Kanamycin resistance during in vitro development of pollen from transgenic tomato plants

Effects of kanamycin on pollen germination and tube growth of pollen from non-transformed plants and from transgenic tomato plants containing a chimaeric kanamycin resistance gene were determined. Germination of pollen was not affected by the addition of kanamycin to the medium in both genotypes. Kanamycin, however, severely affected tube growth of pollen from non-transformed plants, while pollen from plants containing the chimaeric gene were less sensitive and produced significantly longer tubes at kanamycin concentrations between 200-400 mg l-1. Apparently, this resistance for kanamycin correlates with the expression of the chimaeric gene during male gametophytic development.

Variations in hospital standardised mortality ratios (HSMR) as a result of frequent readmissions

BACKGROUND: We investigated the impact that variations in the frequency of readmissions had upon a hospital's standardised mortality ratio (HSMR). An adapted HSMR model was used in the study. Our calculations were based on the admissions of 70 hospitals in The Netherlands during the years 2005 to 2009. METHODS: Through a retrospective analysis of routinely collected hospital data, we calculated standardised in-hospital mortality ratios both by hospital and by diagnostic group (H/SMRs) using two different models. The first was the Dutch 2010 model while the second was the same model but with an additional adjustment for the readmission frequency. We compared H/SMR outcomes and the corresponding quality metrics in order to test discrimination (c-statistics), calibration (Hosmer-Lemeshow) and explanatory power (pseudo-R2 statistic) for both models. RESULTS: The SMR outcomes for model 2 compared to model 1, varied between -39% and +110%. On the HSMR level these variations ranged from -12% to +11%. There was a substantial disagreement between the models with respect to significant death on the SMR level as well as the HSMR level (~ 20%). All quality metrics comparing both models were in favour of model 2. The susceptibility to adjustment for readmission increased for longer review periods. CONCLUSIONS: The 2010 HSMR model for the Netherlands was sensitive to adjustment for the frequency of readmissions. A model without this adjustment, as opposed to a model with the adjustment, produced substantially different HSMR outcomes. The uncertainty introduced by these differences exceeded the uncertainty indicated by the 95% confidence intervals. Therefore an adjustment for the frequency of readmissions should be considered in The Netherlands, since such a model showed more favourable quality metric characteristics compared to a model without such an adjustment. Other countries could well benefit from a similar adjustment to their models. A review period of the data collected over the last three years, at least, is advisable. (aut.ref.

Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study)

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Although results of case series support the use of spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain, no confirmatory randomized controlled trial has been undertaken in this patient group to date. PROMISE is a multicenter, prospective, randomized, open-label, parallel-group study designed to compare the clinical effectiveness of spinal cord stimulation plus optimal medical management with optimal medical management alone in patients with failed back surgery syndrome and predominant low back pain. METHOD/DESIGN: Patients will be recruited in approximately 30 centers across Canada, Europe, and the United States. Eligible patients with low back pain exceeding leg pain and an average Numeric Pain Rating Scale score ≥5 for low back pain will be randomized 1:1 to spinal cord stimulation plus optimal medical management or to optimal medical management alone. The investigators will tailor individual optimal medical management treatment plans to their patients. Excluded from study treatments are intrathecal drug delivery, peripheral nerve stimulation, back surgery related to the original back pain complaint, and experimental therapies. Patients randomized to the spinal cord stimulation group will undergo trial stimulation, and if they achieve adequate low back pain relief a neurostimulation system using the Specify® 5-6-5 multi-column lead (Medtronic Inc., Minneapolis, MN, USA) will be implanted to capture low back pain preferentially in these patients. Outcome assessment will occur at baseline (pre-randomization) and at 1, 3, 6, 9, 12, 18, and 24 months post randomization. After the 6-month visit, patients can change treatment to that received by the other randomized group. The primary outcome is the proportion of patients with ≥50% reduction in low back pain at the 6-month visit. Additional outcomes include changes in low back and leg pain, functional disability, health-related quality of life, return to work, healthcare utilization including medication usage, and patient satisfaction. Data on adverse events will be collected. The primary analysis will follow the intention-to-treat principle. Healthcare use data will be used to assess costs and long-term cost-effectiveness. DISCUSSION: Recruitment began in January 2013 and will continue until 2016. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01697358 (http://www.clinicaltrials.gov).The study is funded by Medtronic In

Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

\ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment

Informality, violence, and disaster risks: Coproducing inclusive early warning and response systems in urban informal settlements in Honduras

Anticipatory disaster risk reduction (DRR) is an essential human right for the ~1 billion people living in informal settlements who are disproportionately exposed to climate-related hazards due to their high vulnerability. Participatory approaches are recognized as being critical for effective and sustainable disaster prevention, mitigation, and preparation through to response, but research on how to coproduce anticipatory DRR with people living and working in informal settlements is scant. Their exclusion is even more pronounced in challenging contexts, such as those characterized by social-political fragility and violence. As a result, a significant portion of the global population is left behind in best practices tied to global DRR ambitions, with DRR actions working neither with nor for the people most at risk. The signal case of urban informal settlements controlled by territorial gangs in Tegucigalpa, Honduras, illustrates the need for new thinking on how to inclusively mitigate, prepare for, and respond to natural hazard-related disasters. Our research examines the coproduction of early warning systems linked with response capacities for floods and landslides through the case study of the international NGO GOAL's work across the city with a focus on nine urban informal settlements with high levels of territorial gang violence. We explore how GOAL navigated informality and violent conflict to support the early warning and response system as an inclusive social process rather than a technical exercise. We identify four cross-cutting strategies employed by GOAL in support of local vulnerability reduction and capacity building based on a local systems approach. This research breaks new ground in identifying how to bridge the gap between knowledge and action in designing inclusive and sustainable early warning and response systems together with the millions of people around the world affected by the intersection of informality, violence, and disaster risks

Cross validation of bi-modal health-related stress assessment

This study explores the feasibility of objective and ubiquitous stress assessment. 25 post-traumatic stress disorder patients participated in a controlled storytelling (ST) study and an ecologically valid reliving (RL) study. The two studies were meant to represent an early and a late therapy session, and each consisted of a "happy" and a "stress triggering" part. Two instruments were chosen to assess the stress level of the patients at various point in time during therapy: (i) speech, used as an objective and ubiquitous stress indicator and (ii) the subjective unit of distress (SUD), a clinically validated Likert scale. In total, 13 statistical parameters were derived from each of five speech features: amplitude, zero-crossings, power, high-frequency power, and pitch. To model the emotional state of the patients, 28 parameters were selected from this set by means of a linear regression model and, subsequently, compressed into 11 principal components. The SUD and speech model were cross-validated, using 3 machine learning algorithms. Between 90% (2 SUD levels) and 39% (10 SUD levels) correct classification was achieved. The two sessions could be discriminated in 89% (for ST) and 77% (for RL) of the cases. This report fills a gap between laboratory and clinical studies, and its results emphasize the usefulness of Computer Aided Diagnostics (CAD) for mental health care

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of premedication regimens

Hypersensitivity reactions (HSRs) to paclitaxel are frequently encountered in patients receiving this antitumour drug. Administration of histamine H1- and H2-receptor antagonists and corticosteroids has been shown to reduce significantly the risk of developing an HSR in patients receiving taxanes. In this case report, we describe the fatal outcome of an HSR in a patient receiving paclitaxel despite short-course premedication. The level of evidence supporting the short-course i.v. premedication schedule is challenged, as it is not compatible with the pharmacokinetic properties of dexamethasone