Early detection and integrated care for adolescents and young adults with psychotic disorders: the ACCESS III study.

OBJECTIVE: The objective of the study was to investigate whether a combined intervention composed of early detection plus integrated care (EDIC) enhances outcomes in patients with early psychosis compared to standard care (SC). METHODS: ACCESS III is a prospective non-randomized historical control design 1-year study examining the efficacy of EDIC (n = 120) vs. SC (n = 105) in patients aged 12-29 years. Primary outcome was the rate of ≥6 months combined symptomatic and functional remission. Additional outcomes comprised the reduction of DUP and course of psychopathology, functioning, quality of life, and satisfaction with care. RESULTS: In observed cases, 48.9% in the EDIC and 15.2% in the SC group reached the primary endpoint. Remission was predicted by EDIC (OR = 6.8, CI: 3.15-14.53, P < 0.001); younger age predicted non-remission (OR = 1.1, CI: 1.01-1.19, P = 0.038). Linear regressions indicated a reduction of DUP in EDIC (P < 0.001), but not in SC (P = 0.41). MMRMs showed significantly larger improvements in PANSS positive (P < 0.001) and GAF (P < 0.01) scores in EDIC vs. SC, and in EDIC over time in CGI-Severity (P < 0.001) and numerically in Q-LES-Q-18 (P = 0.052). CONCLUSIONS: EDIC lead to significantly higher proportions of patients achieving combined remission. Moderating variables included a reduction of DUP and EDIC, offering psychotherapeutic interventions.

Evidence for enzootic circulation of Rift Valley fever virus among livestock in Cameroon.

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen, causing serious epidemics in Africa and the Arabian Peninsula. In Cameroon serological data indicate the presence of RVFV, but active circulation of RVFV, causing clinical infections has not been proven yet. For this purpose we carried out a serological and molecular study on a total of 1953 randomly selected serum samples of small ruminants and cattle, which were collected in years 2013 and 2014 in Cameroon. In a first step, sera were screened serologically using a variety of assay formats to reveal RVFV specific antibodies. At the second stage, seropositive specimen were assessed for acute RVFV infections via IgM-specific ELISA and quantitative real-time RT-PCR. Our data show a significant difference in the antibody prevalence in cattle (13.5% [95% confidence interval: 11.4-15.7]) and small ruminants (3.4% [95% confidence interval: 2.3-4.7]), with indications for annual fluctuations and significant regional differences of seropositivity. One small ruminant and three bovines were eventually found to be positive in IgM ELISA and indications for viremia were found in one bovine by RVFV genome detection using quantitative real-time RT-PCR. The results of this study therefore corroborate the presence of acute RVFV-infection and its circulation in Cameroon.

Genetic Characterization of Circulating African Swine Fever Viruses in Nigeria (2007-2015).

Sequencing and analysis of three discrete genome regions of African swine fever viruses (ASFV) from archival samples collected in 2007-2011 and active and passive surveillance between 2012 and 2015 in Nigeria were carried out. Analysis was conducted by genotyping of three single-copy African swine fever (ASF) genes. The E183L and B646L genes that encode structural proteins p54 and p72, respectively, were utilized to delineate genotypes before intragenotypic resolution by characterization of the tetrameric amino acid repeat region within the hypervariable central variable region of the B602L gene. The results showed no variation in the p72 and p54 gene regions sequenced. Phylogeny of p72 sequences revealed that all the Nigerian isolates belonged to genotype I, while that of the p54 recovered the Ia genotype. Analysis of B602L gene revealed the differences in the number of tetrameric repeats. Four new variants (Tet-15, Tet-17a, Tet-17b and Tet-48) were recovered, while a fifth variant (Tet-20) was the most widely distributed in the country displacing Tet-36 reported previously in 2003-2006. The viruses responsible for ASF outbreaks in Nigeria are from very closely related but mutated variants of the virus that have been circulating since 1997. A practical implication of the genetic variability of the Nigerian viral isolates in this study is the need for continuous sampling and analysis of circulating viruses, which will provide epidemiological information on the evolution of ASFV in the field versus new incursion for informed strategic control of the disease in the country.

