Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

A Brief History of Human Challenge Studies (1900-2021) Emphasising the Virology, Regulatory and Ethical Requirements, Raison D'etre, Ethnography, Selection of Volunteers and Unit Design.

Venetian quarantine 400 years ago was an important public health measure. Since 1900 this has been refined to include "challenge" or deliberate infection with pathogens be they viruses, bacteria, or parasites. Our focus is virology and ranges from the early experiments in Cuba with Yellow Fever Virus to the most widespread pathogen of our current times, COVID-19. The latter has so far caused over four million deaths worldwide and 190 million cases of the disease. Quarantine and challenge were also used to investigate the Spanish Influenza of 1918 which caused over 100 million deaths. We consider here the merits of the approach, that is the speeding up of knowledge in a practical sense leading to the more rapid licensing of vaccines and antimicrobials. At the core of quarantine and challenge initiatives is the design of the unit to allow safe confinement of the pathogen and protection of the staff. Most important though is the safety of volunteers. We can see now, as in 1900, that members of our society are prepared and willing to engage in these experiments for the public good. Our ethnology study, where the investigator observed the experiment from within the quarantine, gave us the first indication of changing attitudes amongst volunteers whilst in quarantine. These quarantine experiments, referred to as challenge studies, human infection studies, or "controlled human infection models" involve thousands of clinical samples taken over two to three weeks and can provide a wealth of immunological and molecular data on the infection itself and could allow the discovery of new targets for vaccines and therapeutics. The Yellow Fever studies from 121 years ago gave the impetus for development of a successful vaccine still used today whilst also uncovering the nature of the Yellow Fever agent, namely that it was a virus. We outline how carefully these experiments are approached and the necessity to have high quality units with self-contained air-flow along with extensive personal protective equipment for nursing and medical staff. Most important is the employment of highly trained scientific, medical and nursing staff. We face a future of emerging pathogens driven by the increasing global population, deforestation, climate change, antibiotic resistance and increased global travel. These emerging pathogens may be pathogens we currently are not aware of or have not caused outbreaks historically but could also be mutated forms of known pathogens including viruses such as influenza (H7N9, H5N1 etc.) and coronaviruses. This calls for challenge studies to be part of future pandemic preparedness as an additional tool to assist with the rapid development of broad-spectrum antimicrobials, immunomodulators and new vaccines.

Time-dependent cognitive and somatic symptoms of depression as predictors of new cardiac-related events in at-risk patients: the UPBEAT-UK cohort.

BACKGROUND: Evidence suggests that somatic rather than cognitive depressive symptoms are risk factors for recurrent cardiac events in at-risk patients. However, this has never been explored using a time-dependent approach in a narrow time-frame, allowing a cardiac event-free time-window. METHODS: The analysis was performed on 595 participants [70.6% male, median age 72 (27-98)] drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Depressive symptomatology was measured using the Patient Health Questionnaire-9 (PHQ-9) (four somatic, five cognitive items). New cardiac events (NCEs) including cardiac-related mortality were identified by expert examination of patient records. Analyses were performed using Cox proportional hazard models with delayed entry, with time-dependent depressive dimensions and covariates measured 12-18 months (median: 14.1, IQR: 3.5) prior to the event, with a 12-month cardiac event-free gap. RESULTS: There were 95 NCEs during the follow-up [median time-to-event from baseline: 22.3 months (IQR: 13.4)]. Both the somatic (HR 1.12, 95% CI 1.05-1.20, p = 0.001) and cognitive dimensions (HR 1.11, 95% CI 1.03-1.18, p = 0.004) were time-dependent risk factors for an NCE in the multi-adjusted models. Specific symptoms (poor appetite/overeating for the somatic dimension, hopelessness and feeling like a failure for the cognitive dimension) were also significantly associated. CONCLUSION: This is the first study of the association between depressive symptom dimensions and NCEs in at-risk patients using a time-to-event standardised approach. Both dimensions considered apart were independent predictors of an NCE, along with specific items, suggesting regular assessments and tailored interventions targeting specific depressive symptoms may help to prevent NCEs in at-risk populations.

