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Diverse cellular insults converge on activation of the heat shock factor 1 (HSF1), which regulates the proteotoxic stress response to maintain protein homoeostasis. HSF1 regulates numerous gene programmes beyond the proteotoxic stress response in a cell-type- and context-specific manner to promote malignancy. However, the role(s) of HSF1 in immune populations of the tumour microenvironment remain elusive. Here, we leverage an in vivo model of HSF1 activation and single-cell transcriptomic tumour profiling to show that augmented HSF1 activity in natural killer (NK) cells impairs cytotoxicity, cytokine production and subsequent anti-tumour immunity. Mechanistically, HSF1 directly binds and regulates the expression of key mediators of NK cell effector function. This work demonstrates that HSF1 regulates the immune response under the stress conditions of the tumour microenvironment. These findings have important implications for enhancing the efficacy of adoptive NK cell therapies and for designing combinatorial strategies including modulators of NK cell-mediated tumour killing.

We introduce a variant of a formalism appearing in recent work geared towards modelling systems in which a distinguished entity (leader) orchestrates the operation of an arbitrary number of identical entities (followers). Our variant is better suited for the verification of system properties involving complex arithmetic conditions. Whereas the original formalism is translated into a tractable fragment of first-order temporal logic, aiming to utilize automated (first-order temporal logic) theorem provers for verification, our variant is translated into linear integer arithmetic, aiming to utilize satisfiability modulo theories (SMT) solvers for verification. In particular, for any given system specified in our formalism, we prove, for any natural number n, the existence of a linear integer arithmetic formula whose models are in one-to-one correspondence with certain counting abstractions (profiles) of executions of the system for n time steps. Thus, one is able to verify, for any natural number n, that all executions for n time steps of any such system have a given property by establishing that said formula logically entails the property. To highlight the practical utility of our approach, we specify and verify three consensus protocols, actively used in distributed database systems and low-power wireless networks.

OBJECTIVE--To examine trends in the prevalence of diabetes among delivery hospitalizations in the U.S. and to describe the characteristics of these hospitalizations. RESEARCH DESIGN AND METHODS--Hospital discharge data from 1994 [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.11.040 Byline: Denise J. Jamieson (a), Athena P. Kourtis (a), Michael Bell (b), Sonja A. Rasmussen (c) Abstract: A report in May 2005 from the Centers for Disease Control and Prevention describing a cluster of lymphocytic choriomeningitis virus (LCMV) infections among 4 solid organ recipients has increased awareness of and clinical interest in this pathogen. Human infection with LCMV results from direct or indirect contact with rodents. LCMV has particular relevance to obstetrics, as it is likely an under-recognized abortifacient and fetal teratogen. There have been 54 cases of congenital LCMV reported since 1955, with 34 of the cases diagnosed since 1993. Chorioretinitis and hydrocephalus are the predominant characteristics among children diagnosed with congenital LCMV infection. Obstetricians should educate their pregnant patients about the risks of exposure to laboratory, pet, and wild rodents. Author Affiliation: (a) Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (b) National Center for Infectious Diseases (c) Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA Article History: Received 29 September 2005; Revised 18 November 2005; Accepted 28 November 2005 Article Note: (footnote) The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Reprints not available from the authors.

Forty women with ectopic pregnancy EP are studied considering that evidences on elevated creatine phosphokinase (CPK) as a tool for the diagnosis of EP were found conflictive. It is found that determination of CPK isoenzyme fractions can significantly enhance the diagnostic value of total maternal CPK in the prediction of ectopic pregnancy.

Introduction This article reviews and summarizes the evidence and controversies surrounding management of infants less than g months of age with fever but no evidence of infection after history and [...]

Manually increasing pressure of an ultrasonography transducer on a mother's abdomen may significantly change the measurements and thus the reproducibility of the amniotic fluid volume assessment. The amniotic fluid volumes of 40 women in their third trimester of pregnancy were measured using three predetermined operator transducer pressures. Low pressure was equal to 15 cm of water, medium pressure was at 35 cm of water, and high pressure was 65 cm of water. The medium transducer pressure is the standard for determining amniotic fluid index. Measurements obtained using the low pressure were significantly higher than standard, and measurements obtained at high pressure were significantly lower than standard. Operator pressure appears to be a potentially correctable source of error in estimating amniotic fluid volume via ultrasound. Use of low transducer pressure is recommended to obtain the highest index values and ensure that the results can be reproduced by different operators.

Sweet syndrome is rare in children but can pose a diagnostic dilemma, particularly in young infants. The presentation, heralded by unusual-appearing tender polymorphous skin lesions, typically accompanied by fever and [...]

Byline: SPYRO KOURTIS The change in the CMO's job description that we've seen over the past 10 years has the potential to do more than shorten careers. It may suffocate [...]