Prevalence and risk factors for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infection in pregnant women in Papua New Guinea.

OBJECTIVE: To determine the prevalence of, and risk factors associated with, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infection in pregnant women in Madang, Papua New Guinea (PNG). METHODS: A cross-sectional survey was conducted among 400 pregnant women presenting to antenatal clinics. Sociodemographic and behavioural data were collected and real-time PCR diagnostic methods were used to detect the presence of chlamydia, gonorrhoea and trichomonas in self-collected vaginal swabs. The relationships between symptoms, sociodemographic and behavioural factors and infection were assessed. RESULTS: The prevalence of C. trachomatis was 11.1%, N. gonorrhoeae was 9.7% and T. vaginalis was 21.3%. One-third of women (33.7%) had at least one infection. The most common symptom was abdominal pain (48.0%), but only abnormal vaginal discharge was consistently associated with infection (p<0.001). Women diagnosed with vaginal discharge syndrome were more likely to have at least one treatable infection (50.0% (47/94)  vs 26.8% (68/254), p<0.001), yet 59.1% of women with infection would have been missed by the current clinically-based syndromic diagnosis. Risk factors included having a partner at perceived risk of infection, maternal extramarital intercourse, early sexual debut, lack of formal education, urban residence and smoking. 78.8% of women reported never using condoms. CONCLUSIONS: The prevalences of T. vaginalis, C. trachomatis and N. gonorrhoeae were high among pregnant women in coastal PNG. The poor performance of clinically based syndromic diagnosis suggests that alternative strategies are urgently required to improve detection and reduce the burden of sexually transmitted infections and their associated adverse pregnancy outcomes in this population.

[Participatory Quality Development: Engaging Community Members in All Phases of Project Planning and Implementation]. / Partizipative Qualitätsentwicklung: Zielgruppen in alle Phasen der Projektgestaltung einbeziehen.

Community participation, recognised as a central feature of successful health promotion and prevention, is often difficult to implement. In this research project internationally recognised methods of participatory health research were applied to demonstrate ways in which community members can be engaged. Participatory health research is characterised by a close collaboration between academic researchers, practitioners and community members in order to generate common knowledge. It is not a question of translating knowledge from research into practice, but rather a question of promoting a collective learning process on the part of all participants for the purpose of developing solutions which address the interests and needs of local people. The result of the project is a new approach for strengthening the quality of prevention and health promotion interventions: participatory quality development (PQD).

Development and validation of a 3ABC antibody ELISA in Australia for foot and mouth disease.

OBJECTIVE: To measure the diagnostic performance of an Australian-developed ELISA for the detection of antibodies against the non-structural proteins (NSP) 3ABC of the foot and mouth disease (FMD) virus. DESIGN: Test development and validation study. METHODS: The diagnostic specificity was determined using 2535 sera from naïve animals and 1112 sera from vaccinated animals. Diagnostic sensitivity was calculated from the data for 995 sera from experimentally and field-infected animals from FMD-endemic countries in South East Asia. A commercial ELISA detecting antibodies against FMD virus NSP was used as the reference test to establish relative sensitivity and specificity. Bayesian latent class analysis was performed to corroborate results. The diagnostic window and rate of detection were determined at different times using sera from cattle, sheep and pigs before and after infection, and after vaccination and subsequent infection. Repeatability and reproducibility data were established. RESULTS: At 35% test cut-off, the 3ABC ELISA had an overall diagnostic sensitivity of 91.5% and diagnostic specificity of 96.4%. The diagnostic sensitivity in vaccinated and subsequently infected cattle was 68.4% and diagnostic specificity in vaccinated cattle was 98.0%. CONCLUSIONS: The 3ABC ELISA identified field and experimentally infected animals, as well as vaccinated and subsequently infected animals. Diagnostic sensitivity and specificity estimates for other FMD NSP tests are comparable with the results obtained in this study. This NSP ELISA was found to be 'fit for purpose' as a screening assay at the herd level to detect viral infection and also to substantiate absence of infection.