Clinical calculator predictive of chemotherapy benefit in stage 1A uterine papillary serous cancers.

OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.

Synaptic activity protects against AD and FTD-like pathology via autophagic-lysosomal degradation.

Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein. In this study, we investigated the effect of synaptic stimulation on Tau pathology and synapses in in vivo and in vitro models of AD and frontotemporal dementia (FTD). We found that chronic DBS or chemically induced synaptic stimulation reduced accumulation of pathological forms of Tau and protected synapses, while chronic inhibition of synaptic activity worsened Tau pathology and caused detrimental effects on pre- and post-synaptic markers, suggesting that synapses are affected. Interestingly, degradation via the proteasomal system was not involved in the reduction of pathological Tau during stimulation. In contrast, chronic synaptic activation promoted clearance of Tau oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic activity resulted in opposite outcomes, with build-up of Tau oligomers in enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the negative effects of Tau in AD and FTD by acting on autophagy, providing a rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.

[Ability of French General Practitioners to detect common mental disorders identified using the Patient Health Questionnaire: Has this changed with the introduction of gatekeeping and registration with a chosen doctor?] / Détection par le médecin généraliste des troubles psychiatriques courants selon l'auto-questionnaire diagnostique le Patient Health Questionnaire : dix ans après, le dispositif du médecin traitant a-t-il modifié la donne ?

OBJECTIVES: The general practitioner (GP) is the most frequently consulted health professional by patients with common mental disorders (CMD). Yet approximately half of cases are not detected by the GP. Many factors linked to the patient, the doctor and the health care system influence detection. For example, detection rates are higher when patients are better known to their GP. On the other hand, patients visiting a different GP for reasons of dissatisfaction with previous care are more likely to be detected on the survey-day. In France, a form of gatekeeping was introduced in 2005 to encourage patients to register with a doctor (most often a GP) of their choice (known as the Preferred Doctor), responsible for care coordination and referral if necessary to secondary care. Visiting a different GP, other than for non-avoidable reasons (for e.g. GP unreachable, patient on holiday), is still possible but financially sanctioned with lower reimbursement rates. We aimed to compare GP detection rates before and after the introduction of this gatekeeping scheme. Patient service use behaviour such as doctor-shopping and GP referral to secondary care were also compared. METHODS: Two cross-sectional surveys using the same study methods were carried out 10 years apart. In 2003, 46 GPs and 1151 patients participated (approximately 25 patients per GP), with a 32.7% GP participation rate. In 2013, 38 GPs participated (of which 29 had participated in the previous study, with a 85.3% "recapture" rate) and 1133 patients (approximately 30 patients per GP). Patient participation rates were 89.8% and 67%, respectively. Patients completed self-report questionnaires in the waiting room of which the DSM-IV diagnostic criteria Patient Health Questionnaire (PHQ) and an adapted version of the Client Service Receipt Inventory (CSRI) on contacts with health care services in the previous six months. For each patient, the GP completed a questionnaire giving his rating of psychiatric illness on a five-point scale with his/her diagnosis for cases, and action undertaken. RESULTS: Of the patients, 27% and 25.4% had a CMD according to the PHQ (defined as a diagnosis of minor or major depression, panic attack, anxiety or somatoform disorder) in 2003 and 2013 respectively. Corresponding detection rates were 51% and 52.6%. Rates were highest for threshold disorders: panic disorder (69.4% and 79.9% in 2003 and 2013, respectively), major depression (75% and 63.3% in 2003 and 2013, respectively) and other anxiety disorders (69.1% and 78.8% in 2003 and 2013, respectively). In 2003, the GPs declared seeing 15.5% for the first time on the survey-day, compared to 9.6% in 2013 (P=0.006). Doctor-shopping declined between the two studies, from 18.4% to 12.1% for practical and mostly unavoidable reasons, and from 9.8% to 4.2% for dissatisfaction reasons (P<0.0001). Referral to specialist doctors increased from 9.7% in 2003 to 14.7% in 2013 (P=0.014). In 2013, on the survey-day, 94.8% of patients had registered with a Preferred Doctor and 81.2% were seeing this Preferred Doctor. In 2003, 93.5% of patients declared having a usual GP and 79.9% were visiting this GP on the survey-day. CONCLUSIONS: This is one of the first studies to report data from two repeated surveys carried out before and after a change in the health service organisation, with data collected from both the patient and the GP. We report relatively high GP detection rates for the two periods, with about 50% of CMDs, including subsyndromic conditions, detected by the GP. Rates are considerably higher for the threshold disorders. The overall detection rate did not increase as expected between the two studies. Detection is a complex topic, involving issues such as the suitability of applying categorical DSM-IV criteria diagnoses to primary care, the relevance of detecting subthreshold conditions and the ability of cross-sectional studies to correctly assess the ability of GPs to recognise cases. The introduction of gatekeeping with the choice of a Preferred Doctor has led to a decline in the frequency of doctor-shopping, whatever its reason, with patients no doubt being better known to the GP. Yet it appears most patients had already chosen a GP they were loyal to before the scheme, with a similar proportion of patients consulting their chosen GP or Preferred Doctor on both survey-days in 2003 and 2013, suggesting the scheme may to some extent only have officialised what already existed with respect to having a usual GP. The French reform still allows for doctor-shopping which can be considered as a positive aspect of the scheme: patients either dissatisfied with previous care or needing to change GP are thus able to "test" and choose the doctor that best suits their needs.

