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Although studies show that organizations engaged in controversial actions often aim to minimize the release of threatening information, scholars know relatively little about what may prompt organizations to increase transparency in these situations. In this study, we focus on support from public opinion as a condition that may influence the disclosure of sensitive performance information to the public. Using the second Iraq War as an empirical context, we focus on the extent to which public officials—Pentagon spokespersons—release and frame information about war performance. This outcome is critical because the way in which organizations communicate their performance to outsiders has often been regarded as a key defensive impression management tactic. We hypothesize that high public support for the war will increase the likelihood that Pentagon officials release information about sensitive combat performance indicators in their press briefings and identify contingencies, such as adversity and organizational spokespersons’ power, that moderate this relationship. We also explore whether high public support decreases the strategic use of alternate performance frames that emphasize metrics that signal progress toward a desirable end state. Using a unique data set based on the coding of press briefings, public opinion data, and other public sources, we find support for several of our hypotheses. We discuss implications for understanding the relationship between public opinion and impression management and highlight the importance of extending this research to nongovernmental organizations. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2022.1598 .

Organizations often face challenges in incorporating the sustainable development goals (SDGs) into their strategic agendas. Despite the availability of guidelines from leading practitioners, such guidance often lacks the scientific insights provided by academia. In this study, we examine the integration of scholarly management literature into practical guidelines for achieving the SDGs. To do so, we first examined nine practitioner guidelines offered by well-reputed consulting firms, multilateral organizations and non-profits, from which we identified four underlying general processes: prioritizing SDGs to the most relevant strategic goals of firms, contextualizing the SDGs to firms’ geographical and industrial contexts, collaborating with other organizations and stakeholders to make more impactful progress and innovating via business process remodelling. Using these four processes as an overarching framework, we then conducted an interpretive literature review to mine highly cited sustainable development-related papers in the management field covering an 11-year period (2010–2020). From these studies, we derived novel connections to all four stages to offer a more robust and scientifically informed process-based framework for SDG adoption. We discuss multiple scholarly implications, including the importance of enhancing knowledge about the various phases of the SDG adoption model, developing research on understudied SDGs, and expanding theoretical and methodological approaches to SDG research. Additionally, we provide a more grounded SDG adoption model with significant practical implications.

Purpose of Review A gap exists between PrEP interest and PrEP uptake in key populations (KP) for HIV prevention that may be ascribed to PrEP delivery services not being acceptable. This review summarizes novel platforms for HIV prevention outside of the traditional health facilities environment. Recent Findings Mobile health clinics provide highly acceptable integrated, KP-focused services at convenient locations with the potential of high PrEP uptake. Telemedicine and health apps decongest health systems and allow for personal agency and informed decision-making on personal health. Pharmacy-led PrEP delivery provides de-medicalized, confidential PrEP services at extended hours in community locations, from trusted medical professionals. Peer-supported delivery encourages continued PrEP use. Summary Community-based, differentiated and de-medicalized PrEP delivery can address uptake and continued use barriers in key populations. Future research should assess scalability, cost-effectiveness and sustainability of these PrEP delivery platforms, as well as focus on ways to simplify PrEP provision.

Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

The Aedes aegypti mosquito transmits both dengue virus (DENV) and Zika virus (ZIKV) . Individuals in endemic areas are at risk for infection with both viruses, as well as for repeated DENV infection. In the presence of anti-DENV antibodies, outcomes of secondary DENV infection range from mild to life threatening. Furthermore, the role of cross-reactive antibodies on the course of ZIKV infection remains unclear. We assessed the ability of cross-reactive DENV mAbs or polyclonal immunoglobulin isolated after DENV vaccination to upregulate type I IFN production by plasmacytoid DCs (pDCs) in response to both heterotypic DENV- and ZIKV-infected cells. We found a range in the ability of antibodies to increase pDC IFN production and a positive correlation between IFN production and the ability of an antibody to bind to the infected cell surface. Engagement of Fc receptors on the pDC and engagement of epitope on the infected cell by the Fab portion of the same antibody molecule was required to mediate increased IFN production by providing specificity to and promoting pDC sensing of DENV or ZIKV. This represents a mechanism independent of neutralization by which preexisting cross-reactive DENV antibodies could protect a subset of individuals from severe outcomes during secondary heterotypic DENV or ZIKV infection.