Women's satisfaction and symptoms following NovaSure endometrial ablation: a postal questionnaire survey in Lothian, Scotland.

Impedance-controlled endometrial ablation (NovaSure) is commonly used to treat premenopausal heavy menstrual bleeding in Lothian, Scotland. Using postal questionnaires, we assessed patient satisfaction, treatment success and post-procedure symptoms in a cohort of women who had NovaSure treatment between January 2007 and May 2009. The response rate was 61.2% (115/188): 90.4% (104/115) of women were satisfied and would recommend the procedure; 36.8% (42/114) of women were amenorrhoeic at follow-up (mean = 497 days) and NovaSure significantly improved levels of both menstrual bleeding and pain (p < 0.01). Of the women, 67.0% (77/115) reported symptoms such as discomfort, vaginal discharge and bleeding/spotting within 6 weeks following NovaSure. A total of 13.9% (16/115) required further treatment following NovaSure, including hysterectomy. Patient satisfaction with NovaSure was high. Preoperative counselling needs to include information on character and duration of postoperative symptoms. Future research could compare patient satisfaction and clinical outcomes between NovaSure and the levonorgestrel-releasing intrauterine system.

[Memorandum prevention research - research areas and methods]. / Memorandum zur Präventionsforschung - Themenfelder und Methoden (Langfassung).

From 2004 to 2012, the German Ministry of Education and Research (BMBF) established its first funding programme for the promotion of prevention research. 60 projects on primary prevention and health promotion and the meta-project entitled "Cooperation for Sustainable Prevention Research" (KNP) received BMBF grants under this programme during this period. The experience and knowledge gained and recommendations arising from the research funded under this programme are compiled in memorandum format. The "Memorandum on Prevention Research - Research Areas and Methods" highlights 5 research areas that are considered to be especially relevant from the perspective of the involved scientists and practice partners.The promotion of structural development and sustainability enhancement in disease prevention and health promotion are central areas that should branch out from existing nuclei of crystallization. Improving the health competence of the population and of specific subpopulations is another major area. Research in these areas should contribute to the development of theoretical concepts and to the empirical testing of these concepts. The transfer of knowledge for effective use of developed disease prevention and health promotion programmes and measures is still a scarcely researched area. Among other things, studies of the transfer of programmes from one context to another, analyses of the coop-eration between politics and science, and the continued theoretical and conceptual development of transfer research are needed. Long-term data on the effects of intervention studies are also needed for proper evaluation of sustainability. The latter dem-onstrates the importance of method development in disease prevention and health promotion research as an area that should receive separate funding and support. This research should include, in particular, studies of the efficacy of complex interventions, health economic analyses, and participative health research.

Estrogenic regulation of S6K1 expression creates a positive regulatory loop in control of breast cancer cell proliferation.

The 40S ribosomal S6 kinase 1 (S6K1) is an important regulator of cell growth. Expression of S6K1 is often elevated in breast cancer cells. However, the transcriptional mechanism of S6K1 overexpression is not understood. In this report, we demonstrate that estrogen activates expression of S6K1 via estrogen receptor (ER)α in ER-positive breast cancer cells. We also show that estrogen acts on the proximal promoter of the S6K1 gene in a mechanism involving the transcriptional factor GATA-3. Finally, we provide data that support the importance of estrogenic regulation of S6K1 expression in breast cancer cell proliferation. S6K1 directly phosphorylates and regulates ligand-independent activity of ERα, while ERα upregulates S6K1 expression. This S6K1-ERα relationship creates a positive feed-forward loop in control of breast cancer cell proliferation. Furthermore, the co-dependent association between S6K1 and ERα may be exploited in the development of targeted breast cancer therapies.

INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model.

The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may provide enhanced antitumor activity of doxorubicin while improving the overall toxicity profile. Preclinically, INNO-206 has shown superior activity over doxorubicin in a murine renal cell carcinoma model and in breast carcinoma xenograft models. In this work, we compared the antitumor activity of INNO-206 and doxorubicin at their respective maximum tolerated doses in three additional xenograft models (breast carcinoma 3366, ovarian carcinoma A2780, and small cell lung cancer H209) as well as in an orthotopic pancreas carcinoma model (AsPC-1). INNO-206 showed more potent antitumor efficacy than free doxorubicin in all tumor models and is thus a promising clinical candidate for treating a broad range of solid tumors.

Maternal morbidity and mortality in peri-urban Kenya--assessing progress in improving maternal healthcare.

OBJECTIVE: Improving quality of maternal healthcare delivery is pivotal to reversing the trend of maternal health in developing countries and consequently, achieving the 5th millennium goal of reducing maternal mortality and improving universal access to reproductive health. Periodic facility-based reviews of maternal morbidity and mortality are crucial to improving quality of care delivered. METHODS: This retrospective study was conducted in PCEA Kikuyu Hospital, Kenya. Data on sociodemographics, recorded antenatal care activities, maternal morbidities and deaths were elicited from case notes of all pregnancies and births over a 2 year period and subsequently analyzed. RESULTS: There were 1716 deliveries during the period. 1405 (91%) of the women booked for antenatal care; 1068 (57.3%) had at least 3 visits before delivery. 842 (45.9%) were either untested for Human Immunodeficiency Virus or their results were not documented; 55 (3%) tested positive. The caesarean section rate was 27.4% (n=470); PMTCT (Prevention of Mother to Child Transmission) constituted 1.6% (10) of the indications. Urinary tract infection was the commonest maternal illness in pregnancy (14.5%, n=270), however, it was not found to be associated with any adverse outcome. Genital tract trauma was the commonest morbidity suffered by the women during delivery (90.6%, n=800). Psychological disorders constituted 5.3% (7) of reported postpartum complications. There were 2 maternal deaths out of 1673 live births, giving a maternal mortality ratio of 119.55 per 100,000 live births. The deaths resulted from septic abortion and eclampsia. CONCLUSION: Urinary tract infection is an important cause of maternal illness during pregnancy. Routine screening is recommended. PMTCT needs further consolidation to increase the number of screened women and ensure those who need interventions like caesarean sections get access to them. Diagnosis and management of psychological disorders in pregnancy remain unsatisfactory. Further studies to identify the true burden of these conditions are needed.

International network for capacity building for the control of emerging viral vector-borne zoonotic diseases: ARBO-ZOONET.

Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different domestic and wild animals and in humans, posing a threat to public health because of their epidemic and zoonotic potential. In recent decades, the geographical distribution of these diseases has expanded. Outbreaks of WNF have already occurred in Europe, especially in the Mediterranean basin. Moreover, CCHF is endemic in many European countries and serious outbreaks have occurred, particularly in the Balkans, Turkey and Southern Federal Districts of Russia. In 2000, RVF was reported for the first time outside the African continent, with cases being confirmed in Saudi Arabia and Yemen. This spread was probably caused by ruminant trade and highlights that there is a threat of expansion of the virus into other parts of Asia and Europe. In the light of global warming and globalisation of trade and travel, public interest in emerging zoonotic diseases has increased. This is especially evident regarding the geographical spread of vector-borne diseases. A multi-disciplinary approach is now imperative, and groups need to collaborate in an integrated manner that includes vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions.

Prevalence of Brucella abortus antibodies in serum of Holstein cattle in Cameroon.

