Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness, Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods: We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Results: Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6- D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected 0 67delT, p.Trp24X, p.Val37lle, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro, Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27lle, p.Met34hr, p.Ala40Ala, and p.Gly160Ser. Two previously reported Mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. Conclusions: The present study demonstrates that Mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Do individuals in better condition survive for longer? Field survival estimates according to male alternative reproductive tactics and sex

There is a gap in terms of the supposed survival differences recorded in the field according to individual condition. This is partly due to our inability to assess survival in the wild. Here we applied modern statistical techniques to field-gathered data in two damselfly species whose males practice alternative reproductive tactics (ARTs) and whose indicators of condition in both sexes are known. In Paraphlebia zoe, there are two ART: a larger black-winged (BW) male which defends mating territories and a smaller hyaline-winged (HW) male that usually acts as a satellite. In this species, condition in both morphs is correlated with body size. In Calopteryx haemorrhoidalis, males follow tactics according to their condition with males in better condition practicing a territorial ART. In addition, in this species, condition correlates positively with wing pigmentation in both sexes. Our prediction for both species was that males practicing the territorial tactic will survive less longer than males using a nonterritorial tactic, and larger or more pigmented animals will survive for longer. In P. zoe, BW males survived less than females but did not differ from HW males, and not necessarily larger individuals survived for longer. In fact, size affected survival but only when group identity was analysed, showing a positive relationship in females and a slightly negative relationship in both male morphs. For C. haemorrhoidalis, survival was larger for more pigmented males and females, but size was not a good survival predictor. Our results partially confirm assumptions based on the maintenance of ARTs. Our results also indicate that female pigmentation, correlates with a fitness component - survival - as proposed by recent sexual selection ideas applied to females.

Alternative to the stroop color-word test for illiterate individuals

An alternative to the Stroop Color-Word Test (SCWT), denominated the Colored Numbers Test (CNT), was developed to evaluate the selective attention of illiterate individuals. A total of 30 volunteers with basic education (control group) and 30 illiterate volunteers (experimental group) performed the SCWT and the CNT. Volunteers had to name the color of the rectangles in the CNT neutral condition, and in the critical condition they had to either name the color of the numbers or, when the numbers were black, read the numbers. An interference index (II) was calculated for both tests by subtracting the time taken to complete the task in the neutral condition from the time taken to complete the task in the critical condition. The control group showed an II of 14.9s in the SCWT and of 19.1s in the CNT, and the experimental group, which practically presented no interference in the SCWT (II = 0.2s), showed an II of 18.7s in the CNT. These findings suggest that the CNT can he used to evaluate selective attention. Further work should confirm its validity. Its advantage over the SCWT is that it does not depend on the ability to read words, being then suitable for illiterate individuals.

Seroprevalence of Human Herpesvirus 8 Infection in Individuals From Health Care Centers in Mozambique: Potential for Endemic and Epidemic Kaposi`s Sarcoma

Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its prevalence in Mozambique is unknown. The seroprevalence of HHV-8 in a cohort of individuals seen at public health centers in Northern (n = 208), Central (n = 226), or Southern (n = 318) Mozambique was examined. All individuals were interviewed to obtain socioeconomic, demographic and clinical data and were tested for serum anti-HHV-8 antibodies using an immunofluorescence assay. The overall frequency of HHV-8 antibodies was 21.4% and, in spite of the diversity of epidemiological characteristics of the tested individuals, did not differ significantly among regions: 18.7%, 24.3% and 21.4% in the North, Center, and South, respectively (chi(2), 2.37; P = 0.305). The variables that were associated significantly with the presence of HHV-8 antibodies were gender, age, level of education, number of siblings and HIV serostatus, but these differed across the regions. In the North, although tested individuals lived under poor socioeconomic conditions, no association between HHV-8 infection and household variables was detected, with the exception of the number of siblings (P = 0.042). In the Central region, HHV-8 infection was associated with gender (P = 0.010), the number of household members (P = 0.031), and the place of attendance (P = 0.021). In the South, HHV-8 infection was associated with the number of siblings (P = 0.023) and HIV status (P = 0.002). The overall prevalence of HHV-8 seropositivity increased with age. These results demonstrate that Mozambique is another country in Africa with endemic HHV-8 infection, and, because of the AIDS epidemic, continued access to antiretroviral treatment is necessary to avert an outbreak of AIDS-Kaposi`s sarcoma. J. Med. Virol. 82:1216-1223, 2010. (C) 2010 Wiley-Liss, Inc.

