The effectiveness of diversion programmes for offenders using Class A drugs: a systematic review and meta-analysis

Aims: To review existing evidence on effectiveness of community-based diversion programmes for Class A drug-using offenders.

Methods: 31 databases were searched for studies published 1985–2012 (update search 2012–2016) involving community-based Criminal Justice System diversion of Class A drug users via voluntary or court-mandated treatment.

Findings: 16 studies were initially included (US, 10; UK, 4; Canada, 1; Australia, 1). There was evidence for a small impact of diversion to treatment on drug use reduction (primary Class A drug use: OR 1.68, CI 1.12–2.53; other drug use: OR 2.60, 1.70–3.98). Class A drug users were less likely to complete treatment (OR 0.90, 0.87–0.94) than users of other drugs. There was uncertainty surrounding results for offending, which were not pooled due to lack of outcome measure comparability and heterogeneity. Individual studies pointed to a minor effect of diversion on offending. Findings remained unchanged following an update review (evidence up to March 2016: US, 3; Australia, 1).

Conclusions: Treatment accessed via community-based diversion is effective at reducing drug use in Class A drug-using offenders. Evidence of a reduction in offending amongst this group as a result of diversion is uncertain. Poor methodological quality and data largely limited to US methamphetamine users limits available evidence.     

Risk-adjusted comparisons of bloodstream infection rates in neonatal intensive-care units

Comparisons of bloodstream infection (BSI) rates between neonatal intensive-care units (NICUs) should take into account differences in babies' vulnerability and invasive procedures that can introduce infection. Our aim was to investigate which risk factors recorded in routine records should be adjusted for when NICUs are compared. This was a retrospective cohort study using routine records for two London NICUs. We analysed rates of BSI with Poisson regression models. The level of neonatal care used by the National Health Service was the strongest predictor of BSI incidence. The rate ratios for BSI, adjusted for birthweight, inborn/outborn status, and postnatal age, were 3.15 (95% CI 2.01–4.94) for intensive care and 6.58 (95% CI 4.18-10.36) for high-dependency care, relative to special care. Total parenteral nutrition was significantly associated with BSI incidence, but explained less of the variance among babies than level of care. A case—control study with the same dataset gave similar results. Further multicentre studies are required to confirm our predictive model. Until then, we recommend that comparisons of BSI rates between NICUs should include adjustments for level of care, birthweight, inborn/outborn status, and postnatal age, with the use of routinely recorded standardized measures in hospital administrative data.     

Endothelial lipase promotes the catabolism of ApoB-containing lipoproteins

Endothelial lipase (EL) has been found to be a key enzyme in high-density lipoprotein (HDL) metabolism in mice, leading to the concept that inhibition of EL could be a novel strategy for raising HDL cholesterol levels. However, mice are "HDL animals" and the effect of EL on atherogenic apoB-containing lipoproteins has not been elucidated. We previously found that EL is capable of hydrolyzing very low-density lipoprotein (VLDL) and LDL lipids ex vivo. To investigate the role of EL in the metabolism of apoB-containing lipoproteins in vivo, we expressed human EL in three mouse models of elevated apoB-containing lipoproteins: apoE-deficient, LDL receptor-deficient, and human apoB transgenic mice. Unexpectedly, hepatic expression of EL resulted in markedly decreased levels of VLDL/LDL cholesterol, phospholipid, and apoB accompanied by significantly increased LDL apolipoprotein and phospholipid catabolism. To determine whether lipolytic activity is required for this effect, we also expressed a catalytically inactive form of human EL (ELS149A); unexpectedly, expression of ELS149A did not lower and in fact increased plasma lipids. Coexpression and coimmunoprecipitation studies suggested that catalytically inactive ELS149A inhibits endogenous mouse EL, accounting for the increased lipid levels. We conclude that (1) in addition to its known effects on HDL metabolism, EL influences the metabolism of apoB-containing particles; (2) catalytic activity of EL is required for its effects on apoB-containing lipoproteins; and (3) overexpressed catalytically inactive EL inhibits endogenous mouse EL, resulting in increased levels of plasma lipids. In light of these results, inhibition of EL has the potential to raise levels of atherogenic lipoproteins in addition to HDL-C levels.     

Collection of peripheral blood stem cells in newly diagnosed myeloma patients without any prior cytoreductive therapy: the first step towards an 'operational cure'?

We have shown that primary therapy with non-myeloablative (140 mg/m(2)) high-dose melphalan (HDM) without hematopoietic support results in high response rates in untreated myeloma and very long-term survival of some patients. This study was designed to see if sufficient CD34 (+) cells can be harvested at presentation in newly diagnosed patients to administer myeloablative HDM (200 mg/m(2); HDM200) with autograft as primary therapy. This may improve outcome by rapid achievement of complete remission (CR) and possible avoidance of late myelodysplasia as a consequence of non-transplant induction chemotherapy. Thirty untreated patients received 1 g/m(2) methylprednisolone daily (days 1-6) and 12-16 micro g/kg G-CSF daily (days 3-6), and underwent leukapheresis on days 6 and 7. The median CD34(+) cell yield was 1.31 x10(6)/kg (range, 0.23-5.63), and was > or =1 x10(6)/kg in 73%. Cell yields were significantly lower than in 82 historical controls apheresed after completion of induction chemotherapy (median 2.16 x 10(6)/kg), and improved in patients who were apheresed again after induction chemotherapy. Three patients received primary therapy with HDM200 and autograft using these cells and attained CR. We conclude that it is possible to harvest stem cells in three-quarters of untreated myeloma patients. Increasing the number of apheresis procedures is needed to improve the number of CD34(+) cells collected.     

