Use of test accuracy study design labels in NICE's diagnostic guidance.

BACKGROUND: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. OBJECTIVES: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. METHODS: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. RESULTS: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. CONCLUSION: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.

Hybrid Oleate-Iodide Ligand Shell for Air-Stable PbSe Nanocrystals and Superstructures.

A postsynthetic treatment is presented to improve the air stability of PbSe nanocrystals (NCs) and PbSe square superstructures. The addition of z-type Pb(oleate)2 ligands together with x-type iodide ligands creates a hybrid ligand shell containing both ligands. The air stability of the PbSe NCs is checked by enduring absorption spectroscopy under ambient conditions. With a combined NaI + Pb(oleate)2 treatment, the absorption spectrum remains unchanged for several days under ambient conditions. Fourier transform infrared spectroscopy shows that the surface coordination of the oleate ligands changes by the chemical treatment: from mixed chelating bidentate + bridging to Pb for the pristine nanocrystals to almost exclusive chelating bidentate coordination after chemical passivation. The shift of the C-H stretching vibration shows that the oleate hydrocarbon layer is in a more liquidlike state after the chemical treatment, suggesting that oleate and iodide ligands are often present on adjacent surface positions.

Genetic admixture supports an ancient hybrid origin of the endangered Hawaiian duck.

Speciation is regarded primarily as a bifurcation from an ancestral species into two distinct taxonomic units, but gene flow can create complex signals of phylogenetic relationships, especially among different loci. We evaluated several hypotheses that could account for phylogenetic discord between mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA) within Hawaiian duck (Anas wyvilliana), including stochastic lineage sorting, mtDNA capture and widespread genomic introgression. Our results best support the hypothesis that the contemporary Hawaiian duck is descended from an ancient hybridization event between the mallard (Anas platyrhynchos) and Laysan duck (Anas laysanensis). Whereas mtDNA clearly shows a sister relationship between Hawaiian duck and mallard, nuDNA is consistent with a genetic mosaic with nearly equal contributions from Laysan duck and mallard. In addition, coalescent analyses suggest that gene flow from either mallard or Laysan duck, depending on the predefined tree topology, is necessary to explain contemporary genetic diversity in Hawaiian ducks, and these estimates are more consistent with ancient, rather than contemporary, hybridization. Time since divergence estimates suggest that the genetic admixture event occurred around the Pleistocene-Holocene boundary, which is further supported by circumstantial evidence from the Hawaiian subfossil record. Although the extent of reproductive isolation from either putative parental taxon is not currently known, these species are phenotypically, genetically and ecologically different, and they meet primary criteria used in avian taxonomy for species designation. Thus, the available data are consistent with an admixed origin and support the hypothesis that the Hawaiian duck may represent a young hybrid species.

Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma development in the zebrafish optic pathway.

Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma pathogenesis. Yet, the role of this pathway in gliomagenesis remains controversial because of the lack of relevant animal models. Using the cytokeratin 5 promoter, we ectopically expressed a constitutively active zebrafish Smoothened (Smoa1) in neural progenitor cells and analyzed tumorigenic capacity of activated Shh signaling in both transient and stable transgenic fish. Transient transgenic fish overexpressing Smoa1 developed retinal and brain tumors, suggesting smoa1 is oncogenic in the zebrafish central nervous system (CNS). We further established stable transgenic lines that simultaneously developed optic pathway glioma (OPG) and various retinal tumors. In one of these lines, up to 80% of F1 and F2 fish developed tumors within 1 year of age. Microarray analysis of tumor samples showed upregulated expression of genes involved in the cell cycle, cancer signaling and Shh downstream targets ptc1, gli1 and gli2a. Tumors also exhibited specific gene signatures characteristic of radial glia and progenitor cells as transcriptions of radial glia genes cyp19a1b, s100ß, blbp, gfap and the stem/progenitor genes nestin and sox2 were significantly upregulated. Overexpression of GFAP, S100ß, BLBP and Sox2 was confirmed by immunofluorescence. We also detected overexpression of Mdm2 throughout the optic pathway in fish with OPG, therefore implicating the Mdm2-Tp53 pathway in glioma pathogenesis. In conclusion, we demonstrate that activated Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first OPG model not associated with neurofibromatosis 1.

Prenatal negative life events increases cord blood IgE: interactions with dust mite allergen and maternal atopy.