Real-Time Observation of Phonon-Mediated σ-π Interband Scattering in MgB_{2}.

In systems having an anisotropic electronic structure, such as the layered materials graphite, graphene, and cuprates, impulsive light excitation can coherently stimulate specific bosonic modes, with exotic consequences for the emergent electronic properties. Here we show that the population of E_{2g} phonons in the multiband superconductor MgB_{2} can be selectively enhanced by femtosecond laser pulses, leading to a transient control of the number of carriers in the σ-electronic subsystem. The nonequilibrium evolution of the material optical constants is followed in the spectral region sensitive to both the a- and c-axis plasma frequencies and modeled theoretically, revealing the details of the σ-π interband scattering mechanism in MgB_{2}.

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. Nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. Individuals who will go on to become symptomatic demonstrate increased circulating levels of interleukin (IL)-6, IL-8, IL-15, monocyte chemotactic protein (MCP)-1 and interferon (IFN) gamma-induced protein (IP)-10 as early as 12-29 h post-inoculation (during the presymptomatic phase), whereas challenged patients who remain asymptomatic do not. Overall, the immunological pathways of leucocyte recruitment, Toll-like receptor (TLR)-signalling, innate anti-viral immunity and fever production are all over-represented in symptomatic individuals very early in disease, but are also dynamic and evolve continuously over time. Comparison with simultaneous peripheral blood genomics demonstrates that some inflammatory mediators (MCP-1, IP-10, IL-15) are being expressed actively in circulating cells, while others (IL-6, IL-8, IFN-α and IFN-γ) are probable effectors produced locally at the site of infection. Interestingly, asymptomatic exposed subjects are not quiescent either immunologically or genomically, but instead exhibit early and persistent down-regulation of important inflammatory mediators in the periphery. The host inflammatory response to influenza infection is variable but robust, and evolves over time. These results offer critical insight into pathways driving influenza-related symptomatology and offer the potential to contribute to early detection and differentiation of infected hosts.

[Extension of mobile team services to the home: pilot project in the Vaud canton]. / Extension des prestations de type "équipe mobile" aux foyers socio-éducatifs: projet pilote dans le canton de Vaud.