Harnessing Biomaterials to Engineer the Lymph Node Microenvironment for Immunity or Tolerance

Nanoparticles, microparticles, and other biomaterials are advantageous in vaccination because these materials provide opportunities to modulate specific characteristics of immune responses. This idea of “tuning” immune responses has recently been used to combat infectious diseases and cancer, and to induce tolerance during organ transplants or autoimmune disease. Lymph nodes and other secondary lymphoid organs such as the spleen play crucial roles in determining if and how these responses develop following vaccination or immunotherapy. Thus, by manipulating the local microenvironments within these immunological command centers, the nature of systemic immune response can be controlled. This review provides recent examples that harness the interactions between biomaterials and lymph nodes or other secondary lymphoid organs to generate immunity or promote tolerance. These strategies draw on mechanical properties, surface chemistry, stability, and targeting to alter the interactions of cells, signals, and vaccine components in lymph nodes. While there are still many unanswered questions surrounding how best to design biomaterial-based vaccines to promote specific structures or functions in lymph nodes, features such as controlled release and targeting will help pave the way for the next generation of vaccines and immunotherapies that generate immune responses tuned for specific applications.KEY WORDS: autoimmunity and tolerance, biomaterials, immunology, nanoparticles and microparticles, vaccine     

p55CDC25 is a nuclear protein required for the initiation of mitosis in human cells.

The cdc25+ gene of fission yeast encodes a phosphotyrosine phosphatase that dephosphorylates tyrosine-15 of p34cdc2 and thereby activates p34cdc2/cyclin to bring about entry into M phase. We have recently cloned a human homolog, CDC25, which rescues the M-phase initiation defect of yeast cdc25 temperature-sensitive mutants. Antibodies raised against the CDC25 gene product specifically recognize human proteins of approximately 55 and approximately 52 kDa. Microinjection of affinity-purified anti-CDC25 antibodies into HeLa cells inhibits entry into mitosis. These observations suggest that the CDC25 gene products are essential for the initiation of mitosis in human cells, similar to their homologs in fission yeast and Drosophila. CDC25 gene products, like p34CDC2, are localized primarily in the nucleus during interphase, suggesting that activation of p34CDC2/cyclin by p52/p55CDC25 occurs within the nucleus.     

Catalytic degradation of Orange II in aqueous solution using diatomite-supported bimetallic Fe/Ni nanoparticles

A functional diatomite-supported Fe/Ni nanocomposite successfully remediated Orange II contaminant in aqueous solution. The hypothesis was that diatomite-supported Fe/Ni would not only be more effective than Fe/Ni but also require less metallic loading to effect the catalytic reaction. Batch experiments indicate that 99.00% of Orange II was removed using diatomite-supported Fe/Ni, while only 86.64 and 3.59% of Orange II were removed using bimetallic Fe/Ni nanoparticles and diatomite, after 6 h of reaction, respectively. Characterisation by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) indicates that the use of diatomite as a support material reduced the aggregation of bimetallic Fe/Ni nanoparticles, thereby resulting in an enhancement in the reactivity. A synergistic mechanism for the removal of Orange II by diatomite-supported Fe/Ni was proposed which involves adsorption, followed by catalytic reduction. This study has demonstrated that diatomite may be a suitable support material for stabilizing and dispersing bimetallic Fe/Ni nanoparticles and the resulting diatomite-supported Fe/Ni composite could be a promising catalyst for the remediation of dye-contaminated wastewater.

A functional diatomite-supported Fe/Ni nanocomposite successfully remediated Orange II contaminant in aqueous solution.     

Pilot Randomized Controlled Trial of Motivational Interviewing with Sexual Minority Male Couples to Reduce Drug Use and Sexual Risk: The Couples Health Project

AIDS and Behavior - A randomized controlled trial evaluated the preliminary efficacy of a dyadically-delivered motivational interviewing (MI) intervention to reduce drug use and sexual risk in a...     

Luteinizing hormone release from chicken pituitary cells: synergism between calcium and protein kinase C and its inhibition by calmodulin antagonists

Continuous stimulation of cultured chicken pituitary cells with a native chicken hypothalamic GnRH, Gln8-GnRH, caused LH release, followed by rapid desensitization. Continuous exposure to calcium ionophore A23187 also produced a short-lived LH response, followed by desensitization. In contrast, continuous stimulation with a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), caused prolonged release of LH, reaching maximum amplitude after 1 h and slowly decreasing thereafter. Cells desensitized to GnRH remained fully responsive to A23187 and TPA, indicating that GnRH-mediated desensitization occurs at a level before protein kinase C activation and calcium mobilization. Simultaneous addition of A23187 and TPA resulted in a synergistic response which was independent of the order of addition of the two compounds. Synergism was also demonstrated between depolarizing concentrations of potassium and TPA and between veratridine and TPA, indicating that calcium entering via voltage-dependent channels also synergizes with phorbol ester. Despite the prolonged action of TPA, rapid pulsatile changes in LH release could be induced in cells treated with TPA and veratridine by rapidly changing the extracellular calcium concentration. This suggest that protein kinase C could function as an amplifier of the calcium signal generated by GnRH. Synergism between calcium and TPA was blocked by trifluoperazine, chlorpromazine, and W-7 [N-(6-aminohexyl)5-chloro-1-napthalenesulfonamide] at concentrations that had no effect on LH release mediated by TPA alone. This suggests that synergism is mediated via calmodulin and not a direct effect of calcium on protein kinase C.