Evaluation of the WHO laboratory quality stepwise implementation tool.

OBJECTIVES: To introduce the Laboratory Quality Stepwise Implementation (LQSI) tool and provide data about its roll-out, usage and effectiveness in assisting laboratories with quality improvement. METHODS: The LQSI tool, a freely available stepwise guide, was developed by WHO to assist laboratories with efficiently implementing a quality management system. RESULTS: Since the tool's launch in 2014, it has been accessed by 130 986 unique users from 195 of 206 listed states. Of 35 respondents to a survey, 12 (34%) indicated that their laboratory had been able to achieve accreditation/certification/licensing as a result of using the tool. CONCLUSIONS: The LQSI tool, currently being used worldwide and available in English, French, Russian, Spanish, Arabic and Turkish, positively impacts the quality of services provided by clinical and public health laboratories, leading to improved clinical care and disease surveillance capacity as required by the IHR (2005) and envisioned by the Global Health Security Agenda.

Vocal acoustics in the endangered proboscis monkey (Nasalis larvatus).

The endangered proboscis monkey (Nasalis larvatus) is a sexually highly dimorphic Old World primate endemic to the island of Borneo. Previous studies focused mainly on its ecology and behavior, but knowledge of its vocalizations is limited. The present study provides quantified information on vocal rate and on the vocal acoustics of the prominent calls of this species. We audio-recorded vocal behavior of 10 groups over two 4-month periods at the Lower Kinabatangan Wildlife Sanctuary in Sabah, Borneo. We observed monkeys and recorded calls in evening and morning sessions at sleeping trees along riverbanks. We found no differences in the vocal rate between evening and morning observation sessions. Based on multiparametric analysis, we identified acoustic features of the four common call-types "shrieks," "honks," "roars," and "brays." "Chorus" events were also noted in which multiple callers produced a mix of vocalizations. The four call-types were distinguishable based on a combination of fundamental frequency variation, call duration, and degree of voicing. Three of the call-types can be considered as "loud calls" and are therefore deemed promising candidates for non-invasive, vocalization-based monitoring of proboscis monkeys for conservation purposes.

Retention of prominin in microvilli reveals distinct cholesterol-based lipid micro-domains in the apical plasma membrane.

Membrane cholesterol-sphingolipid 'rafts', which are characterized by their insolubility in the non-ionic detergent Triton X-100 in the cold, have been implicated in the sorting of certain membrane proteins, such as placental alkaline phosphatase (PLAP), to the apical plasma membrane domain of epithelial cells. Here we show that prominin, an apically sorted pentaspan membrane protein, becomes associated in the trans-Golgi network with a lipid raft that is soluble in Triton X-100 but insoluble in another non-ionic detergent, Lubrol WX. At the cell surface, prominin remains insoluble in Lubrol WX and is selectively associated with microvilli, being largely segregated from the membrane subdomains containing PLAP. Cholesterol depletion results in the loss of prominin's microvillus-specific localization but does not lead to its complete intermixing with PLAP. We propose the coexistence within a membrane domain, such as the apical plasma membrane, of different cholesterol-based lipid rafts, which underlie the generation and maintenance of membrane subdomains.

Convergent antifouling activities of structurally distinct bioactive compounds synthesized within two sympatric Haliclona demosponges.

A wide range of sessile and sedentary marine invertebrates synthesize secondary metabolites that have potential as industrial antifoulants. These antifoulants tend to differ in structure, even between closely related species. Here, we determine if structurally divergent secondary metabolites produced within two sympatric haliclonid demosponges have similar effects on the larvae of a wide range of benthic competitors and potential fouling metazoans (ascidians, molluscs, bryozoans, polychaetes, and sponges). The sponges Haliclona sp. 628 and sp. 1031 synthesize the tetracyclic alkaloid, haliclonacyclamine A (HA), and the long chain alkyl amino alcohol, halaminol A (LA), respectively. Despite structural differences, HA and LA have identical effects on phylogenetically disparate ascidian larvae, inducing rapid larval settlement but preventing subsequent metamorphosis at precisely the same stage. HA and LA also have similar effects on sponge, polychaete, gastropod and bryozoan larvae, inhibiting both settlement and metamorphosis. Despite having identical roles in preventing fouling and colonisation, HA and LA differentially affect the physiology of cultured HeLa human cells, indicating they have different molecular targets. From these data, we infer that the secondary metabolites within marine sponges may emerge by varying evolutionary and biosynthetic trajectories that converge on specific ecological roles.

Development and application of SINE multilocus and quantitative genetic markers to study oilseed rape (Brassica napus L.) crops.