HIV-1 infection persists in humans despite expression of antiviral type 1 interferons (IFN). Even exogenous administration of IFNα only marginally reduces HIV-1 abundance, raising the hypothesis that people living with HIV-1 (PLWH) are refractory to type 1 IFN. We demonstrated type 1 IFN refractoriness in CD4(+) and CD8(+) T cells isolated from HIV-1-infected persons by detecting diminished STAT1 phosphorylation (pSTAT1) and interferon-stimulated gene (ISG) induction upon type 1 IFN stimulation compared to those in cells from healthy controls. Importantly, HIV-1-infected people who were virologically suppressed with antiretrovirals also showed type 1 IFN refractoriness. We found that USP18 levels were elevated in people with refractory pSTAT1 and ISG induction and confirmed this finding ex vivo in CD4(+) T cells from another cohort of HIV-hepatitis C virus (HCV) coinfected persons who received exogenous pegylated interferon-α2b in a clinical trial. We used a cell culture model to recapitulate type 1 IFN refractoriness in uninfected CD4(+) T cells that were conditioned with media from HIV-1 inoculated peripheral blood mononuclear cells (PBMCs), inhibiting de novo infection with antiretroviral agents. In this model, RNA interference against USP18 partly restored type 1 IFN responses in CD4(+) T cells. We found evidence of type 1 IFN refractoriness in PLWH irrespective of virologic suppression that was associated with upregulated USP18, a process that might be therapeutically targeted to improve endogenous control of infection. IMPORTANCE People living with HIV-1 (PLWH) have elevated constitutive expression of type 1 interferons (IFN). However, it is unclear whether this affects downstream innate immune responses. We identified refractory responses to type 1 IFN stimulation in T cells from PLWH, independent of antiretroviral treatment. Type 1 IFN refractoriness was linked to elevated USP18 levels in the same cells. Moreover, we found that USP18 levels predicted the anti-HIV-1 effect of type 1 IFN-based therapy on PLWH. In vitro, we demonstrated that refractory type 1 IFN responses were transferrable to HIV-1-uninfected target CD4(+) T cells, and this phenomenon was mediated by type 1 IFN from HIV-1-infected cells. Type 1 IFN responses were partially restored by USP18 knockdown. Our findings illuminate a new mechanism by which HIV-1 contributes to innate immune dysfunction in PLWH through the continuous production of type 1 IFN that induces a refractory state of responsiveness.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1–2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, −53%; 95% CI, −255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, −66%; 95% CI, −250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10(3) IU per milliliter and 1804.93×10(3) IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.)

The aim of the study was to evaluate the outcomes of prophylactic thyroidectomies performed in an academic setting in the context of multiple endocrine neoplasia type 2 (MEN2) syndrome.A chart review of patients18years old who underwent prophylactic thyroidectomy for a MEN2 syndrome at a children's hospital between 2006 and 2015 was performed.The study included 21 patients (57% female) with a mean age of 6.2±2.5years. All patients were asymptomatic at first evaluation. Nineteen had MEN2A syndrome with RET proto-oncogene mutations identified. The remaining two were RET-negative with familial medullary thyroid cancer (FMTC). One patient had a concomitant Hirschsprung disease. Of the 11 patients who had RET proto-oncogene mutations ranked as Moderate Risk for medullary thyroid cancer (MTC) (American Thyroid Association), one had a microcarcinoma on the resected specimen, and the others had C-Cell Hyperplasia. Among the 8 patients who had RET proto-oncogene mutations ranked as High Risk level for MTC, all had microcarcinoma. Of the nine patients with microcarcinoma, three underwent surgery after 5years of age. No microcarcinoma exceeded 6mm. There were no permanent complications. Six patients experienced transient hypocalcemia, of which only one was symptomatic. No patients had lymph node involvement, and no recurrence was noted during the follow-up period.Of 21 children with familial thyroid cancer syndrome who underwent a prophylactic thyroidectomy, nine had microcarcinoma. This study highlights the need for a complete familial history, including FMTC history and mandatory preventive surgical approach.III.

To evaluate the functional and anatomic recovery of submacular hemorrhage (SMH), treated with vitrectomy, subretinal injection of rtPA and gas tamponade, to highlight the risk factors for their occurrence as well as the factors influencing prognosis.This is a single-center retrospective study. Thirty-two eyes of 30 patients from the Clermont-Ferrand University Hospital were included, with a submacular hemorrhage (SMH) requiring surgical evacuation. The primary endpoint was final postoperative visual recovery. Visual acuities (AV) were converted to the logarithmic minimum angle of resolution scale (logMAR) for statistical analysis.The average time from onset of symptoms to surgery was 4.8±3.3 days. The initial VA was 2.1±0.3 logMAR, with an average improvement of 0.7±0.7 logMAR (P=0.0004) at the final visit. The mean thickness of the SMH decreased by 729±352μm (P0.0001) at the final visit.Treatment of SMH with vitrectomy, subretinal injection of rtPA and gas tamponade results in a statistically significant improvement in final VA, as well as a significant decrease in SMH thickness on OCT.

Aim of the study Recent publications suggest pediatric surgeons may not be well suited to perform thyroid surgeries unless considered high volume. We sought to assess the outcome of thyroidectomies performed by pediatric surgeons in an academic setting. Methods We reviewed charts of patients younger than 18 years who underwent thyroid surgeries at a free standing children's hospital between April 2006 and October 2015. Main results The analysis included 118 surgeries in 98 patients (mean age 11.8 years). Most surgeries were performed by a single pediatric surgeon (average 10 thyroidectomies per year). The commonest indication for resection was thyroid nodule (64%). 80% of patients had a single surgery; the remainder had two, including 13 completion hemithyroidectomies. Cancer was found in 37% of specimens, with papillary subtype being most common (72%). Seven patients had locoregional metastases and one had pulmonary metastases. Among the 17 malignant cases that had a second intervention, 6 had malignancy in the resected specimen. There were no deaths in the follow up period (mean 2.7 years). Two patients had permanent hypocalcemia, and three had persistent unilateral recurrent laryngeal nerve injuries causing dysphonia for a total permanent complication rate of 4.2%. Conclusions We conclude that pediatric thyroidectomy is a safe procedure when performed by pediatric surgeons. Our rate of complications is comparable to those reported in the literature. Our data highlight the need for a vigilant and multidisciplinary approach for children with thyroid pathology. Type of study Treatment study. Level of evidence IV.

