A re-examination of otoconia from the Shaker mouse

We have studied saccular and utricular otoconia from Shaker-1 and Shaker-2 mice by X-ray diffraction and scanning electron microscopy. In contrast to previous reports, we found that the crystals were composed of calcite rather than poly crystalline hydroxylapatite. These crystals were indistinguishable mineralogically and morphologically from normal mouse otoconia. The reported occurrence of hydroxylapatite otoconia in the Shaker mouse is probably false.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47271/1/405_2004_Article_BF00464412.pd

Increased retention of functional fusions to toxic genes in new two-hybrid libraries of the E. coli strain MG1655 and B. subtilis strain 168 genomes, prepared without passaging through E. coli

BACKGROUND: Cloning of genes in expression libraries, such as the yeast two-hybrid system (Y2H), is based on the assumption that the loss of target genes is minimal, or at worst, managable. However, the expression of genes or gene fragments that are capable of interacting with E. coli or yeast gene products in these systems has been shown to be growth inhibitory, and therefore these clones are underrepresented (or completely lost) in the amplified library. RESULTS: Analysis of candidate genes as Y2H fusion constructs has shown that, while stable in E. coli and yeast for genetic studies, they are rapidly lost in growth conditions for genomic libraries. This includes the rapid loss of a fragment of the E. coli cell division gene ftsZ which encodes the binding site for ZipA and FtsA. Expression of this clone causes slower growth in E. coli. This clone is also rapidly lost in yeast, when expressed from a GAL1 promoter, relative to a vector control, but is stable when the promoter is repressed. We have demonstrated in this report that the construction of libraries for the E. coli and B. subtilis genomes without passaging through E. coli is practical, but the number of transformants is less than for libraries cloned using E. coli as a host. Analysis of several clones in the libraries that are strongly growth inhibitory in E. coli include genes for many essential cellular processes, such as transcription, translation, cell division, and transport. CONCLUSION: Expression of Y2H clones capable of interacting with E. coli and yeast targets are rapidly lost, causing a loss of complexity. The strategy for preparing Y2H libraries described here allows the retention of genes that are toxic when inappropriately expressed in E. coli, or yeast, including many genes that represent potential antibacterial targets. While these methods are generally applicable to the generation of Y2H libraries from any source, including mammalian and plant genomes, the potential of functional clones interacting with host proteins to inhibit growth would make this approach most relevant for the study of prokaryotic genomes

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

<b>Background</b><p></p> To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.<p></p> <b>Methods</b><p></p> An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.<p></p> <b>Results</b><p></p> The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.<p></p> <b>Conclusions</b><p></p> It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC

Chronic non-transmural infarction has a delayed recovery of function following revascularization

<p>Abstract</p> <p>Background</p> <p>The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic non-transmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization.</p> <p>Methods</p> <p>Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).</p> <p>Results</p> <p>Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 ± 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001).</p> <p>Conclusions</p> <p>Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.</p

Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication: a systematic review and meta-analysis

Item does not contain fulltextINTRODUCTION: Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all systematic reviews, randomized clinical trials and prospective cohort series to quantify the effectiveness of IPDs and to evaluate the potential side-effects. METHODS: Data from all studies prospectively describing clinical results based on validated outcome scales and reporting complications of treatment of patients with INC with IPD placement. We searched MEDLINE, EMBASE, Web of Science, Cochrane (CENTRAL), CINAHL, Academic Search Premier, Science Direct up to July 2010. Studies describing patients with INC caused by lumbar stenosis, reporting complication rate and reporting based on validated outcome scores, were eligible. Studies with only instrumented IPD results were excluded. RESULTS: Eleven studies eligible studies were identified. Two independently RCTs and eight prospective cohorts were available. In total 563 patients were treated with IPDs. All studies showed improvement in validated outcome scores after 6 weeks and 1 year. Pooled data based on the Zurich Claudication Questionnaire of the RCTs were more in favor of IPD treatment compared with conservative treatment (pooled estimate 23.2, SD 18.5-27.8). Statistical heterogeneity after pooled data was low (I-squared 0.0, p = 0.930). Overall complication rate was 7%. CONCLUSION: As the evidence is relatively low and the costs are high, more thorough (cost-) effectiveness studies should be performed before worldwide implementation is introduced

Helper Response to Experimentally Manipulated Predation Risk in the Cooperatively Breeding Cichlid Neolamprologus pulcher

Background We manipulated predation risk in a field experiment with the cooperatively breeding cichlid Neolamprologus pulcher by releasing no predator, a medium- or a large-sized fish predator inside underwater cages enclosing two to three natural groups. We assessed whether helpers changed their helping behaviour, and whether within-group conflict changed, depending on these treatments, testing three hypotheses: ‘pay-to-stay’ PS, ‘risk avoidance’ RA, or (future) reproductive benefits RB. We also assessed whether helper food intake was reduced under risk, because this might reduce investments in other behaviours to save energy. Methodology/Principal Findings Medium and large helpers fed less under predation risk. Despite this effect helpers invested more in territory defence, but not territory maintenance, under the risk of predation (supporting PS). Experimentally covering only the breeding shelter with sand induced more helper digging under predation risk compared to the control treatment (supporting PS). Aggression towards the introduced predator did not differ between the two predator treatments and increased with group member size and group size (supporting PS and RA). Large helpers increased their help ratio (helping effort/breeder aggression received, ‘punishment’ by the dominant pair in the group) in the predation treatments compared to the control treatment, suggesting they were more willing to PS. Medium helpers did not show such effects. Large helpers also showed a higher submission ratio (submission/ breeder aggression received) in all treatments, compared to the medium helpers (supporting PS). Conclusions/Significance We conclude that predation risk reduces helper food intake, but despite this effect, helpers were more willing to support the breeders, supporting PS. Effects of breeder punishment suggests that PS might be more important for large compared to the medium helpers. Evidence for RA was also detected. Finally, the results were inconsistent with RB

The Felix-trial. Double-blind randomization of interspinous implant or bony decompression for treatment of spinal stenosis related intermittent neurogenic claudication

Abstract. Background. Decompressive laminotomy is the standard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication. New techniques, such as interspinous process implants, claim a shorter hospital stay, less post-operative pain and equal long-term functional outcome. A comparative (cost-) effectiveness study has not been performed yet. This protocol describes the design of a randomized controlled trial (RCT) on (cost-) effectiveness of the use of interspinous process implants versus conventi