By Spyro Kourtis, The Hacker Group Cable marketers have always been an independent lot. It's an industry built from scratch by entrepreneurs in a relatively short period of time. The [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.02.034 Byline: Denise J. Jamieson (1), Jennifer S. Read (2), Athena P. Kourtis (1), Tonji M. Durant (3), Margaret A. Lampe (3), Kenneth L. Dominguez (3) Keywords: cesarean delivery; HIV transmission Abstract: Two studies that were published in 1999 demonstrated that cesarean delivery before labor and before the rupture of membranes (elective cesarean delivery) reduces the risk of mother-to-child transmission of the human immunodeficiency virus (HIV). On the basis of these results, the American College of Obstetricians and Gynecologists and the US Public Health Service recommend that HIV-infected pregnant women with plasma viral loads of >1000 copies per milliliter be counseled regarding the benefits of elective cesarean delivery. Since the release of these guidelines, the cesarean delivery rate among HIV-infected women in the United States has increased dramatically. Major postpartum morbidity is uncommon, and cesarean delivery among HIV-infected women is relatively safe and cost-effective. However, a number of important questions remain unanswered, including whether cesarean delivery has a role among HIV-infected women with low plasma viral loads or who receive combination antiretroviral regimens. Author Affiliation: (1) Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA (2) Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda, MD (3) Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), Centers for Disease Control and Prevention, Atlanta, GA. Article History: Received 15 December 2006; Accepted 26 February 2007 Article Note: (footnote) The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the Department of Health and Human Services.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.02.031 Byline: Michelle S. McConnell (1)(2), Jeffrey S.A. Stringer (3), Athena P. Kourtis (4), Paul J. Weidle (5), Susan H. Eshleman (6) Keywords: nevirapine; PMTCT; resistance; treatment Abstract: Nevirapine resistance has been detected in a considerable proportion of women after single-dose nevirapine (SD-NVP) for the prevention of mother-to-child human immunodeficiency virus-1 transmission. As a result, concern has been raised about the effectiveness of subsequent nevirapine-based treatment. Studies in Thailand, Botswana, and South Africa have assessed virologic treatment response after SD-NVP. These studies did not find any significant difference in virologic response for women who began treatment >6 months after SD-NVP exposure. Two studies found worse response rates in women when treatment was initiated within 6 months of SD-NVP exposure. Furthermore, 2 studies found no difference in human immunodeficiency virus transmission rates from mother to child after the receipt of SD-NVP in repeat pregnancies. These data support the use of SD-NVP as 1 option for the prevention of mother-to-child human immunodeficiency virus-1 transmission in resource-limited settings, particularly in settings where more complex regimens are not yet available. Further research in the optimization of perinatal prevention regimens is needed. Author Affiliation: (1) Thailand-US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand (2) Division of Global AIDS, Centers for Disease Control and Prevention, Atlanta, GA (3) Schools of Medicine and Public Health, University of Alabama at Birmingham, Birmingham, AL (4) Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA (5) Division of HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA (6) Johns Hopkins University, Baltimore, MD. Article History: Received 15 December 2006; Accepted 26 February 2007 Article Note: (footnote) The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the US Centers for Disease Control and Prevention.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.06.048 Byline: Mary Glenn Fowler (1), Margaret A. Lampe (2), Denise J. Jamieson (3), Athena P. Kourtis (3), Martha F. Rogers (2) Keywords: acquired immunodeficiency syndrome; human immunodeficiency virus; mother-to-child transmission; pregnancy Abstract: Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) in the United States and Europe has been a tremendous success, such that transmission rates of less than 2% have been achieved. Some key successes have also been demonstrated in resource-poor countries; however, the translation of successful interventions into public health policy has been slow because of a variety of factors such as inadequate funding and cultural, social, and institutional barriers. The issue of HIV and infant feeding in settings that lack culturally acceptable, feasible, affordable, safe, and sustainable nutritional substitutes for breast milk is a continuing dilemma. An effective preventive infant HIV vaccine would be an optimal approach to reduce HIV acquisition in the first year of life among breast-feeding infants. The challenges to eliminate new perinatal HIV infections worldwide will depend on both sustaining and expanding PMTCT interventions and effective primary HIV prevention for women, adolescents, and young adults. Author Affiliation: (1) Department of Pathology, Johns Hopkins Medical School, onsite Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda (2) Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia (3) Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia. Article History: Received 21 June 2007; Accepted 26 June 2007 Article Note: (footnote) The views expressed herein are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