Resume Introduction L’atteinte oculaire par Candida albicans est rare et peut se manifester sous forme d’endophtalmie endogene ou de choroidite. Elle fait suite a une septicemie a C. Albicans , rencontree en contexte de reanimation ou de toxicomanie intraveineuse. Nous rapportons deux cas suivis dans notre service presentant des caracteristiques, un terrain, un mode diagnostique et une evolution differents. Observations Il s’agissait d’une femme âgee de 37 ans, aux antecedents de toxicomanie intraveineuse, presentant une endophtalmie a C. albicans . Une bitherapie antifongique intraveineuse etait instauree mais une vitrectomie et une injection intravitreenne d’amphotericine B etaient realisees du fait d’une aggravation de l’endophtalmie. Le deuxieme cas concernait un homme de 53 ans, hospitalise en reanimation depuis 1 mois pour septicemie a C. Albicans presentant un foyer chorioretinien maculaire gauche. Un traitement antifongique intraveineux etait instaure et permettait la regression du foyer. Discussion Nos cas illustrent les deux modalites d’atteinte ophtalmologique de la candidose necessitant des traitements differents bien codifies par des recommandations : dans le cas de l’endophtalmie le recours a une vitrectomie couplee a une injection intravitreenne parallelement a un traitement antifongique intraveineux est souvent necessaire alors que dans le cas du foyer choroidien, le traitement antifongique parenteral est souvent suffisant. Conclusion Le depistage precoce, l’instauration du traitement et du suivi ophtalmologique sont difficiles mais necessaires chez ces populations en rupture de soins ou en reanimation. La prise en charge de ces candidoses repose sur une bonne collaboration entre l’ophtalmologue et le reanimateur ou l’infectiologue.

The propagation of stress waves in epoxy–glass particulate composites and graded materials was studied experimentally. Materials tested in this study consisted of an epoxy matrix with various concentrations of spherical glass particles having a mean diameter of 42 μm. Plate impact experiments were performed using a gas gun. Embedded within the specimens were manganin stress gauges used to record propagating compressive longitudinal stress waves through the material. High strain rate experiments using a Split Hopkinson Pressure Bar (SHPB) apparatus were also performed to evaluate the dynamic strength of the specimens, while quasi-static compression tests were undertaken to characterize their quasi-static behavior. Ultrasonic wave speed measurements were carried-out in order to obtain additional material properties and characterize the gradation in functionally graded materials (FGM). It was found that low volume fractions of particles are detrimental to the performance of the material under impact loading, while concentrations in the range of about 30 to 45% by volume exhibit characteristics of higher degrees of scattering. This suggests that materials in this latter range would be more effective in the thwarting of destructive shock waves than the homogeneous matrix material. Impact testing of FGM specimens suggests that impact loading on the stiff (high volume fraction) face results in much higher levels of scattering. Therefore, such materials would be effective for use in light weight armor or as shielding materials due to their effective attenuation of mechanical impulses.

OBJECTIVES The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer. METHODS This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergonie Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis. RESULTS The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific. CONCLUSION Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.

© 2017 Hopp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Proteases have been implicated in a variety of developmental processes during the malaria parasite lifecycle. In particular, invasion and egress of the parasite from the infected hepatocyte and erythrocyte, critically depend on protease activity. Although falcipain-1 was the first cysteine protease to be characterized in P. falciparum, its role in the lifecycle of the parasite has been the subject of some controversy. While an inhibitor of falcipain-1 blocked erythrocyte invasion by merozoites, two independent studies showed that falcipain-1 disruption did not affect growth of blood stage parasites. To shed light on the role of this protease over the entire Plasmodium lifecycle, we disrupted berghepain-1, its ortholog in the rodent parasite P. berghei. We found that this mutant parasite displays a pronounced delay in blood stage infection after inoculation of sporozoites. Experiments designed to pinpoint the defect of berghepain-1 knockout parasites found that it was not due to alterations in gliding motility, hepatocyte invasion or liver stage development and that injection of berghepain-1 knockout merosomes replicated the phenotype of delayed blood stage growth after sporozoite inoculation. We identified an additional role for berghepain-1 in preparing blood stage merozoites for infection of erythrocytes and observed that berghepain-1 knockout parasites exhibit a reticulocyte restriction, suggesting that berghepain-1 activity broadens the erythrocyte repertoire of the parasite. The lack of berghepain-1 expression resulted in a greater reduction in erythrocyte infectivity in hepatocyte-derived merozoites than it did in erythrocyte-derived merozoites. These observations indicate a role for berghepain-1 in processing ligands important for merozoite infectivity and provide evidence supporting the notion that hepatic and erythrocytic merozoites, though structurally similar, are not identical., This work was supported by the National Institutes of Health (R01 grant A1056840 to PS), a Johns Hopkins Malaria Research Institute fellowship (CSH) (malaria.jhsph.edu/opportunities/fellowships/) and the Netherlands Organization for Scientific Research Rubicon fellowship (WAvdL) (www.nwo.nl/funding-rubicon).