Comparison of signal-to-cutoff values in first, second, and third generation enzyme immunoassays for the diagnosis of HTLV-1/2 infection in ""at-risk"" individuals from Sao Paulo, Brazil

Data obtained during routine diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) and 2 (HTLV-2) in ""at-risk"" individuals from Sao Paulo, Brazil using signal-to-cutoff (S/C) values obtained by first, second, and third generation enzyme immunoassay (EIA) kits, were compared. The highest S/C values were obtained with third generation EIA kits, but no correlation was detected between these values and specific antibody reactivity to HTLV-1, HTLV-2, or untyped HTLV (p = 0.302). In addition, use of these third generation kits resulted in HTLV-1/2 false-positive samples. In contrast, first and second generation EIA kits showed high specificity, and the second generation EIA kits showed the highest efficiency, despite lower S/C values. Using first and second generation EIA kits, significant differences in specific antibody detection of HTLV-1, relative to HTLV-2 (p = 0.019 for first generation and p < 0.001 for second generation EIA kits) and relative to untyped HTLV (p = 0.025 for first generation EIA kits), were observed. These results were explained by the composition and format of the assays. In addition, using receiver operating characteristics (ROC) analysis, a slight adjustment in cutoff values for third generation EIA kits improved their specificities and should be used when HTLV ""at-risk"" populations from this geographic area are to be evaluated. (C) 2009 Elsevier B.V. All rights reserved.

A Comparative Study of the Frequency of Antibody and Titers Against Human Herpesvirus 8 Latent and Lytic Antigens in ""At-Risk"" Individuals and Among Patients With Kaposi`s Sarcoma

Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi`s sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross-sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS-KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using ""in house"" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher`s exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different ""at-risk"" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS. J. Med. Virol. 81: 1292-1297, 2009. (C) 2009 Wiley-Liss, Inc.

A Bayesian model for estimating the malaria transition probabilities considering individuals lost to follow-up

It is known that patients may cease participating in a longitudinal study and become lost to follow-up. The objective of this article is to present a Bayesian model to estimate the malaria transition probabilities considering individuals lost to follow-up. We consider a homogeneous population, and it is assumed that the considered period of time is small enough to avoid two or more transitions from one state of health to another. The proposed model is based on a Gibbs sampling algorithm that uses information of lost to follow-up at the end of the longitudinal study. To simulate the unknown number of individuals with positive and negative states of malaria at the end of the study and lost to follow-up, two latent variables were introduced in the model. We used a real data set and a simulated data to illustrate the application of the methodology. The proposed model showed a good fit to these data sets, and the algorithm did not show problems of convergence or lack of identifiability. We conclude that the proposed model is a good alternative to estimate probabilities of transitions from one state of health to the other in studies with low adherence to follow-up.

Saliva flow rate, buffer capacity, and pH of autistic individuals

The objective of the study was to evaluate saliva flow rate, buffer capacity, pH levels, and dental caries experience (DCE) in autistic individuals, comparing the results with a control group (CG). The study was performed on 25 noninstitutionalized autistic boys, divided in two groups. G1 composed of ten children, ages 3-8. G2 composed of 15 adolescents ages 9-13. The CG was composed of 25 healthy boys, randomly selected and also divided in two groups: CG3 composed of 14 children ages 4-8, and CG4 composed of 11 adolescents ages 9-14. Whole saliva was collected under slight suction, and pH and buffer capacity were determined using a digital pHmeter. Buffer capacity was measured by titration using 0.01 N HCl, and the flow rate expressed in ml/min, and the DCE was expressed by decayed, missing, and filled teeth (permanent dentition [DMFT] and primary dentition [dmft]). Data were plotted and submitted to nonparametric (Kruskal-Wallis) and parametric (Student`s t test) statistical tests with a significance level less than 0.05. When comparing G1 and CG3, groups did not differ in flow rate, pH levels, buffer capacity, or DMFT. Groups G2 and CG4 differ significantly in pH (p = 0.007) and pHi = 7.0 (p = 0.001), with lower scores for G2. In autistic individuals aged 3-8 and 9-13, medicated or not, there was no significant statistical difference in flow rate, pH, and buffer capacity. The comparison of DCE among autistic children and CG children with deciduous (dmft) and mixed/permanent decayed, missing, and filled teeth (DMFT) did not show statistical difference (p = 0.743). Data suggest that autistic individuals have neither a higher flow rate nor a better buffer capacity. Similar DCE was observed in both groups studied.

Does the neuromotor abnormality type affect the salivary parameters in individuals with cerebral palsy?