A genetic marker system based on the S1 Short Interspersed Elements (SINEs) in the important commercial crop, oilseed rape ( Brassica napus L.) has been developed. SINEs provided a successful multilocus, dominant marker system that was capable of clearly delineating winter- and spring-type crop varieties. Sixteen of 20 varieties tested showed unique profiles from the 17 polymorphic SINE markers generated. The 3' or 5' flank region of nine SINE markers were cloned, and DNA was sequenced. In addition, one putative pre-transposition SINE allele was cloned and sequenced. Two SINE flanking sequences were used to design real-time PCR assays. These quantitative SINE assays were applied to study the genetic structure of eight fields of oilseed rape crops. Studied fields were more genetically diverse than expected for the chosen loci (mean H T = 0.23). The spatial distribution of SINE marker frequencies was highly structured in some fields, suggesting locations of volunteer impurities within the crop. In one case, the assay identified a mislabeling of the crop variety. SINE markers were a useful tool for crop genetics, phylogenetics, variety identification, and purity analysis. The use and further application of quantitative, real-time PCR markers are discussed.

A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer.

A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 microg/m2 granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received > or =2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer.

Directed forgetting in animals.

Directed-forgetting research with animals suggests that animals show disrupted test performance only under certain conditions. Important variables are (a) whether during training, the cue to forget (F cue) signals nonreward (i.e., that the trial is over) versus reward (i.e., that reinforcement can be obtained) and (b) given that reinforcement can be obtained on F-cue trials, whether the post-F-cue response pattern is compatible with the baseline memory task. It is proposed that some findings of directed forgetting can be attributed to trained response biases, whereas others may be attributable perhaps to frustration-produced interference. It is suggested that directed forgetting in animals should be studied using procedures similar to those used to study directed forgetting in humans. This can be accomplished by presenting, within a trial, both to-be-remembered and to-be-forgotten material.

Does intermittent coronary perfusion offer greater myocardial protection than continuous aortic cross-clamping?

There has been considerable controversy concerning the relative merits of intermittent coronary perfusion vs. continuous aortic cross-clamping for cardiac procedures requiring ischemic arrest. Using the isovolumic ventricular balloon model and "stop-freeze" biopsy techniques, myocardial contractility (LV dp/dt max, length-tension, and force-velocity relationships) and metabolism (adenine nucleotides, creatine phosphate, and glycogen) were studied in 46 intact dogs supported by normothermic cardiopulmonary bypass and subjected to either 60 minutes of continuous ischemic arrest or to four 15-minute intervals of ischemia each followed by 5 minutes of reperfusion. Following ischemia the hearts were reperfused for 30 minutes and defibrillated after the first 10 minutes. There were no significant differences in either metabolic parameters or contractile function between the groups. Although partial regeneration of adenosine triphosphate and glycogen occurred during reperfusion, only creatine phosphate achieved normal values and the end result was no difference between the two techniques. These data indicate that 5 minutes of coronary reperfusion between consecutive episodes of ischemic arrest affords no greater intraoperative protection of the myocardium than does continuous aortic cross-clamping.

Interruption of patent ductus arteriosus in premature infants with respiratory distress syndrome.

In infants with respiratory distress syndrome (RDS) hypoxemia inhibits closure of the patent ductus arteriosus (PDA), resulting in increased pulmonary blood flow with subsequent increased hypoxemia. In an attempt to interrupt this cycle 42 consecutive premature infants with RDS and PDA, weighing between 550 and 2,000 gm (average, 1,383 gm) and with an average gestational age of 31 weeks, were arbitrarily treated either medically (13 patients) or by interruption of the PDA (20 patients). Eleven patients who were initially treated medically could not be weaned from the respirator and later underwent operation. There were no operative or anesthetic deaths; late survival was 65% (20 patients). The last 31 patients were randomly divided into operative and nonoperative groups. Preliminary results revealed no significant differences in late survival between the two groups. Since the operative risk is minimal, further investigative efforts are indicated to settle this issue.

Value transfer in a simultaneous discrimination appears to result from within-event pavlovian conditioning.

When pigeons acquire a simple simultaneous discrimination, some of the value acquired by the S+ transfers to the S-. The mechanism underlying this transfer of value was examined in three experiments. In Experiment 1, pigeons trained on two simultaneous discriminations (A + B- and C +/- D-) showed a preference for B over D. This preference was reduced, however, following the devaluation of A. In Experiment 2, when after the same original training, value was given to D, the pigeons' preference for C did not significantly increase. In Experiment 3, when both discriminations involved partial reinforcement (S +/-), A + C- training resulted in a preference for B over D, whereas B + D- training resulted in a preference for A over C. Thus, simultaneous discrimination training appears to result in bidirectional within-event conditioning involving the S+ and S-.