Resume Nous rapportons le cas d’un patient masculin de 43 ans se presentant a la consultation de neuro-ophtalmologie et uveites du CHU de Clermont-Ferrand pour une baisse d’acuite visuelle de l’œil droit. Deux mois plus tot, le patient avait presente une baisse d’audition gauche non etiquetee. Le fond d’œil et l’angiographie retrouvent un aspect de vascularite avec un aspect de plaque choroidienne, ainsi qu’une papillite. La serologie TPHA-VDRL est positive dans le sang et le liquide cephalorachidien. Mais le bilan de medecine interne retrouve de nombreuses anomalies associees : hyperhomocysteinemie, anticorps anticardiolipides positifs, anticorps anti-β2GP1 positifs, allongement du TCA non corrige par l’adjonction de plasma temoin, presence d’un anticorps a activite antiprothrombinase, test de resistance a la proteine C activee positif. Sur le plan ORL, il existe un syndrome vestibulaire gauche harmonieux, l’audiogramme montre une surdite de perception de −40 dB. Le patient recoit un traitement de neurosyphilis permettant la disparition de la vascularite, la plaque choroidienne et de la papillite. Sur le plan ORL, le syndrome vestibulaire a regresse et l’areflexie vestibulaire a disparu. L’audiogramme s’ameliore avec la persistance d’une hypoacousie gauche de l’ordre de −20 dB. Les anomalies immunologiques ont elles aussi disparues. Notre cas illustre le polymorphisme de presentation de la syphilis et ses possibilites d’association avec une surdite de perception ainsi que des anomalies immunologiques.

Immunoglobulin G4-related sclerosing disease (IgG4-SD), also referred to as IgG4-related disease, is a newly described disease characterized by an infiltration of IgG4+ plasma cells in the early stages of the affection of an organ. Well documented in the pancreas and then detected in other organs, only few cases of thyroid affection have been reported. In addition, no case of IgG4-SD of the thyroid associated with high serum IgG4 levels has ever been described. We report here the first case.

Riedel's thyroiditis appears in the form of a hard cervical mass with rapid onset, and it is associated with extensive fibrosis that compresses nearby structures, such as the trachea and supra-aortic vessels; its diagnosis is essentially histopathological. Although its histological characteristics have been well established, there are some diagnostic pitfalls. We report here the case of a 37-year-old woman, with clinical and histopathological data suggesting Riedel's disease. Fibrosis regressed after treatment with corticosteroids, relieving the compressed airways. However, in contrast with the latest knowledge on this disease, the IgG4 serum levels were consistently normal, and positron emission tomography in search of extensive fibrosis revealed an abnormal metabolic activity of the bone marrow. The final diagnosis revised by the histopathologist was that of nodular sclerosing Hodgkin's lymphoma. This case allows us to review the diagnostic approach when facing a thyroid mass with extremely rapid evolution.

The effects of impact loading on changes in microstructure have been studied in low carbon steel. Low to moderate shock loading tests have been carried out on steel specimens using a single stage gas gun with projectile velocities ranging from 200 to 500 m/s. Stress history at the back face of the target specimen and projectile velocity prior to impact were recorded via manganin stress gauges and velocity lasers, respectively. A Johnson–Cook constitutive material model was employed to numerically simulate the material behavior of low carbon steel during impact and obtain the particle velocity at the impact surface as well the pressure distribution across the specimens as a function of impact duration. An analytical approach was used to determine the twin volume fraction as a function of blast loading. The amount of twinning within the α-ferrite phase was measured in post-impact specimens. A comparison between experimental and numerical stress histories, and analytical and experimental twin volume fraction were used to optimize the material and deformation models and establish a correlation between impact pressure and deformation response of the steel under examination. Strain rate controlled tensile tests were carried out on post-impact specimens. Results of these tests are discussed in relation to the effects of impact loading on the yield and ultimate tensile strength as well as the hardening and strain energy characteristics.

We have synthesized 20-hydroxyeicosatetraenoic acid (20-HETE) following a new route and delineated its functional effects in human bronchi. Isometric tension measurements were performed, and they demonstrated that synthetic 20-HETE induced a concentration-dependent relaxant effect in ASM on resting tone and on bronchi pre-contracted with methacholine.

