TheMycobacterium tuberculosiscomplex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity inM. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of theM. tuberculosis-specific IS6110insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110elements as the most likely mechanism of the deletion events. IS6110insertion into hot-spots within the genome ofM. tuberculosisprovides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.

Increased large artery stiffness occurs in a range of inflammatory conditions indicating an ageing of the vasculature and additionally being an independent risk factor for cardiovascular events. We determined large artery parameters in adults with cystic fibrosis (CF).50 clinically stable adult patients with CF (mean¡SD age 28.0¡8.2 yrs) and 26 controls matched for age, sex and body mass index were studied. Central aortic blood pressure, augmentation index (AIx) and aortic pulse wave velocity (PWV) were determined using applanation tonometry. Lung function, diabetic status and C-reactive protein (CRP) were also determined.Mean¡SD AIx was greater in patients than controls, 8.5¡11.1% and -1.8¡13.1%, respectively (p,0.001), while PWV was similar. Although AIx was greatest in the sub-group with CF-related diabetes (CFRD), it was also increased in the non-CFRD sub-group when compared with controls. In patients, AIx was related to log 10 CRP (r50.33) and forced vital capacity (r5 -0.34; both p,0.05), and CRP remained predictive in multiple regression.AIx is increased in adults with CF, in the presence of a normal blood pressure and independent of diabetic status. AIx was related to the systemic inflammatory status. These findings have implications for management and require further exploration so that cardiovascular health can be maintained.

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Objective: We examined efforts by a Mississippi court to base pretrial release decisions on risk assessment rather than primarily on bond. Hypotheses: (a) Pretrial detention will be shorter than that associated with prevailing bond practices in the same counties. (b) Rearrest rates will be lower than a similar pretrial population in a nearby southern state. (c) False positive rates for predicting rearrests will be higher for African American than Caucasian participants. (d) Pretrial detention will be longer for African American participants because of higher risk scores or assessment overrides. Method: Pretrial defendants (N = 521) completed the Risk and Needs Triage (RANT) within 2 weeks of arrest, and outcomes examined included the length of pretrial detention, index case dispositions, and rearrest rates. Results: (a) Pretrial detention averaged approximately 60 days compared with prevailing detentions averaging approximately 90 and 180 days in the same counties. (b) Pretrial rearrest rates were 17 percentage points higher than a similar pretrial population; however, representative comparison data are unavailable to confidently measure recidivism impacts. (c) Positive predictive power did not differ by race in predicting pretrial rearrests, SE = .04, 95% CI [.11, −.06], z = .61, p = .54, d = .08. (d) Despite comparable risk scores, African American participants were detained significantly longer than Caucasian participants (M = 60.92 vs. 45.58 days), p = .038, d = .18, 95% CI [.01, .36], and were less likely to receive a diversion opportunity (11% vs. 23%), p = .009, V = .17. Conclusion: The observational design precludes causal conclusions; however, risk assessment was associated with shorter pretrial detention than prevailing bond practices with no racial disparities in risk prediction. Greater attention to risk assessment may reduce racial inequities in pretrial conditions. Representative comparison data are needed to measure the recidivism impacts of pretrial reform initiatives.

In this retrospective observational study performed in a high-volume hepatobiliary-pancreatic unit, we evaluated the effect of a surgery-specific goal-directed therapy (GDT) physiologic algorithm on complications and length of hospital stay. We compared patients who underwent pancreaticoduodenectomy with either a standardised Enhanced Recovery After Surgery program (usual care group), or a standardised Enhanced Recovery After Surgery program in combination with a surgeryspecific cardiac output-guided algorithm (GDT group). We included 145 consecutive patients: 47 in the GDT group and 98 in the usual care group. Multivariable associations between GDT and lengths of stay and complications were investigated using negative binomial regression. Postoperative complications were common and occurred at similar frequencies amongst the GDT and usual care groups: 64% versus 68% respectively, P=0.71; odds ratio 0.82; (95% confidence interval 0.39-1.70). There were fewer cardiorespiratory complications in the GDT group. Median (interquartile range) length of hospital stay was ten days (8.0-14.0) in the GDT group compared to 13 days (8.8-21.3) in the usual care group, P=0.01. Median (interquartile range) total intraoperative fluid was 3,000 ml (2,050-4,175) in the GDT group compared to 4,500 ml (3,275-5,325) in the usual care group, P <0.0001; but by day one, the median (interquartile range) fluid balance was similar (1,198 ml [700-1,729] in the GDT group versus 977 ml [419-2,044] in the usual care group, P=0.96). Use of vasoactive medications was higher in the GDT group. In our patients undergoing pancreaticoduodenectomy, GDT was associated with restrictive intraoperative fluid intervention, fewer cardiorespiratory complications and a shorter hospital length of stay compared to usual care. However, we could not exclude an influence of surgical caseload, which we have previously found to be an important variable. We also could not relate the increased hospital length of stay to cardiorespiratory complications in individual patients. Therefore, these observational retrospective findings would require confirmation in a prospective randomised study.