years, median type 1 diabetes duration was 7 years, and mean baseline HbA1c was 8.1%. All 63 completed the trial. Time in range (TIR) increased by 13% with CLC versus decreasing by 1% with SAP (adjusted treatment group difference = +13% +3.1 h/day; 95% confidence interval CI 9-16,
< 0.001), which largely reflected a reduction in time >180 mg/dL (adjusted difference -12% -2.9 h/day,
< 0.001). Time <70 mg/dL decreased by 1.6% with CLC versus 0.3% with SAP (adjusted difference -0.7% -10 min/day, 95% CI -1.0% to -0.2%,
= 0.002). CLC use averaged 89% of the time for 6 months. The mean adjusted difference in HbA1c after 6 months was 0.30% in CLC versus SAP (95% CI -0.67 to +0.08,
= 0.13). There was one diabetic ketoacidosis episode in the CLC group.
CLC use for 6 months was substantial and associated with improved TIR and reduced hypoglycemia in adolescents and young adults with type 1 diabetes. Thus, CLC has the potential to improve glycemic outcomes in this challenging age group. The clinical trial was registered with ClinicalTrials.gov (NCT03563313).
Objective
To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood‐onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant ...improvement (CRIcSLE).
Methods
Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRIcSLE and rate a total of 433 unique patient profiles for the presence/absence of CRIcSLE. Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well‐being (patient‐global), physician assessment of cSLE activity (MD‐global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein‐to‐creatinine ratio, and Child Health Questionnaire physical summary score. Percentage and absolute changes in these cSLE‐CRVs (baseline versus follow‐up) were considered in order to develop candidate algorithms and validate their performance (sensitivity, specificity, area under the receiver operating characteristic curve AUC; range 0–1).
Results
During an international consensus conference, unanimous agreement on a definition of CRIcSLE was achieved; cSLE experts (n = 13) concurred (100%) that the preferred CHILI algorithm considers absolute changes in the cSLE‐CRVs. After transformation to a range of 0–100, a CHILI score of ≥54 had outstanding accuracy for identifying CRIcSLE (AUC 0.93, sensitivity 81.1%, and specificity 84.2%). CHILI scores also reflect minor, moderate, and major improvement for values exceeding 15, 68, and 92, respectively (all AUC ≥0.92, sensitivity ≥93.1%, and specificity ≥73.4%).
Conclusion
The CHILI is a new, seemingly highly accurate index for measuring CRI in cSLE over time. This index is useful to categorize the degree of response to therapy in children and adolescents with cSLE.
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