BACKGROUND: Unintentional injuries are the leading cause of mortality and morbidity in children and teenagers in Canada. Few publications have addressed injuries caused by jewellery and ornaments in children. OBJECTIVES: To examine the mechanisms and the incidence of injuries caused by jewellery and ornaments in children and teenagers, to identify children at high risk for these type of injuries and to recommend specific injury prevention strategies. METHODS: Data were analyzed from a Canadian database (Canadian Hospitals Injury Reporting and Prevention Program) of a tertiary paediatric centre. All patients between zero and 18 years of age who were diagnosed in the emergency department with jewellery- and ornament-related injuries during a 10-year period (1997 to 2006) were identified. Patients were categorized according to six age groups (younger than one year of age; one to two years of age; two to four years of age; five to nine years of age; 10 to 14 years of age, and 15 to 18 years of age). For each case, the context and the mechanism of injury were investigated. RESULTS: From a total of 150,771 reported injury cases, 380 (0.25%) were jewellery related. Unlike with most trauma, girls predominate in this kind of injury (n=288; 75.8% of cases). Over one-half of cases (58.1%) were reported for children four years of age or younger. Emergency physicians reported the presence of jewellery as a foreign body in a natural orifice (mouth, nose, ear or genitourinary tract) in 308 cases (81%). No case of intestinal obstruction, strangulation or death was reported. Eleven cases (2.9%) required emergency hospitalization, all for endoscopic evaluation of a foreign body in the airway or in the digestive tract. In the adolescent group, five cases of injuries secondary to piercing were reported. CONCLUSION: The present study demonstrates that, although jewellery-related injuries are relatively infrequent, some can cause severe injuries that could compromise patients' health. As a primary prevention strategy, doctors and health professionals working with children should make parents and caregivers aware of the possibility of trauma in children wearing or playing with jewellery, especially in the zero- to four-year-old group requiring closer supervision. Specific anticipatory guidance concerning piercing may be helpful to adolescents. Language: en

Organophosphate resistant and susceptible tick larvae from laboratory strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus were exposed to low doses of the organophosphate (OP) acaricide, coumaphos. Serial analysis of gene expression (SAGE) was used to analyse differential gene expression in response to OP treatment and to compare the responses of OP-treated and -untreated resistant and susceptible tick larvae. An R. microplus Gene Index was used as an EST database to identify genes which corresponded to SAGE tags whose abundance changed in response to acaricide exposure. Relative quantitative RT-PCR was used to confirm the differential expression results from the SAGE experiments. Of particular interest is a SAGE tag which corresponds to a cytochrome P450-like EST in the Gene Index which was more abundant in untreated OP resistant larvae compared to untreated OP susceptible larvae. This SAGE tag was also more abundant in OP resistant larvae treated with OP compared to OP susceptible larvae treated with OP.

The embryotoxicity of co-planar PCBs is regulated by the aryl hydrocarbon receptor (Ahr), and has been reported to involve oxidative stress. Ahr participates in crosstalk with another transcription factor, Nfe2l2, or Nrf2. Nrf2 binds to antioxidant response elements to regulate the adaptive response to oxidative stress. To explore aspects of the crosstalk between Nrf2 and Ahr and its impact on development, we used zebrafish (Danio rerio) with a mutated DNA binding domain in Nrf2a (nrf2afh318/fh318), rendering these embryos more sensitive to oxidative stress. Embryos were exposed to 2 nM or 5 nM PCB126 at 24 hours post fertilization (prim-5 stage of pharyngula) and examined for gene expression and morphology at 4 days post fertilization (dpf; protruding –mouth stage). Nrf2a mutant eleutheroembryos were more sensitive to PCB126 toxicity at 4 dpf, and in the absence of treatment also displayed some subtle developmental differences from wildtype embryos, including delayed inflation of the swim bladder and smaller yolk sacs. We used qPCR to measure changes in expression of the nrf gene family, keap1a, keap1b, the ahr gene family, and known target genes. cyp1a induction by PCB126 was enhanced in the Nrf2a mutants (156-fold in wildtypes vs. 228-fold in mutants exposed to 5 nM). Decreased expression of heme oxygenase (decycling) 1 (hmox1) in the Nrf2a mutants was accompanied by increased nrf2b expression. Target genes of Nrf2a and AhR2, NAD(P)H:quinone oxidoreductase 1 (nqo1) and glutathione S-transferase, alpha-like (gsta1), showed a 2-5-fold increase in expression in the Nrf2a mutants as compared to wildtype. This study elucidates the interaction between two important transcription factor pathways in the developmental toxicity of co-planar PCBs.

Exposures to co-planar PCBs and dioxins have been associated with diabetes in epidemiologic studies. Individuals may be predisposed to diseases such as diabetes as a result of exposure to environmental contaminants during early life, resulting in dysmorphic pancreatic islets or metabolically fragile β-cells. We tested the hypothesis that embryonic exposure to a model Ahr-ligand, PCB-126 would cause structural and/or functional alterations to the developing primary pancreatic islet in the zebrafish (Danio rerio). To assess β-cell development, transgenic zebrafish embryos (Tg(ins:GFP) and Tg(ins:mcherry) were exposed to nominal concentrations of 2 or 5nM PCB-126 or DMSO from 24-48h post fertilization (hpf), and imaged via time-lapse microscopy from 80-102hpf. We identified defects including hypomorphic islets, altered islet migration, islet fragmentation, and formation of ectopic β-cells. As we recently showed the transcription factor Nrf2a is protective in PCB-126 embryotoxicity, we then assessed the transcriptional function of the islets in wildtype and nrf2a(fh318/fh318) mutant embryos. We measured gene expression of preproinsulin a, somatostatin2, pdx1, ghrelin, and glucagon. Expression of preproinsulin a increased with PCB treatment in wildtype embryos, while expression of all measured pancreas genes was altered by the nrf2a mutant genotype, suggesting misregulation of the glucose homeostasis axis in those embryos, independent of PCB treatment. This study shows that embryonic exposure to PCB-126 can result in deviant development of the pancreatic islet and suggests that Nrf2a plays a role in regulating glucose homeostasis during development.

Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25±3 kg/m2) and 19 obese (BMI 55± 8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity.

Immunoglobulin G4-related sclerosing disease (IgG4-RSD) represents a recently identified inflammatory disorder in which infiltration of IgG4 plasma cells causes fibrosis in organs. While IgG4-RSD is well documented in the pancreas and other organs, it is poorly characterized in the thyroid gland. We report a case of a 48-year-old female with a fibrotic thyroid mass associated with a retroperitoneal fibrosis. Diagnosed early as Riedel disease, the high serum IgG4, immunohistopathology and decreased fibrosis with corticosteroid therapy, finally confirm for the first time, the origin of IgG4-RSD fibrosis of the thyroid.

The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer.This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergonié Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis.The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific.Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical.

Ocular involvement by Candida albicans is rare and may present as endogenous endophthalmitis or choroiditis. It occurs in the context of C. albicans septicemia, in the context of intensive care unit hospitalization or intravenous drug use. We report two cases referred to our department with different characteristics, background, diagnostic modalities and different courses.A 37-year-old woman, with a history of intravenous drug use, presented with C. albicans endophthalmitis. Intravenous combination antifungal therapy was begun, but vitrectomy and intravitreal amphotericin B were performed due to worsening of the endophthalmitis. The second case was a 53-year-old man who was hospitalized in the intensive care unit for C. albicans septicemia with a left macular chorioretinitis. Intravenous antifungal therapy was initiated and allowed regression of the ocular lesion.Our cases illustrate both types of ophthalmic involvement by candidiasis requiring different treatments with well-described recommendations: in the case of endophthalmitis, the use of vitrectomy and intravitreal amphotericin B injection in association with intravenous antifungal treatment, whereas parenteral antifungal treatment is often sufficient in the case of chorioretinitis.Early detection, initiation of treatment and ophthalmologic monitoring are difficult but necessary in these populations non-compliant with follow-up or in intensive care units. The management of ocular candidiasis requires good collaboration between the ophthalmology, infectious diseases and intensive care unit departments.

Silver halide particles were synthesized in a water-in-oil microemulsion consisting of AOT (sodium bis 2-ethylhexylsulfosuccinate)/n-heptane/water. The study of the interaction of an oxa- and a thiacarbocyanine with the particles suggested that only the thiacarbocyanine was adsorbed. To determine the site of adsorption of the thiacarbocyanine, the influence of the particle charge on the adsorption was investigated. The adsorption of the 1,1‘-sulfopropyl-5,5‘-dichloro-9-ethyl thiacarbocyanine occurs by the interaction between the ring sulfur atom and the silver ion in the case of silver bromide and by the interaction between the nitrogen atom and the chloride ion in the case of silver chloride. NMR experiments have shown the adsorption of water and methanol molecules on the particles. Finally, stationary and time-resolved fluorescence measurements indicate a quenching effect of the dye fluorescence by the particles, suggesting that the dye molecules could be suitable for the spectral sensitization.

A phase I clinical trial is being currently performed in our institution, aiming at evaluating the feasibility and toxicity related to the administration of Herpes Simplex-thymidine kinase gene-expressing human primary T lymphocytes following allogeneic hematopoietic stem cell transplantation. The need for safe and standardized preparation conditions for gene-modified cells is crucial. We describe the closed culture system used in the current trial for ex vivo retroviral-mediated gene transfer and transduced cell selection. Cell handling is performed in closed systems using sampling and transfer pack bags, culture bags and a sterile connection device which avoids opening the culture system. This closed system allows safe and reproducible ex vivo preparation of gene-modified primary T-lymphocytes for clinical use.

Aims To describe a new technique of axillary dissection and evaluate the results. Methods Axillary lymphadenectomy prepared by fat and lymph node suction was performed on 43 patients with breast cancer and uninvolved axilla on physical examination. The mean follow-up was 18 months (range 12–27). After lipolysis and liposuction of the axilla, lymph node dissection was performed by axilloscopy in patients treated with conservative surgery. For patients undergoing modified radical mastectomy, a mastectomy with open axillary dissection was carried out. The axillary space was drained until less than 20 ml of lymphorrhea was being produced per day. Seventeen modified radical mastectomies (group M) and 26 lumpectomies (group L) were performed. Results No injury of muscles, vessels or nerves was observed. An average of 13.6 lymph nodes (8–31) were removed. In group L, the mean number of lymph nodes removed by liposuction, axilloscopy and control incision was 2.5, 5.4 and 4.2, respectively. In group M, the mean number of lymph nodes removed was 14. None of the 589 lymph nodes examined showed any pathological trauma. Fourteen patients (32%) had more than one histologically positive node. The mean quantity of lymphorrhea was 390 ml in group M and 275 ml in group L. The mean duration of drainage was 6 days in group M and 5 days in group L. Four patients had seromas which required punctures. Two patients had shoulder restriction (movements Conclusions Axillary lymphadenectomy prepared by fat and lymph node suction is a reliable and effective procedure. However, it does not appear to be better than standard dissection as regards post-operative complications, except for arm oedema, but this must be confirmed by further studies.

