Chapter 7: Grading a Body of Evidence on Diagnostic Tests

10.1007/s11606-012-2021-9Journal of General Internal Medicine27SUPPL.1S47-S55JGIM

Novel use of a Weerda laryngoscope for transoral excision of a cervical ganglioneuroma: a case report

<p>Abstract</p> <p>Introduction</p> <p>A ganglioneuroma is a benign neoplasm arising from neural crest cells of the sympathetic nerve fibers and is most commonly seen in the posterior mediastinum or retroperitoneum. Although very uncommon, ganglioneuromas must be included in the differential diagnosis of neck masses. In young adult women, neck incisions made for excision of these benign tumors should be avoided whenever possible.</p> <p>Case presentation</p> <p>We herein describe the case of a 19-year-old Japanese woman with a ganglioneuroma. The tumor was found in the parapharyngeal space, an unusual location. A fine-needle aspiration biopsy was performed but was considered inadequate to make a definitive diagnosis, so the asymptomatic lesion was surgically excised using a Weerda laryngoscope. The lesion measured 4 × 3 cm in size and was encapsulated. A pathological analysis showed the presence of two distinct cell types, ganglion cells and Schwann cells, embedded in a loose myxoid stroma. The final diagnosis was a ganglioneuroma.</p> <p>Conclusion</p> <p>A complete excision was made possible by using a transoral approach with a novel use of the Weerda laryngoscope. Although its applicability to specific cases depends on the location, size and nature of the tumor, we believe that the Weerda laryngoscope will continue to be useful for performing transoral surgery for cervical tumors.</p

Infectious Disease Modeling of Social Contagion in Networks

Many behavioral phenomena have been found to spread interpersonally through social networks, in a manner similar to infectious diseases. An important difference between social contagion and traditional infectious diseases, however, is that behavioral phenomena can be acquired by non-social mechanisms as well as through social transmission. We introduce a novel theoretical framework for studying these phenomena (the SISa model) by adapting a classic disease model to include the possibility for ‘automatic’ (or ‘spontaneous’) non-social infection. We provide an example of the use of this framework by examining the spread of obesity in the Framingham Heart Study Network. The interaction assumptions of the model are validated using longitudinal network transmission data. We find that the current rate of becoming obese is 2 per year and increases by 0.5 percentage points for each obese social contact. The rate of recovering from obesity is 4 per year, and does not depend on the number of non-obese contacts. The model predicts a long-term obesity prevalence of approximately 42, and can be used to evaluate the effect of different interventions on steady-state obesity. Model predictions quantitatively reproduce the actual historical time course for the prevalence of obesity. We find that since the 1970s, the rate of recovery from obesity has remained relatively constant, while the rates of both spontaneous infection and transmission have steadily increased over time. This suggests that the obesity epidemic may be driven by increasing rates of becoming obese, both spontaneously and transmissively, rather than by decreasing rates of losing weight. A key feature of the SISa model is its ability to characterize the relative importance of social transmission by quantitatively comparing rates of spontaneous versus contagious infection. It provides a theoretical framework for studying the interpersonal spread of any state that may also arise spontaneously, such as emotions, behaviors, health states, ideas or diseases with reservoirs.National Institutes of Health (U.S.) (grant R01GM078986)National Science Foundation (U.S.)Bill & Melinda Gates FoundationTempleton FoundationNational Institute on Aging (grant P01 AG031093)Framingham Heart Study (contract number N01-HC-25195

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Gene Amplification, ABC Transporters and Cytochrome P450s: Unraveling the Molecular Basis of Pyrethroid Resistance in the Dengue Vector, Aedes aegypti

Dengue is the most rapidly spreading arboviral infection of humans and each year there are 50–100 million cases of dengue fever. There is no vaccine or drug to prevent dengue infection so control of the mosquitoes that transmit this virus is the only option to reduce transmission. Removing mosquito habitats close to human homes can be effective but in reality most dengue control programmes rely on a small number of chemical insecticides. Therefore, when the mosquito vectors develop resistance to the available insecticides, dengue control is jeopardized. In this study we examined the causes of resistance to the insecticide class most commonly used in mosquito control, the pyrethroids. We found that a group of genes, which have been implicated in detoxifying these insecticides in other populations of dengue vectors, were highly over expressed in both these Caribbean populations and we investigated the molecular basis of this increased expression. The next steps, which will be a considerable challenge, are to utilize this information to develop effective means of restoring insecticide susceptibility in dengue vectors

Underpinning Sustainable Vector Control through Informed Insecticide Resistance Management

Background: There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia’s programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. Methodology/Principal Findings: A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids,DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Conclusions/Significance: Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management pla

Novel Exon of Mammalian ADAR2 Extends Open Reading Frame

Background: The post-transcriptional processing of pre-mRNAs by RNA editing contributes significantly to the complexity of the mammalian transcriptome. RNA editing by site-selective A-to-I modification also regulates protein function through recoding of genomically specified sequences. The adenosine deaminase ADAR2 is the main enzyme responsible for recoding editing and loss of ADAR2 function in mice leads to a phenotype of epilepsy and premature death. Although A-to-I RNA editing is known to be subject to developmental and cell-type specific regulation, there is little knowledge regarding the mechanisms that regulate RNA editing in vivo. Therefore, the characterization of ADAR expression and identification of alternative ADAR variants is an important prerequisite for understanding the mechanisms for regulation of RNA editing and the causes for deregulation in disease. Methodology/Principal Findings: Here we present evidence for a new ADAR2 splice variant that extends the open reading frame of ADAR2 by 49 amino acids through the utilization of an exon located 18 kilobases upstream of the previously annotated first coding exon and driven by a candidate alternative promoter. Interestingly, the 49 amino acid extension harbors a sequence motif that is closely related to the R-domain of ADAR3 where it has been shown to function as a basic, single-stranded RNA binding domain. Quantitative expression analysis shows that expression of the novel ADAR2 splice variant is tissue specific being highest in the cerebellum