Recent implementations of electronic medical records in four family practice residency programs.

Electronic medical records (EMRs) are increasingly replacing paper records, and many residency program directors are interested in incorporating EMR systems into their clinics. The authors describe their experiences implementing EMRs in their family practice residency programs; the four programs are the Eau Claire Family Practice Residency Program, the Galveston Family Practice Residency Program, the Mayo-Scottsdale Residency Program, and the Wyoming Valley Family Practice Residency. The authors provide background information about each program and an overview of the EMR systems; they then describe the implementation processes, addressing training, integration with other software- and paper-based systems, security, costs, and effects on patient volume and staffing levels. Finally, they discuss the general benefits of and barriers to EMR-system implementations, and make recommendations for other programs considering implementing EMRs.

Stress and family functioning among caregivers of persons with Parkinson's disease.

This study investigated components of caregiving that cause distress among Parkinson's caregivers and explored relationships between stress and family functioning. Fifty caregivers completed two self-report measures designed to assess caregiver stress and characteristics of the family environment. Differences in terms of family environment were found between caregivers who reported high and low stress. Certain aspects of caregiving were reported to be more distressing than others, and demographic characteristics were related to family functioning. Duration of the caregiving was not related to stress and there were no differences in family environment based on duration. These results have implications for clinical practice and the development of interventions for Parkinson's caregivers.

Psychosocial and developmental factors in failure to thrive: one- to three- year follow-up.

Fifteen infants and children with a diagnosis of failure to thrive (FTT) were followed at one to three years postdischarge. Data were gathered from in-home interviews, psychosocial questionnaires, measurement of present height and weight, and administration of the Developmental Profile. Nine of the 15 children were still failing to thrive; the other 6 were considered recovered. The nonthriving group consisted of three subgroups: (1) developmentally retarded, (2) organic basis FTT, and (3) psychosocial FTT. The developmentally retarded children were significantly different in that they required more attention, had greater constipation, and engaged in less tantrum behavior. Further, they were significantly more impaired in the physical, self-help, and social areas of development. The difficulties in diagnosis and treatment of FTT children are discussed. Suggestions for the enhancement of medical management of this complex and life-threatening disorder are offered.

Most directed forgetting in pigeons can be attributed to the absence of reinforcement on forget trials during training or to other procedural artifacts.

In research on directed forgetting in pigeons using delayed matching procedures, remember cues, presented in the delay interval between sample and comparisons, have been followed by comparisons (i.e., a memory test), whereas forget cues have been followed by one of a number of different sample-independent events. The source of directed forgetting in delayed matching to sample in pigeons was examined in a 2 x 2 design by independently manipulating whether or not forget-cue trials in training ended with reinforcement and whether or not forget-cue trials in training included a simultaneous discrimination (involving stimuli other than those used in the matching task). Results were consistent with the hypothesis that reinforced responding following forget cues is sufficient to eliminate performance deficits on forget-cue probe trials. Only when reinforcement was omitted on forget-cue trials in training (whether a discrimination was required or not) was there a decrement in accuracy on forget-cue probe trials. When reinforcement is present, however, the pattern of responding established during and following a forget cue in training may also play a role in the directed forgetting effect. These findings support the view that much of the evidence for directed forgetting using matching procedures may result from motivational and behavioral artifacts rather than the loss of memory.

Methods for siting emergency stomas in the absence of a stoma therapist.

INTRODUCTION: Stomas often have to be sited in emergencies by trainees who may have had little training in this. Emergency stomas and stomas where the site has not been marked preoperatively by a stoma therapist are more prone to complications. These complications may severely affect a patient's quality of life. Advice in the literature on how to best site stomas is conflicting. We compared two easy anatomical methods of siting stomas to sites chosen by a stoma therapist and looked at how this site was affected by the patients' body mass index (BMI). METHODS: Patients undergoing elective colorectal surgery were seen either pre or postoperatively. Each patient's BMI was recorded and the positions of three different potential stoma positions (site G: the gold standard, marked by a stoma therapist; site S: marked using a pair of scissors against the umbilicus; site H: halfway between the umbilicus and anterior superior iliac spine) were compared. RESULTS: The two fixed anatomical methods described (method S and method H) both gave poor results. The most common reason for poor siting was the proximity of a skin crease. There was a statistically significant correlation between the patient's BMI and the laterality of the gold standard site. CONCLUSIONS: The two simple anatomical methods described here do not provide a shortcut to effective siting. A more effective method may be calculating the laterality of the site using the patient's BMI, and then moving up/down to avoid a skin crease and improve the patient's view for changing the bag. This deserves further study.