BACKGROUND: Prenatal exposure to both stress and aeroallergens (dust mite) may modulate the fetal immune system. These exposures may interact to affect the newborn immune response. We examined associations between prenatal maternal stress and cord blood total IgE in 403 predominately low-income minority infants enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project. We also examined potential modifying effects of maternal atopy and maternal dust mite exposure. METHODS: The Crisis in Family Systems survey was administered to mothers prenatally, and a negative life event domain score was derived to characterize stress. Dust mite allergen was quantified in dust from pregnant mothers' bedrooms. Cord blood was analyzed for total IgE. Using linear regression, we modeled the relationship of stress with cord blood IgE and interactions of stress with dust mite and/or maternal atopy, adjusting for potential confounders. RESULTS: Higher prenatal maternal stress (ß = 0.09; P = 0.01) was associated with increased cord blood IgE. The interactive effects between stress and dust mite groups (high vs low) were significantly different for children of atopic vs nonatopic mothers (P for three-way interaction = 0.005). Among children of atopic mothers, the positive association between stress and IgE was stronger in the high dust mite group. In children of mothers without a history of atopy, the positive association between stress and IgE was most evident in the low allergen group. CONCLUSIONS: Prenatal stress was independently associated with elevated cord blood IgE. Mechanisms underlying stress effects on fetal immunomodulation may differ based on maternal atopic status.

Ambiguous genitalia in a fertile, unilaterally cryptorchid male miniature schnauzer dog.

A 7-year-old male miniature schnauzer dog with unilateral cryptorchidism was presented for elective orchiectomy. Surgery to remove the cryptorchid testis revealed a fully formed uterus with horns attached to both testis and the body and cervix terminating at the prostate gland. The gross and microscopic diagnosis for the genital tract was persistent Müllerian duct syndrome with unilateral cryptorchidism. Additional associated lesions included cystic endometrial hyperplasia and a solitary, intratubular seminoma within the undescended testis. Persistent Müllerian duct syndrome is rare among domestic animals but is more common in miniature schnauzer dogs because of inheritance as an autosomal recessive trait.

[Interest of BNP value after cardiac resynchronisation therapy]. / Intérêt du dosage du "brain natriuretic peptide" (BNP) après resynchronisation cardiaque.

Cardiac resynchronisation therapy (CRT) induces, among responders, an early but sustained decrease of BNP levels. The changes of this parameter at 6 months, as well as its relative variations over the same time period, allow identification of the patients susceptible to benefit from CRT. Measurements of BNP levels might offer a useful tool for treatment optimisation in this particularly frail group of patients.

The relationship between vascular expansion of the aorta and pulmonary artery and the genesis of the impedance cardiogram using the technique of sonomicrometry.

PRIMARY OBJECTIVE: This prospective animal study aims to evaluate the contribution of the pulmonary artery (PA) and aorta on the morphology of the impedance cardiogram using sonomicrometry. METHODS: Impedance electrodes were placed around the thorax, aorta and in the oesophagus of five dogs. Sonomicrometry crystals were mounted on the PA and aorta for tracking vascular distension while a Doppler flow probe measured aortic blood flow. RESULTS: No significant differences (p > 0.05) were recorded between the onset of aortic expansion, aortic blood flow and the start of the impedance dZ/dt signal. Significant differences (p > 0.001) were recorded between the onset of PA expansion and the dZ/dt signal. PA expansion began 41.6 +/- 6.0 ms, 60.7 +/- 7.2 ms and 42.2 +/- 4.9 ms respectively, before surface, aortic and oesophageal impedance recordings. CONCLUSION: The genesis of the impedance cardiogram is attributed to volumetric expansion of the aorta.

The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis.

AIM: To conduct a systematic literature review in order to estimate the prevalence and odds ratio of clinically relevant depression in adults with Type 2 diabetes compared with those without. METHODS: MEDLINE, EMBASE and PSYCINFO databases were searched using MeSH terms and free text to identify relevant controlled studies. Published reference lists were also examined. Study selection and appraisal were conducted independently by two reviewers and a meta-analysis was performed to synthesize and analyse the data. RESULTS: Ten controlled studies including a total of 51 331 people were published between January 1980 and May 2005. The prevalence of depression was significantly higher in patients with Type 2 diabetes compared with those without [17.6 vs. 9.8%, OR = 1.6, 95%, confidence interval (CI) 1.2-2.0]. However, in most studies, patients with diabetes differed from those without on variables known to be associated with an increased risk of depression. The prevalence of depression was higher in females with diabetes (23.8%) compared with males (12.8%); however, the odds ratio for depression in patients with Type 2 diabetes compared with those without was higher in males (OR = 1.9, 95% CI 1.7-2.1) than females (OR = 1.3, 95% CI 1.2-1.4). Failure to report potential confounders prevented a more rigorous meta-analysis of risk. CONCLUSION: We identified raised rates of depression in people with Type 2 diabetes, however, there is a need for well-controlled and better-reported studies to inform the development of effective treatments for depression in these patients.

The outcome of renal denervation for managing loin pain haematuria syndrome.