Background: Previous studies reported alterations in salivary flow rate and biochemical parameters of saliva in cerebral palsy (CP) individuals; however, none of these considered the type of neuromotor abnormality among CP individuals, thus it remains unclear whether the different anatomical and extended regions of the brain lesions responsible for the neurological damage in CP might include disruption of the regulatory mechanism of saliva secretion as part of the encephalopathy. The aim of this study was to evaluate salivary flow rate, pH and buffer capacity in saliva of individuals with CP, aged 3-16 years, with spastic neuromotor abnormality type and clinical patterns of involvement. Methods: Sixty-seven individuals with CP spasticity movement disorder, were divided in two groups according to age (3-8- and 9-16-years-old) and compared with 35 sibling volunteers with no neurological damage, divided in two groups according to age (3-8- and 9-16-years-old). Whole saliva was collected under slight suction and pH and buffer capacity were determined using a digital pHmeter. Buffer capacity was measured by titration using 0.01N HCL, and flow rate was calculated in ml/min. Results: In both age groups studied, whole saliva flow rate, pH and buffer capacity were significantly lower in the spastic CP group (P < 0.05). The clinical patterns of involvement did not influence the studied parameters. Conclusion: These findings show that individuals with spastic cerebral palsy present lower salivary flow rate, pH and buffer capacity that can increase the risk of oral disease in this population.

Friskfaktorer på en enhet : Identifiera & fortsatt bevara

Detta är en kvalitativ studie med syftet att inom en enhet på Stockholms Stad identifiera friskfaktorer och undersöka vad som krävs för att fortsatt bevara dessa. Vidare är syftet att undersöka vilket stöd som är nödvändigt för bevarandet samt HR-funktionens roll i detta avseende. Enheten är, sett till sjukfrånvaro, en välmående grupp som står inför förändringar inom marknaden och målsättning då de påverkas av det nyligen genomförda regeringsskiftet. Ett frågeverktyg användes för att framställa de åtta viktigaste dimensionerna av det attraktiva arbetet och en fördjupad diskussion kring dessa fördes sedan under en fokusgruppsintervju tillsammans med enhetens medarbetare. Resultatet visade att de viktigaste dimensionerna var bland annat arbetstid och relationer. Vidare påvisades att en balans mellan arbetsliv och privatliv är av stor vikt för medarbetarnas hälsa och välmående. För att fortsatt bevara det attraktiva i arbetet visade empirin att gruppens relationer och ledaren var nyckelfaktorer och att HR-funktionen, den personalstrategiska avdelningen, enbart bidrar med en administrativ och vägledande roll i frågan om stöd. Arbetets slutsatser innefattar att bevarandet av friskfaktorer kräver att tillvaron måste vara begriplig, hanterlig och meningsfull men även att medarbetarna behöver rimliga krav i relation till deras handlingsutrymme. En vidare slutsats är behovet av en förändring i ledarskapsbeteendet i kommande stadier då gruppen eventuellt kommer att hamna i en ny mognadsfas på grund förändrade omständigheter. Författarna drar även slutsatsen att friskfaktorer är till viss del individuellt beroende på livssituation men att balansen mellan arbetsliv och privatliv är betydande för de flesta. HR-funktionen, den personalstrategiska avdelningen, har en informativ och administrativ roll i frågan om stöd och författarna anser att det ligger en logik i denna roll. Sett till organisationens storlek är det lättare att vända psykosociala frågor till företagshälsovård eller en psykologgrupp och få det arbetsrättsliga stödet eller information från HR-funktionen.

How does employment density influence individuals’ wages? : A micro data approach.

We estimate the effect of employment density on wages in Sweden in a large geocoded data set on individuals and workplaces. Employment density is measured in four circular zones around each individual’s place of living. The data contains a rich set of control variables that we use in an instrumental variables framework. Results show a relatively strong but rather local positive effect of employment density on wages. Beyond 5 kilometers the effect becomes negative. This might indicate that the effect of agglomeration economies falls faster with distance than the effects of congestion.

Mapas de Conhecimento: Em Busca de um Instrumento de Aplicação nas Organizações para Operacionalização da Gestão do Conhecimento