Holstein cattle of a small scale dairy production systems were screened for Brucella abortus antibodies in 21 villages in Cameroon by ELISA. Results show a general seroprevalence of 8.4% in Holstein cattle. Of the 192 cows tested, 14 were infected giving a within-sex seroprevalence of 7.3% while 6/74 bulls were infected with a seroprevalence of 8%. There was no evidence (P=0.11) of differences in seroprevalence between age groups although animals above one year and below three years accounted for nearly half of the infected animals. 64% of infected animals were found in three locations (P=0.015): Kutaba (32%), Bamendankwe (16%) and Finge (16%). A specific control programme should be organized at these locations. Measures should be taken to ensure the eradication of the disease within the population and sound control measures adopted to avoid a further spread of the disease to larger cattle populations. Infected animals should be slaughtered systematically. All farmers should be advised to boil milk before consumption. Vaccination against Brucella abortus should be instituted and use of artificial insemination propagated. In order to ensure a productive and healthy population of Holstein cows within the dairy production scheme, regular Brucella testing should be instituted.

[Participation in the cooperation between target group, project and sponsor]. / Partizipation in der Zusammenarbeit zwischen Zielgruppe, Projekt und Geldgeber.

The intrinsic connection between empowerment and participation is apparent in the Ottawa Charter on Health Promotion. In order for citizens to reach a higher degree of autonomy and control over health-related factors (empowerment) they need to have an active role in the decision-making processes affecting their lives and the environment in which they live (participation). This implies that many decisions are made affecting the health of citizens over which they have no influence. The question is: Who has the power to make such decisions and how can this power be shared more equitably? This question can be raised not only at the highest political level, but also locally in the context of the collaboration between various stake-holders. The local level plays a key role in deciding which health promotion measures are developed and funded, thus contributing in an important way to strengthening communities. In this article the method "Circles of Decision-Making" is presented as a tool for assisting those working at the local level in determining to what degree the active participation of the various stake-holders has been achieved and in what ways the participation of those "on the outside" of decision-making processes can be strengthened. This method is based on the concept of Participatory Quality Development (PQD) created by the authors and their community partners. PQD uses methods from community-based research to address issues of quality in community-level health promotion and prevention.

Development and evaluation of a loop-mediated isothermal amplification method for diagnosis of tropical theileriosis.

A loop-mediated isothermal amplification (LAMP) assay was developed and evaluated for diagnosis of tropical theileriosis. A set of six primers was designed based on the unique gene of Theileria annulata (Theileria annulata strain Ankara hypothetical protein (GeneDB TA04795). The protocol for the reaction was setup and the specificity and sensitivity of the assay were established. The specificity experiment showed that LAMP primers amplified T. annulata DNA successfully, while no amplification was seen for Theileria parva, Theileria mutans, Theileria sergenti, Theileria sinensis, Babesia bovis as well as bovine genomic DNA and water control. When the sensitivity of LAMP assay was compared with that of conventional PCR a 10-fold higher sensitivity was found, with a detection limit of 10 pg/microl of genomic DNA isolated from a T. annulata-infected cell line. The LAMP product was confirmed by restriction digestion and staining with SYBR Green I. Furthermore, the LAMP assay was applied for the diagnosis of T. annulata in field samples and compared with reverse line blot (RLB), demonstrating that results of the LAMP assay corresponded to those of RLB. These results indicate that the LAMP assay is rapid and simple to run, cost-effective, sensitive and specific and has potential usefulness for application in epidemiological studies on T. annulata infection of cattle.

The International Atomic Energy Agency (IAEA) experience in the development of validation systems leading to the OIE certification of diagnostic assays.