The main objective of this project about mobile team service extension to the socio-educational home of the whole Vaud canton targets to decompartmentalize the socio-educational and youth-psychiatry domains. 64 patient were assessed during this pilot phase (after one-year functioning). In addition, a satisfaction survey was done either at the end of the follow up or at the end of the pilot phase of the project (31.12.2012). This experience was very positive as highlighted by the vast majority of the person involved in the socio-educational and youth-psychiatric domains taking care of youth. A desire of extension of mobile team service to other institutional structure or other situations was expressed.

Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133). AE were abstracted from the medical record using a structured instrument. SigAE were defined as an AE leading to MTX discontinuation. Covariates included: age, gender, race, RA antibody status, tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo comorbidity index, glucocorticoids, use of prior RA medications, and mean 4-variable disease activity score. Cox regression was performed to determine factors associated with time-to-SigAE. A p-value ≤ 0.005 established significance in the final model. RESULTS: The presence of ≥ 1 copy of the minor allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p-value 0.002 for heterozygotes and homozygotes for the minor allele, respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS: RA subjects taking MTX may have decreased time-to-SigAE with ≥ 1 copy of the minor allele in MTHFR rs1801131. Further investigation is warranted, as these SNPs may indicate susceptibility to MTX toxicity.

Time evolution of a Gaussian class of quasi-distribution functions under quadratic Hamiltonian.

A Lie algebraic method for propagation of the Wigner quasi-distribution function (QDF) under quadratic Hamiltonian was presented by Zoubi and Ben-Aryeh. We show that the same method can be used in order to propagate a rather general class of QDFs, which we call the "Gaussian class." This class contains as special cases the well-known Wigner, Husimi, Glauber, and Kirkwood-Rihaczek QDFs. We present some examples of the calculation of the time evolution of those functions.

Cognitive control in number magnitude processing: evidence from eye-tracking.

The unit-decade compatibility effect describes longer response times and higher error rates for incompatible (e.g., 37_52) than compatible (e.g., 42_57) number comparisons. Recent research indicated that the effect depends on the percentage of same-decade filler items. In the present study, we further examined this relationship by recording participants' eye-fixation behaviour. In four conditions, participants had to compare item sets with different filler item types (i.e., same-decade and same-unit filler items) and different numbers of same-decade filler items (i.e., 25, 50, and 75%). We found a weaker unit-decade compatibility effect with most fixations on tens in the condition with same-unit filler items. Moreover, the compatibility effect increased with the percentage of same-decade filler items which was accompanied by less fixations on tens and more fixations on units. Thus, our study provides first eye-tracking evidence for the influence of cognitive control in number processing.

Sex trafficking in Ireland from a health care perspective.

Sex trafficking within Ireland is a hidden phenomenon. In 2010, 78 alleged victims were reported to An Garda Siochina and the recorded levels of human trafficking into Ireland have remained at this level for the last four years. Despite this, no Irish guidelines or referral pathways exist to assist health care professionals. This paper highlights that health care professionals are not aware of this occurrence nor have they been trained to identify victims. Due to a lack of awareness many potential opportunities to detect these victims may be missed. While there is no single set of symptoms or signs that differentiates sex-trafficked victims from other sex workers, an awareness of common physical and psychological health problems associated with sex trafficking by health care professionals may increase victim detection rates. This paper summarises indicators, approach mechanisms, screening questions and a referral guideline relevant to the Irish health care system. This step-by-step guide can be used by health care professionals who encounter such a situation.

A survey investigating owner perceptions and management of firework-associated fear in dogs in the Greater Sydney area.