Differential Neuregulin 1 Cleavage in the Prefrontal Cortex and Hippocampus in Schizophrenia and Bipolar Disorder: Preliminary Findings

Neuregulin 1 (NRG1) is a key candidate susceptibility gene for both schizophrenia (SCZ) and bipolar disorder (BPD). The function of the NRG1 transmembrane proteins is regulated by cleavage. Alteration of membrane bound-NRG1 cleavage has been previously shown to be associated with behavioral impairments in mouse models lacking expression of NRG1-cleavage enzymes such as BACE1 and gamma secretase. We sought to determine whether alterations in NRG1 cleavage and associated enzymes occur in patients with SCZ and BPD.Using human postmortem brain, we evaluated protein expression of NRG1 cleavage products and enzymes that cleave at the external (BACE1, ADAM17, ADAM19) and internal (PS1-gamma secretase) sides of the cell membrane. We used three different cohorts (Controls, SCZ and BPD) and two distinct brain regions: BA9-prefrontal cortex (Controls (n = 6), SCZ (n = 6) and BPD (n = 6)) and hippocampus (Controls (n = 5), SCZ (n = 6) and BPD (n = 6)). In BA9, the ratio of the NRG1 N-terminal fragment relative to full length was significantly upregulated in the SCZ cohort (Bonferroni test, p = 0.011). ADAM17 was negatively correlated with full length NRG1 levels in the SCZ cohort (r = -0.926, p = 0.008). In the hippocampus we found significantly lower levels of a soluble 50 kDa NRG1 fragment in the two affected groups compared the control cohort (Bonferroni test, p = 0.0018). We also examined the relationship of specific symptomatology criteria with measures of NRG1 cleavage using the Bipolar Inventory of Signs and Symptoms Scale (BISS) and the Montgomery Åsberg Depression Rating Scale (MADRS). Our results showed a positive correlation between ADAM19 and psychosis (r = 0.595 p = 0.019); PS1 and mania (r = 0.535, p = 0.040); PS1 and depression (r = 0.567, p = 0.027) in BA9, and BACE1 with anxiety (r = 0.608, p = 0.03) in the hippocampus.Our preliminary findings suggest region-specific alterations in NRG1 cleavage in SCZ and BPD patients. These changes may be associated with specific symptoms in these psychiatric disorders

Leadership, staffing and quality of care in nursing homes

<p>Abstract</p> <p>Background</p> <p>Leadership and staffing are recognised as important factors for quality of care. This study examines the effects of ward leaders' task- and relationship-oriented leadership styles, staffing levels, ratio of registered nurses and ratio of unlicensed staff on three independent measures of quality of care.</p> <p>Methods</p> <p>A cross-sectional survey of forty nursing home wards throughout Norway was used to collect the data. Five sources of data were utilised: self-report questionnaires to 444 employees, interviews with and questionnaires to 13 nursing home directors and 40 ward managers, telephone interviews with 378 relatives and 900 hours of field observations. Separate multi-level analyses were conducted for quality of care assessed by relatives, staff and field observations respectively.</p> <p>Results</p> <p>Task-oriented leadership style had a significant positive relationship with two of the three quality of care indexes. In contrast, relationship-oriented leadership style was not significantly related to any of the indexes. The lack of significant effect for relationship-oriented leadership style was due to a strong correlation between the two leadership styles (<it>r </it>= 0.78). Staffing levels and ratio of registered nurses were not significantly related to any of the quality of care indexes. The ratio of unlicensed staff, however, showed a significant negative relationship to quality as assessed by relatives and field observations, but not to quality as assessed by staff.</p> <p>Conclusions</p> <p>Leaders in nursing homes should focus on active leadership and particularly task-oriented behaviour like structure, coordination, clarifying of staff roles and monitoring of operations to increase quality of care. Furthermore, nursing homes should minimize use of unlicensed staff and address factors related to high ratios of unlicensed staff, like low staff stability. The study indicates, however, that the relationship between staffing levels, ratio of registered nurses and quality of care is complex. Increasing staffing levels or the ratio of registered nurses alone is not likely sufficient for increasing quality of care.</p

Shedding Light on Vampires: The Phylogeny of Vampyrellid Amoebae Revisited

With the advent of molecular phylogenetic techniques the polyphyly of naked filose amoebae has been proven. They are interspersed in several supergroups of eukaryotes and most of them already found their place within the tree of life. Although the ‘vampire amoebae’ have attracted interest since the middle of the 19th century, the phylogenetic position and even the monophyly of this traditional group are still uncertain. In this study clonal co-cultures of eight algivorous vampyrellid amoebae and the respective food algae were established. Culture material was characterized morphologically and a molecular phylogeny was inferred using SSU rDNA sequence comparisons. We found that the limnetic, algivorous vampyrellid amoebae investigated in this study belong to a major clade within the Endomyxa Cavalier-Smith, 2002 (Cercozoa), grouping together with a few soil-dwelling taxa. They split into two robust clades, one containing species of the genus Vampyrella Cienkowski, 1865, the other containing the genus Leptophrys Hertwig & Lesser, 1874, together with terrestrial members. Supported by morphological data these clades are designated as the two families Vampyrellidae Zopf, 1885, and Leptophryidae fam. nov. Furthermore the order Vampyrellida West, 1901 was revised and now corresponds to the major vampyrellid clade within the Endomyxa, comprising the Vampyrellidae and Leptophryidae as well as several environmental sequences. In the light of the presented phylogenetic analyses morphological and ecological aspects, the feeding strategy and nutritional specialization within the vampyrellid amoebae are discussed