For the past 15 years, the International Atomic Energy Agency (IAEA) has had a major interest in helping its member states to diagnose livestock diseases through the development and validation of diagnostic tests for trans-boundary animal diseases. In November, 2007, an IAEA consultants meeting attended by experts, OIE members and producers reviewed the OIE process for the recognition of tests to date. Conclusions concerning the application procedure were tabled by the general meeting and then specific producer recommendations were made. Both are shown below, along with conclusions regarding referencing in general. Some of the points brought up suggest major changes in the idea of trade prescription and test status.

[Early diagnosis of depression by the family physician]. / Depressive Erkrankung. Wie Sie zur richtigen Diagnose finden.

For patients with a depressive disorder, the family physician is often the first contact person. The doctor's early diagnosis and rapid initiation of treatment are hence of crucial importance. Because patients usually present with physical symptoms, the physician must actively explore the possibility of a depression; this means that the doctor must specifically ask about the principle symptoms and also explicitly address the subject of suicidal tendencies. The clarification of the course of depression (monophasic, recurrent or bipolar) and the exclusion physical causes are additional elements of the diagnosis. A screening is helpful for making a diagnosis, but does not replace a clinical examination.

Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain.

Lentiviral vectors have proven to be promising tools for transduction of brain cells in vivo and in vitro. In this study, we have examined the central nervous system (CNS) transduction efficiencies and patterns of a self-inactivating simian immunodeficiency virus (SIVmac)-derived lentiviral vector pseudotyped with glycoproteins from the vesicular stomatitis virus (VSV-G), the amphotropic murine leukemia virus (MLV4070Aenv), the lymphocytic choriomeningitis virus (LCMV-GP), the Ross River virus (RRV-GP) and the rabies virus (RV-G). All glycoproteins were efficiently incorporated into SIV virions, allowing efficient transduction of neuronal cell lines as well as of primary dissociated mouse brain cell cultures. After injection of highly concentrated vector stocks into the striatum of adult mice, quantitative analyses revealed high transduction efficiency with VSV-G pseudotypes, while LCMV-GP and RV-G pseudotypes exhibited moderate transduction efficiencies. MLV4070Aenv and RRV-GP pseudotypes, however, showed only weak levels of transduction after stereotactic injection into the brain. Regarding cell tropism in vivo, VSV-G-pseudotyped SIV vectors transduced neuronal as well as glial cells, whereas all other pseudotypes preferentially transduced neuroglial cells. In addition, we analyzed the influence of the central polypurine tract (cPPT) in context of the VSV-G-pseudotyped SIV transfer vector for infection of brain cells. Deletion of the cPPT sequence from the transfer vector decreased the in vivo transduction efficiency by fourfold, and, more importantly, this modification changed the transduction pattern, since these vectors were no longer able to infect neuronal cells in vivo. Vector injection into the brain did elicit a humoral immune response in the injected hemisphere; however, no gross signs of inflammation could be detected. Analysis of the biodistribution of the vector revealed that, besides the injected brain region, no vector-specific sequences could be detected in any of the organs evaluated. These data indicate SIV vectors as efficient gene delivery vehicles for the treatment of neurodegenerative diseases.

Aspects of kit validation for tests used for the diagnosis and surveillance of livestock diseases: producer and end-user responsibilities.

The Joint Food and Agriculture Organization/International Atomic Energy Agency (IAEA) Division of Nuclear Techniques in Food and Agriculture, based at the IAEA in Vienna, Austria, has extensive experience in helping to develop and validate assays and has provided strong support in developing World Organisation for Animal Health (OIE) norms. This paper will focus on enzyme-linked immunosorbent assay and polymerase chain reaction as the major technologies exploited in diagnosis and surveillance. Problems involving the terminology and factors in kit production, supply and validation are examined, in particular emphasising the importance of robustness and ruggedness of tests. The authors discuss the responsibilities of the various stakeholders (producers, distributors, users, and national/international organisations) in achieving quality controlled data to solve diagnostic and surveillance problems. The roles of internal quality control (internal proficiency testing) and external quality assurance (external proficiency testing) as well as aids to solving problems with kits are examined.