OBJECTIVE: To evaluate the outcome of renal denervation for the treatment of loin pain-haematuria syndrome (LPHS), a rare syndrome of unknown cause associated with debilitating and intractable loin pain. PATIENTS AND METHODS: The case notes of 32 patients having 41 renal denervations were reviewed. Data collected included patient demographics, possible causes, cure or not after renal denervation, time to recurrence of pain after denervation and further operative intervention for managing LPHS. RESULTS: Full data were available for 24 patients (13 women; median age 43 years, range 28-74) having 33 denervations (eight bilateral and one repeat) with a median follow-up of 39.5 months. Most patients had no identifiable underlying cause although many had initially been diagnosed as having stone disease (42%) or pyelonephritis (25%), but with no corroborative evidence. All patients had been extensively investigated and had normal urine samples and cytology, and no abnormality on intravenous urography, renal tract ultrasonography and isotopic renography. Twenty-four renal denervations (73%) were followed by recurrent ipsilateral pain at a median (range) of 11 (0-120) months after surgery. Nine denervations (25%) in six men and two women were curative (median follow-up 16.5 months). Of those with recurrent pain, nine (38%) proceeded to nephrectomy, of whom three then developed loin pain on the contralateral side and two developed disabling wound pain. The analgesic requirement was less after eight non-curative denervations. There were no significant postoperative complications. CONCLUSIONS: Renal denervation has only a 25% success rate for managing pain associated with LPHS and should be used cautiously for this indication. Men had more benefit from the treatment; a third of patients had less requirement for analgesic after non-curative denervation.

An AFLP-based genome-wide mapping strategy.

To efficiently determine the chromosomal location of phenotypic mutants, we designed a genome-wide mapping strategy that can be used in any crop for which a dense AFLP (Amplified Fragment Length Polymorphism) map is available or can be made. The AFLP technique is particularly suitable to initiate map-based cloning projects because it detects many markers per reaction. First a standard set of AFLP primer combinations that results in a framework of AFLP markers well dispersed over the genome is selected. These primer combinations are applied to a limited number of mutant individuals from a segregating population to register linkage and non-linkage of the AFLP markers to the gene-of-interest. Further delineation of the area of interest is accomplished by analyzing the remaining recombinants and additional mutant individuals with AFLP markers that lie within the identified region. We illustrate the usefulness of the method by mapping three rotunda ( ron) leaf-form mutant loci of Arabidopsis thaliana and show that in the initial phase of map-based cloning projects a 400-600 kb interval can be identified for the average mutant locus within a few weeks. Once such an area is identified and before initiating the more time-consuming fine-mapping procedure, it is essential to examine publicly available databases for candidate genes and known mutants in the identified region. The 390-kb interval on chromosome 4 that harbors the ron2 mutation, also carries a known flower mutant, leunig ( lug); upon crossing, the two mutants appeared to be allelic. When no such candidates are found, the mapping procedure should be continued. We present a strategy to efficiently select recombinants that can be used for fine mapping.

Management of colonic injury following percutaneous nephrolithotomy.

Injury to the colon during percutaneous nephrolithotomy is rare. There are no definitive management guidelines for this injury. We report a case of left-sided colonic injury diagnosed following percutaneous nephrolithotomy and suggest a treatment algorithm.

Intratesticular lipoma.

Benign intratesticular lesions are rare. We describe the second reported case of an intratesticular lipoma and discuss the limitations of ultrasonography in differentiating benign from malignant conditions occurring within the testis.

A physical amplified fragment-length polymorphism map of Arabidopsis.

We have positioned amplified fragment-length polymorphism (AFLP) markers directly on the genome sequence of a complex organism, Arabidopsis, by combining gel-based AFLP analysis with in silico restriction fragment analysis using the published genome sequence. For placement of the markers, we used information on restriction fragment size, four selective nucleotides, and the rough genetic position of the markers as deduced from the analysis of a limited number of Columbia (Col)/Landsberg (Ler) recombinant inbred lines. This approach allows for exact physical positioning of markers as opposed to the statistical localization resulting from traditional genetic mapping procedures. In addition, it is fast because no extensive segregation analysis is needed. In principle, the method can be applied to all organisms for which a complete or nearly complete genome sequence is available. We have located 1,267 AFLP Col/Ler markers resulting from 256 SacI+2, MseI+2 primer combinations to a physical position on the Arabidopsis genome. The positioning was verified by sequence analysis of 70 markers and by segregation analysis of two leaf-form mutants. Approximately 50% of the mapped Col/Ler AFLP markers can be used for segregation analysis in Col/C24, Col/Wassilewskija, or Col/Cape Verde Islands crosses. We present data on one such cross: the localization of a viviparous-like mutant segregating in a Col/C24 cross.