OBJECTIVE: To investigate the prevalence of firework-associated fear in dogs in Sydney, owner perception of their dog's response to fireworks, perceived efficacy of interventions to manage fearful behaviours and the frequency of dog owners seeking professional advice for these behaviours. METHODS: Dog owners in the Greater Sydney area were invited to complete an anonymous online survey. RESULTS: From 387 valid responses, 44.4% (171 of 385) reported their dogs were fearful of fireworks. The most common fear-related behaviour was seeking an owner or caretaker (120 of 161, 74.5%). Most owners responded by bringing their dog inside or trying to comfort or reassure their dog. Only 22.5% of owners sought professional advice for their dog's fear of fireworks, but of these, 65.5% considered that advice to be effective. Source and breed group were significantly associated with fear of fireworks (P = 0.011, P = 0.036 respectively). Fear of fireworks was also significantly associated with fear of thunder (P < 0.0001), gunshots (P < 0.0001) and vehicles (P = 0.0009). CONCLUSION: Fear of fireworks and other loud noises negatively impacts canine welfare, yet only a small percentage of owners sought professional advice. There is scope for veterinarians to educate owners and raise awareness about the identification and management of noise-associated fear and reduce the risk of escalation of fearful behaviours.

Characterizing and identifying incipient carious lesions in dental enamel using micro-Raman spectroscopy.

Early detection of dental caries is vital if improved patient outcomes are to be achieved by reversal of the demineralization process. Current techniques used by dentists for identifying carious lesions are effective in identifying more advanced lesions, but do not have sufficient sensitivity and specificity to detect them at the earliest stages. This study focused on characterizing the growth of incipient carious lesions in vitro using micro-Raman spectroscopy. The incipient carious lesions were grown on the buccal faces of human molars by controlled exposure to lactic acid. Lesions were cross-sectioned to expose the subsurface body of the lesion and then examined using micro-Raman spectroscopy. The intensity of the phosphate peaks in the Raman spectra was found to differ significantly between healthy enamel and the demineralized region of the lesions. The sensitivity of the phosphate peaks to the degree of demineralization was observed by taking a series of spectra over the cross section of the lesions. This revealed that the body of the lesion is highly demineralized, but in a narrow surface region (up to 10 µm) there is little demineralization. All the phosphate peaks were found to be sensitive to the degree of demineralization; however, changes in the intensity of the pronounced phosphate peak at 961 cm(-1) offer the most promise for identifying lesions. The results indicate that micro-Raman spectroscopy has both the sensitivity and selectivity to identify incipient carious lesions, but the presence of a surface layer with a relatively high mineral content could complicate the analysis.

Insecure attachment and frequent attendance in primary care: a longitudinal cohort study of medically unexplained symptom presentations in ten UK general practices.

BACKGROUND: In primary care frequent attenders with medically unexplained symptoms (MUS) pose a clinical and health resource challenge. We sought to understand these presentations in terms of the doctor-patient relationship, specifically to test the hypothesis that such patients have insecure emotional attachment. METHOD: We undertook a cohort follow-up study of 410 patients with MUS. Baseline questionnaires assessed adult attachment style, psychological distress, beliefs about the symptom, non-specific somatic symptoms, and physical function. A telephone interview following consultation assessed health worry, general practitioner (GP) management and satisfaction with consultation. The main outcome was annual GP consultation rate. RESULTS: Of consecutive attenders, 18% had an MUS. This group had a high mean consultation frequency of 5.24 [95% confidence interval (CI) 4.79-5.69] over the follow-up year. The prevalence of insecure attachment was 28 (95% CI 23-33) %. A significant association was found between insecure attachment style and frequent attendance, even after adjustment for sociodemographic characteristics, presence of chronic physical illness and baseline physical function [odds ratio (OR) 1.96 (95% CI 1.05-3.67)]. The association was particularly strong in those patients who believed that there was a physical cause for their initial MUS [OR 9.52 (95% CI 2.67-33.93)]. A possible model for the relationship between attachment style and frequent attendance is presented. CONCLUSIONS: Patients with MUS who attend frequently have insecure adult attachment styles, and their high consultation rate may therefore be conceptualized as pathological care-seeking behaviour linked to their insecure attachment. Understanding frequent attendance as pathological help seeking driven by difficulties in relating to caregiving figures may help doctors to manage their frequently attending patients in a different way.

