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.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

Coronectomy of mandibular third molars: a systematic literature review and case studies.

BACKGROUND: Extraction of mandibular third molars (M3M) close to the inferior alveolar nerve (IAN) has a higher risk of neurological disturbance. This review aims to evaluate the evidence supporting the use of the coronectomy technique compared to complete extraction for such M3Ms. Case studies by a specialist oral and maxillofacial surgeon are included to illustrate clinical practice. METHODS: Three databases (Cochrane Library, Embase, PubMed) were searched (November 2020). Additional articles were sought by hand searching the reference list of included articles. All studies published in English comparing outcomes of coronectomy with complete extraction with at least 50 subjects and 6 months follow-up were included. RESULTS: Of the six included studies, five reported a lower rate of IAN disturbance after coronectomy compared with complete extraction. There were no reported cases of lingual nerve disturbance. Other outcomes of coronectomy such as pain, infection, alveolar osteitis were either similar or lower compared to complete extraction. There were high rates of root migration but low rates of exposure and reoperation. Follow-up protocols varied considerably. CONCLUSIONS: There is medium quality evidence to support the option of coronectomy for high risk M3M cases. Further studies to develop follow-up protocols to assist general dental practice is warranted.

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.

Considerations for Pregnant Dental and Health Care Workers amid COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a highly contagious disease that quickly reached pandemic levels. Over 5 million COVID-19 cases and approximately 330,000 deaths have been recorded worldwide. Transmission is primarily spread through direct, indirect (through contaminated objects or surfaces), or close contact with infected people via respiratory droplets, the mouth, and/or nose secretions. Health care professionals (HCPs), including dental HCPs, are recognized to be at considerably high risk for infection due to the close proximity to patients and aerosol-generating procedures. During pregnancy, HCPs may be at even higher risk since pregnancy substantially increases the susceptibility to infectious diseases. OBJECTIVES: Here, we present the posed risks and potential effects of COVID-19 on maternal and fetal health. Current prevention and management strategies for COVID-19 on pregnant dental and HCPs are also discussed. RESULTS: Significant progress is being made in understanding the pathogenesis and clinical consequences of COVID-19. Pregnant women are affected more adversely with viral illnesses, although evidence of vertical transmission of COVID-19 is controversial. Based on the presence of atypical symptoms, the significant numbers of asymptomatic individuals who are COVID-19 positive, and the high susceptibility to viral diseases observed in pregnant women, recommendations have been put forth to limit the exposure of COVID-19-positive or even suspected cases to pregnant HCPs, and these are likely to evolve as new information becomes available. CONCLUSION: Pregnant HCPs require extra caution: not only are they considered a high-risk population, but their work at the frontline in a pandemic may expose them to additional risks. Complete awareness of the effects of COVID-19 on maternal and fetal/infant health, as well as prevention and management guidelines for pregnant HCPs, will allow for a safer work environment. Health care institutional policies aimed at protecting pregnant HCPs should consider avoiding their assignment as first responders, especially if equally trained staff are available. KNOWLEDGE TRANSFER STATEMENT: Dental and health care professionals can use the information in this review to improve their awareness of COVID-19 risks, signs, and symptoms and the associated effects on the health of pregnant health care professionals and their unborn/newborn children.

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.

Frequent attendance and the concordance between PHQ screening and GP assessment in the detection of common mental disorders.

OBJECTIVE: Frequent Attenders (FAs) have high rates of both common mental disorders (CMD) and physical disorders, partly justifying this service use behaviour. This study examines both case and non-case concordance between CMDs as estimated by a self-report screening questionnaire and as rated by the general practitioner (GP), in FAs compared to Other Attenders (OAs). METHODS: 2275 patients of an overlapping sample of 55 GPs from 2 surveys performed 10 years apart, completed in the waiting room the Patient Health Questionnaire (PHQ) and Client Service Receipt Inventory on 6-month service use. For each patient, the GP rated mental health on a 0-4 scale, with a clear indication that scores of 2 and above referred to caseness. PHQ-CMDs included major and other depressive, anxiety, panic, and somatoform disorders, identified using the original PHQ DSM-IV criteria-based algorithms. FA was defined as the top 10% of attenders in age, sex and survey-year stratified subgroups. RESULTS: FAs had higher rates of PHQ-CMDs (42% versus 23% for OAs, p < .0001). They reported more personal and social problems, disability and had higher GP-rated physical illness. Survey-day antidepressant/anxiolytic medication prescription was higher for FAs (p < .0001), with (p = .02) but also without a CMD (p < .0001). Both GP/PHQ case and non-case concordance differed between FAs and OAs, with a non-case concordance odds ratio of 0.5 (95% CI: 0.3-0.7, p = .001) for FAs compared to OAs. CONCLUSION: Despite a greater likelihood of GPs detecting CMDs in FAs, our findings suggest a potential risk of 'over-detection' of patients not reaching CMD threshold criteria among FAs.

[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.

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.

Multiple image x-radiography for functional lung imaging.

Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

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}.

Exact solution of cilia induced flow of a Jeffrey fluid in an inclined tube.

The present study investigated the cilia induced flow of MHD Jeffrey fluid through an inclined tube. This study is carried out under the assumptions of long wavelength and low Reynolds number approximations. Exact solutions for the velocity profile, pressure rise, pressure gradient, volume flow rate and stream function are obtained. Effects of pertinent physical parameters on the computational results are presented graphically.

Development and Validation of Written Exam Items for the Agricultural Hazardous Occupations Orders (AgHOs) Certification Training Program.

Research was conducted to develop and validate a pool of exam items that can be used to test the readiness of youth, ages 14-15 years, to be certified under the current federally mandated Agricultural Hazardous Occupations Orders (AgHOs). The AgHOs require training prior to employment in agricultural workplaces that the Secretary of Labor has determined are especially hazardous for youth within the prescribed age range. Under the current provisions of the AgHOs certification process, non-exempt youth seeking employment in agriculture are required to pass a written exam concentrating on safe work practices as partial satisfaction to receive certification of eligibility for employment to perform certain tasks. However, the regulations provide little guidance concerning the format of the exam, subject matter to be covered, degree of difficulty, or minimum passing score. As part of the USDA-sponsored Hazardous Occupations Safety Training in Agriculture (HOSTA) initiative, efforts have been made to develop consistent and evidence-based testing methods for disseminating the test protocols to instructors. The goal was to expand, enhance, and maintain the reliability of the exam item pool for the AgHOs certification process. Item development was based on the HOSTA-supported Gearing Up for Safety: Production Agriculture Safety Training for Youth curriculum. To ensure adequate item availability, the current item pool was expanded to include a minimum of two test items for each of the 157 cognitive-based core competencies developed as part of the Gearing Up curriculum design process. Administering 70-item exams that were generated from the item pool to 568 youth, ages 13-18 years, provided evidence of item validity. The result was a pool of 367 validated exam items.

From GWAS to function: lessons from blood cells.

Haematopoiesis, or the process of formation of mature blood cells from committed progenitors, represents an accessible and well-studied paradigm of cell differentiation and lineage specification. Genetic association studies provide a powerful approach to discover new genes, biological pathways and mechanisms underlying haematopoietic development. Here, we highlight recent findings of genomewide association studies (GWAS) linking 145 genomic loci to traits affecting the formation of red and white cells and platelets in European and other ancestries. We present strategies to address the main challenges in GWAS discoveries, particularly to find functional and regulatory effects of genetic variants, and to identify genes through which these genetic variants affect haematological phenotypes. We argue that studies of haematological trait variation provide an ideal paradigm for understanding the function of GWAS-associated variants owing to the accessible nature of cells, simple cellular phenotype and focused efforts to characterize the genetic and epigenetic factors influencing the regulatory landscape in highly pure mature cell populations.

Imaging transporters: Transforming diagnostic and therapeutic development.

Molecular imaging allows noninvasive assessment of drug distribution across pharmacological barriers. Thus, it plays an increasingly important role in efforts to understand the interactions of molecules with membrane transporters during drug development and in clinical pharmacology. We describe established and emerging imaging modalities utilized for studying transporter expression and function. We further present examples of how molecular imaging could provide insights into the contribution of transporters to drug disposition and effects.

Fetuin-A and vascular calcification in Indian end-stage renal disease population.

Fetuin-A levels, its correlation with vascular calcification and other biochemical markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) has not been studied in Indian end-stage renal disease population. Forty patients on dialysis for more than 3 months were studied. Biochemical parameters of CKD-MBD, highly sensitive-C reactive protein (hs-CRP), lipid profile and fetuin-A levels were estimated. Multi-slice computed tomography (MSCT) at the level of L1-L4 was done, and calcification score calculated using AJ 130 smart score. Levels of fetuin-A were correlated with calcification score and biochemical markers of CKD-MBD. Mean fetuin-A levels were 0.33 ± 0.098 g/l. Positive correlation of abdominal aortic calcification scores was found with age (P < 0.01) and duration of dialysis (P = 0.018). No correlation was detected between MSCT score, calcium phosphate product, intact parathyroid hormone, vitamin D, triglycerides and fetuin-A, and there was no correlation between fetuin-A levels, age, dialysis duration and calcium phosphate product but a significant correlations with vitamin D3 (P = 0.034), serum albumin (P = 0.002) was detected. Inverse correlation with hs-CRP was obtained. Patients with ischemic heart disease had numerically lower levels of fetuin-A (P = 0.427) and numerically higher MSCT score (P = 0.135). Patients with low hs-CRP (<10) had numerically higher fetuin-A levels (P = 0.090) and significantly low MSCT scores (P = 0.020). Calcium deposition seen on MSCT increases with age and duration of dialysis but is not related to fetuin-A levels. Inconclusive relationship exists with other parameters of CKD-MBD. Large controlled studies are needed to establish the role of fetuin-A in vascular calcification in Indian population.

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.