In 1993, the University of Montreal Medical School changed from an old teaching curriculum to a new one with Problem-Based-Learning as its major component. The first group of problems covers growth and development at all ages. The authors present this new learning method and discuss their experience and that of students with problems involving physiologic, psychologic and environmental learning objectives.

Numerical simulations of the parametric difference-frequency-mixing process in the femtosecond regime are presented. The calculations indicate that sub- 100 fs pulses may be produced in the 3 to 5 μm range using available sources. Theoretical results are compared to experiments on asynchronous frequency-mixing of two femtosecond Ti:sapphire lasers.

We report the case of a 43-year-old male patient presenting for neuro-ophthalmologic and uveitis consultation at Clermont-Ferrand University Medical Center for a reduction in visual acuity in his right eye. Two months previously, the patient had complained of decreased hearing on the left, which remained undiagnosed. Fundus examination and fluorescein angiogram showed the appearance of vasculitis with papillitis and a choroidal plaque. TPHA-VDRL serology was positive in blood and cerebrospinal fluid. Internal medicine work-up revealed many associated abnormalities: hyperhomocysteinemia, positive anticardiolipin antibody, positive anti-β2GP1 antibodies, increased partial thromboplastin time not corrected by the addition of control plasma, presence of an anti-prothrombinase antibody, positive activated protein C resistance. ENT examination showed a left harmonic vestibular syndrome; audiography showed a sensorineural hearing loss of -40 dB. The patient received treatment for neurosyphilis, which led to the disappearance of the vasculitis, the choroidal plaque and the papillitis. From an ENT standpoint, the vestibular syndrome and the left vestibular areflexia resolved. The audiogram improved, with persistence of left hearing loss (about -20 dB) with useful speech intelligibility. Immunologic abnormalities had also disappeared. Our case illustrates the protean presentations of syphilis and its possible association with sensorineural deafness and immunological abnormalities.

Twenty-four hourly urinary growth hormone excretion (24-h uGH) has been quantified using a combination of ultrafiltration and conventional immunoradiometric assay. Twenty-four hourly uGH was measured in 20 normal adults and in 42 patients with acromegaly (9 untreated, 28 treated but with above-normal IGF-I levels, and 5 treated and cured). The means and ranges were as follows: 3.7 (1–9) ng/24 h for normals and 160(40–540), 66(2–380) and 5.2 (4–8) ng/24 h for the three groups of acromegalic patients, respectively. Ten patients with pituitary adenomas without acromegaly had 24-h uGH within the normal range. Twenty-four hourly uGH therefore gives a clear differentiation between controls and untreated patients. Log-transformed values for subjects with acromegaly showed significant correlations between 24-h uGH and levels of IGF-I (r=0.63, p

Human herpesvirus 6 is a ubiquitous Herpesviridae infecting patients during childhood. Its role in ocular disorders is mostly unknown. We report the case of a 47-year-old woman with a history of rheumatoid arthritis (treated with etanercept) and tuberculosis, who presented with sudden unilateral panuveitis. The patient was initially treated with ganciclovir, as the polymerase chain reaction in the aqueous humor was positive for HHV6, and with pyrimethamine and sulfadiazine because a toxoplasmic co-infection was highly suspected, which was biologically confirmed. Management of HHV6 in a nervous system disorder is challenging because its replication has been proved but its role remains unclear. HHV6 may be pathogenic by itself but can facilitate co-infection as can etanercept.

Purpose Infantile hemangiomas of the orbit and eyelid can cause serious ocular problems, such as astigmatism and amblyopia. Magnetic resonance imaging and ultrasonography are the best ways to establish the diagnosis and to evaluate the extent of the lesion. Our goal was to correlate the lesion location with the visual impairment. Material and methods This was a retrospective study (1992-2004) of 63 cases of orbit and eyelid hemangiomas (13 male, 50 female patients; ages: 1 day old to 3 years old). Imaging methods were magnetic resonance imaging or computed tomographic-scanning and color Doppler ultrasonography. The anatomic definition was palpebral, extraconal, and extraconal with intraconal involvement. All patients had ophthalmologic evaluations. Results The hemangiomas were palpebral (n = 32) (normal vision: 19; amblyopia and/or astigmatism: 13), extraconal, and extraconal with intraconal involvement (n = 31) (normal vision: 4; amblyopia and/or astigmatism: 27). Limitations This study was small; a prospective study is needed. Conclusion Orbit and eyelid hemangiomas need to be carefully evaluated by an ophthalmologist. Extraconal and intraconal hemangiomas are more frequently associated with ocular involvement. However, ocular complications can occur in palpebral lesions.

Cancer vaccines are examples of active immunotherapy. In pediatric malignancy such active strategies may be particularly problematic because of immune suppression produced by the tumor or its intensive treatment with combined chemotherapy. Nonetheless, the expression of tumor- specific and tumor-associated antigens on a range of pediatric tumors has encouraged investigation of the approach in patients with either bulky or minimal residual disease. Here we describe promising results in neuroblastoma and acute leukemia, suing genetically modified whole cell vaccines, peptides, and dendritic cells. The difficulties of conducting and evaluating such studies in a pediatric population are also described, and a strategy for cancer vaccine development is outlined.