Clinicians' attitudes to depression in Europe: a pooled analysis of Depression Attitude Questionnaire findings.

BACKGROUND: Depression in primary care is common but under-recognized and suboptimally managed. Health professionals' attitudes are likely to play an important part in their recognition and management of depression. OBJECTIVES: To pool findings from studies using the Depression Attitude Questionnaire (DAQ) to provide greater detail of clinicians' attitudes and the measure's psychometric properties. METHODS: Electronic databases and grey literature were searched for relevant studies. Data from eligible studies were requested and pooled analysis conducted. RESULTS: Twenty studies were eligible and data were obtained from 12 of these involving GPs (n = 1543) and nurses (n = 984). Responses showed strong disagreement that depression is due to ageing or weakness. European GPs were more positive about depression treatments than UK GPs; nurses were more favourable about psychotherapy than GPs. UK GPs especially strongly opposed notions that depression is best managed by psychiatrists. Trends over time indicated increasing acknowledgement of psychological therapies and the nurse's role in depression management. Factor analysis indicated that many DAQ items fitted weakly within an overall model. The most parsimonious solution involved two factors: a positive view of depression and its treatment response and professional confidence in depression management. CONCLUSIONS: Individual DAQ items appear to measure key aspects of clinicians' attitudes to depression, and item responses indicate important differences between professions and geographical settings as well as changes over time. There are problems with the DAQ as a scale: its internal consistency is weak, and several items appear specific to particular professions or service structures, indicating that this questionnaire should be revised.

Childhood sexual abuse and abnormal personality: a population-based study.

BACKGROUND: Childhood sexual abuse (CSA) has been shown to be a risk factor for personality disorder (PD). However, no previous studies have examined whether associations exist between sexual abuse and abnormal personality as measured both categorically and dimensionally. Such enquiry would more fully illuminate the impact of CSA on adult personality. METHOD: Using a large nationally representative sample, we set out to examine associations between CSA and categorically defined PD. We also examined associations between CSA and the five dimensions of personality (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism). A total of 1520 young adults were interviewed to determine the prevalence of sexual abuse occurring before age 16 years. A dimensional measure of personality was completed by 1469 participants, and 1145 had an informant-based PD assessment. RESULTS: PD was independently associated with repeated CSA [fully adjusted odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4]. Repeated sexual abuse was also associated with higher neuroticism and lower agreeableness (p values for both <0.001). Adjusting for the effects of potential confounders and mediators, including earlier symptoms of anxiety and depression, had little impact on the strength of associations. CONCLUSIONS: We conclude that repeated CSA is independently associated with categorically defined PD, and also with higher neuroticism and lower agreeableness. Our findings suggest that if a dimensional classification of PDs is adopted in future classification systems, there might be meaningful continuity with previous aetiological research conducted using the current categorical system.

HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.

Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.

Expression of pluripotency genes in buffalo (Bubalus bubalis) amniotic fluid cells.

Recent findings suggest that mammalian amniotic fluid (AF) is a source of multipotent stem cells (SCs), which can be used in regenerative medicine and assisted reproduction. We report the isolation, culture and characterization of amniotic fluid-derived cells from pregnant water buffalo uterus. These undifferentiated AF cells expanded without feeder layer over a period of 100 days up to passages 20 and the expression of alkaline phosphatase (AP), Oct-4, Nanog and Sox-2, GAPDH and ß-actin could be detected by RT-PCR. The cells exhibited uniform morphology and normal chromosome number. The up-regulation or down-regulation of transcription factors of each gene varied with passage number. We conclude that putative bubaline AF cells can be cultured and maintained in vitro for a prolonged period and offer a potential source of multipotent cells for applications including assisted reproduction in buffalo.