The present work consists on the development and exploration of a knowledge mapping model. It is aimed in presenting and testing that model in an exploratory manner for the operationalization in theoretical terms and its practical application. For this proposal, it approaches ¿knowledge management¿ by three dimensions of management: processes control, results control and leadership. Assuming the inherently personal character of knowledge and admitting the impossibility for the management to command the individuals knowledge mental processes, this study states the possibility for management to control the organizations information processes, to state and to monitor the objectives and to lead people. Therefore, the developed tool searches to graphically represent the people¿s knowledge, which becomes, consequently, information. Also it evaluates the individual¿s maturity against the identified knowledge and prescribes, according to the Situational Leadership Theory, a style of leadership in compliance with the respective maturities. The knowledge map considered here translates the graphical representation of the relevant knowledge that is said to reach the objectives of the organization. That fact allows the results management for two reasons: first, the knowledge items are directly or indirectly connected to an objective and second, the knowledge map developed indicates a importance grade of the identified knowledge for the main objective stated. The research strategy adopted to explore the model of knowledge mapping and to test its applicability, also identifying its possible contributions and limitations, is the Actionresearch. Following the research strategy¿s prescribed stages, the knowledge map, as considered by this study, was applied in a software development company to hospitals, clinics and restaurants management which is called ¿Tergus Systems and Consulting¿. More precisely, the knowledge map was applied in the customer support company¿s area for hospitals. The research¿s empirical evidences had concluded that the model is applicable with low level of complexity, but with great demand of time. The more important contributions are related to the identification of the relevant knowledge to the department objectives in set with a prescription of the knowledge capture and transference necessities, as well as, the orientation for the appropriate leadership style for each subordinate related to the knowledge item in question.

Um modelo de implementação do capability maturity model integration nível 2

Apesar de o CMMI (Capability Maturity Model Integration) prover uma cobertura mais detalhada do ciclo de vida dos produtos que o uso isolado de outros processos de melhoria, ainda assim não pode ser visto como uma metodologia pronta para ser utilizada pelas organizações. Cada organização deve mapear as áreas de processo do nível CMMI desejado (caso a opção seja a representação por estágios, como veremos adiante) à sua metodologia, aos seus métodos e técnicas de desenvolvimento de produtos e sistemas, levando também em consideração os objetivos de negócio da organização. Tanto o CMMI como as demais normas e modelos de qualidade, dizem “o que” e não “como” fazer. Determinar este “como” é um trabalho adicional bastante grande que as organizações devem realizar quando da adoção destas normas. Para isto, normalmente as organizações buscam no mercado empresas de consultoria que possuem experiência na área. Essas consultorias são bastante indicadas porque aumentam significativamente a qualidade e a velocidade dos resultados. Este trabalho pretende facilitar as organizações interessadas na implementação de um modelo de qualidade, fornecendo descrições sobre alguns dos modelos de qualidade mais utilizados atualmente, bem como modelos de processos, guias e formulários que podem ser utilizados diretamente ou como uma base para a implementação do modelo desejado. Embora se aplique à implementação de qualquer modelo de qualidade, mais especificamente, este trabalho destina-se a auxiliar organizações que visem implementar o modelo CMMI nível 2 (doravante usaremos também a abreviação CMMI-N2). Para tanto, descreve de forma mais detalhada este modelo e fornece um caminho para a implementação do mesmo, incluindo a descrição de um processo mínimo de desenvolvimento de software, com base no RUP (Rational Unified Process) e o uso de um modelo de ciclo de vida de melhoria de processos, o IDEAL. Neste trabalho, propõe-se que seja utilizado o modelo IDEAL para a implementação do modelo de qualidade devido ao fato de este modelo ter sido concebido originalmente como um modelo de ciclo de vida para melhoria de processos de software com base no SW-CMM (Capability Maturity Model for Software). Associado a esse modelo, é sugerido que se utilize algumas técnicas e processos de gerência de projetos para cada área de processo do CMMI-N2, visando implantar cada área de processo através de um projeto. Para a implementação são propostos guias, modelos (formulários) de implementação e uma tabela que mapeia todas as áreas de processo do CMMI-N2, seus objetivos, práticas, produtos de trabalho e as ferramentas associadas.

Influência da composição do grupo (turma escolar), entre crianças da primeira serie do 1. grau, sobre a estrutura sócio-afetiva

Neste estudo discutem-se as influências da forma de composição do grupo (turma escolar), entre crianças da primeira série do 1º Grau, em função da maturidade necessária à aprendizagem da leitura e da escrita, relativamente à estrutura e mudança da estrutura sócio-afetiva. O problema teve origem no questionamento em torno do valor da prática e suas possíveis influências sobre o desenvolvimento social da criança que, por volta dos sete anos de idade - coincidindo com a entrada para a escola - é mais fortemente incrementado. O suporte teórico do estudo é dado pela Teoria de Campo de Kurt Lewin. O percentual de indicações positivas (PIP) , o percentual de indicações negativas (PIN) , o destaque da posição sociométrica (D), a qualidade do destaque (Qd) , e a mudança das posições sociométricas dos indivíduos nos grupos (MPS) , - constituiram-se em indicadores da variável composição do grupo. Do estudo realizado conclui-se que as formas homogênea e heterogênea de composição do grupo influenciaram de maneira não significativamente diferente em relação à estrutura e a mudança da estrutura sócio-afetiva do grupo, sendo, portanto, injustificada a prática da homogeneização das classes escolares em relação a estes aspectos.