The in vivo disposition and antitumor efficacy of a newly developed phosphinic matrix metalloproteinase inhibitor (RXP03) were examined. RXP03 potently inhibits MMP-11, MMP-8 and MMP-13, but not MMP-1 and MMP-7. Twenty-four hours after i.p. injection into mice, most of the RXP03 was recovered intact in plasma, feces (biliary excretion) and tumor tissue. Pharmacokinetic parameters indicated that, after an i.p. dose of 100 mug/day, the plasma concentration of RXP03 over 24 hr remained higher than the Ki values determined for MMP-11, MMP-8 and MMP-13. Efficacy of RXP03 on the growth of primary tumors induced by s.c. injection of C-26 colon carcinoma cells in mice was observed to depend both on RXP03 doses and treatment schedules. Tumor volumes in mice treated for 18 days with 50, 100 and 150 mug/day of RXP03 were decreased compared with control tumor volumes, 100 mug/day being the most effective dose. Treatment at higher dose (600 mug/day) did not significantly reduce the tumor size as compared to control. Short treatments with RXP03 100 mug/day, 3 to 7 days after C-26 inoculation, were more effective on tumor growth than continuous treatment over 18 days. Strikingly, RXP03 treatment started 6 days after the C-26 injection and continued until day 18 led to stimulation of tumor growth, as compared to control. These paradoxical effects, depending on the RXP03 treatment schedule, underline the need to define carefully the spatiotemporal function of each MMP at various stages of tumor growth to achieve optimal therapeutic effects by MMP inhibitor treatment.

Aims/hypothesis: The specific contributions made by the various cell types in adipose tissue to obesity, particularly obesity-related inflammation, need to be clar- ified. The aim of this study was to elucidate the potential role of adipocyte precursor cells (preadipocytes/stromal vascular cells (SVC)). Methods: We performed Affyme- trix oligonucleotide microarray expression profiling of cul- tured abdominal subcutaneous preadipocytes/SVC isolated from the adipose tissue of 14 non-obese (BMI 25±4 kg/m 2 ) and 14 obese (55±8 kg/m 2 ) non-diabetic Pima Indian sub- jects. Quantitative real-time PCR (RT-PCR) was used to verify the differential expression of several genes in an independent group of subjects. Results: We identified 218 differentially expressed genes with p values less than 0.01. Microarray expression profiling revealed that the expression of inflammation-related genes was significant- ly upregulated in preadipocytes/SVC of obese individ- uals. Quantitative RT-PCR confirmed the upregulation of IL8, CTSS, ITGB2, HLA-DRA, CD53, PLA2G7 and MMP9 in preadipocytes/SVC of obese subjects. Conclusions/ interpretation: The upregulation of inflammation-related genes in preadipocytes/SVC of obese subjects may in- crease the recruitment of immune cells into adipose tissue and may also result in changes in the extracellular matrix (tissue remodelling) to accommodate adipose tissue expan- sion in obesity.

We used an expressed sequence tag approach to initiate a study of the genome of the southern cattle tick, Boophilus microplus. A normalized cDNA library was synthesized from pooled RNA purified from tick larvae which had been subjected to different treatments, including acaricide exposure, heat shock, cold shock, host odor, and infection with Babesia bovis. For the acaricide exposure experiments, we used several strains of ticks, which varied in their levels of susceptibility to pyrethroid, organophosphate and amitraz. We also included RNA purified from samples of eggs, nymphs and adult ticks and dissected tick organs. Plasmid DNA was prepared from 11,520 cDNA clones and both 5' and 3' sequencing performed on each clone. The sequence data was used to search public protein databases and a B. microplus gene index was constructed, consisting of 8270 unique sequences whose associated putative functional assignments, when available, can be viewed at the TIGR website (http://www.tigr.org/tdb/tgi). A number of novel sequences were identified which possessed significant sequence similarity to genes, which might be involved in resistance to acaricides.

Ependymal tumours are histologically and clinically varied lesions. Numerical abnormalities of chromosome 9 are frequently associated with these tumours. Nevertheless, the three important tumour suppressor genes located in this chromosome, CDKN2A, CDKN2B and p14 ARF, have not been reported to be commonly altered in them. We studied promoter methylation of these genes, an important mechanism associated with gene silencing in a series of 152 ependymal tumours of WHO grades I to III. Methylation status of the CDKN2A, CDKN2B and p14 ARF promoters was assessed by methylation-specific polymerase chain reaction and the genetic results were correlated to clinicopathological features. We observed promoter methylation for CDKN2A in 21% (26/123) of tumours, for CDKN2B in 32% (23/71) and p14 ARF in 21% (23/108). For all three genes, posterior fossa ependymomas were less frequently methylated in paediatric patients than in adults. For CDKN2B, extracranial tumours were more frequently methylated than intracranial ones. For CDKN2B and p14 ARF, methylation was more frequent in low-grade tumours; the reverse was observed for CDKN2A. CDKN2A, CDKN2B and p14 ARF promoters were methylated in 21-32% of the tumours. Frequencies of methylation varied according to clinicopathological features. This suggests a role for these genes in ependymoma tumorigenesis.