The response to systemic infection and injury requires the rapid adaptation of hematopoietic stem cells (HSCs), which proliferate and divert their differentiation toward the myeloid lineage. Significant interest has emerged in understanding the signals that trigger the emergency hematopoietic program. However, the mechanisms that halt this response of HSCs, which is critical to restore homeostasis, remain unknown. Here we reveal that the E3 ubiquitin ligase Speckle-type BTB–POZ protein (SPOP) restrains the inflammatory activation of HSCs. In the absence of Spop, systemic inflammation proceeded in an unresolved manner, and the sustained response in the HSCs resulted in a lethal phenotype reminiscent of hyper-inflammatory syndrome or sepsis. Our proteomic studies decipher that SPOP restricted inflammation by ubiquitinating the innate signal transducer myeloid differentiation primary response protein 88 (MYD88). These findings unearth an HSC-intrinsic post-translational mechanism that is essential for reestablishing homeostasis after emergency hematopoiesis. Aifantis and colleagues identify the E3 ubiquitin ligase SPOP as a negative regulator of ‘emergency hematopoiesis’ in bone marrow hematopoietic stem progenitor cells.

IMPORTANCE: Increased use of long-acting reversible contraception (LARC; intrauterine devices [IUDs] and implants) has likely contributed to declining US teenage pregnancy and birth rates, yet sexually transmitted infection (STI) rates among teenagers remain high. While LARC methods are highly effective for pregnancy prevention, they, as with all nonbarrier methods, do not protect against STIs, including HIV. Studies of the general adolescent population suggest condom use is lower among LARC vs non-LARC hormonal methods users (birth control pill, contraceptive patch, vaginal ring, or injection). Despite the high use of LARC among postpartum teenagers, no studies have examined whether condom use differs by contraceptive method in this population. OBJECTIVE: To compare condom use among sexually active postpartum teenagers using LARC vs those using non-LARC hormonal methods. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis using 2012 to 2015 data from the Pregnancy Risk Assessment Monitoring System (PRAMS), a multisite and population-based surveillance system that collects data on maternal attitudes, behaviors, and experiences before, during, and shortly after pregnancy. We used data from 37 sites. Using multivariable survey-weighted logistic regression, we assessed the association of condom use by contraceptive methods. Participants were teenage mothers (≤19 years) with a recent live birth reporting LARC or non-LARC hormonal method use. Data were analyzed between March 2018 and April 2018. MAIN OUTCOMES AND MEASURES: Condom use with LARC vs condom use with non-LARC hormonal methods. RESULTS: Among the 5480 (weighted N = 245 847) postpartum teenage mothers in our sample, most were aged 18 to 19 years, unmarried, had current Medicaid coverage, were first-time mothers, had reported their pregnancy was unintended, and almost half were non-Hispanic white. Overall, condom use was reported by 28.8% of these teenagers. Users of LARC compared with non-LARC hormonal methods were half as likely to use condoms (17.8% vs 35.6%; adjusted prevalence ratio [aPR], 0.50; 95% CI, 0.41-0.60). Users of IUDs (15.1%) were less likely to report condom use than those using an implant (21.5%; aPR, 0.70; 95% CI, 0.51-0.98), patch, ring, or injection users (24.9%; aPR, 0.61; 95% CI, 0.47-0.79), and pill users (47.2%; aPR, 0.32; 95% CI, 0.25-0.40). CONCLUSIONS AND RELEVANCE: Self-reported condom use was low overall among postpartum teenage mothers and lower among users of LARC vs non-LARC hormonal methods. Given the high rates of STIs among teenage mothers combined with higher use of LARC among postpartum teenaged mothers, interventions to promote condom use for STI/HIV prevention during the postpartum period are critically important.

The effects of maternal tenofovir use on infant bone mineral content (BMC) and bone mineral density (BMD) were evaluated in a pilot study of HIV/Hepatitis B-coinfected pregnant women in China. BMD and BMC were assessed at age 6 months of life in 14 tenofovir-exposed and 13 unexposed infants. Trends toward lower BMC and BMD were observed in infants exposed to maternal tenofovir but were not statistically significant.

Cellular transformation is accompanied by extensive rewiring of many biological processes leading to augmented levels of distinct types of cellular stress, including proteotoxic stress. Cancer cells critically depend on stress-relief pathways for their survival. However, the mechanisms underlying the transcriptional initiation and maintenance of the oncogenic stress response remain elusive. Here, we show that the expression of heat shock transcription factor 1 (HSF1) and the downstream mediators of the heat shock response is transcriptionally upregulated in T cell acute lymphoblastic leukemia (T-ALL). Hsf1ablation suppresses the growth of human T-ALL and eradicates leukemia in mouse models of T-ALL, while sparing normal hematopoiesis. HSF1 drives a compact transcriptional program and among the direct HSF1 targets, specific chaperones and co-chaperones mediate its critical role in T-ALL. Notably, we demonstrate that the central T-ALL oncogene NOTCH1 hijacks the cellular stress response machinery by inducing the expression of HSF1and its downstream effectors. The NOTCH1 signaling status controls the levels of chaperone/co-chaperone complexes and predicts the response of T-ALL patient samples to HSP90 inhibition. Our data demonstrate an integral crosstalk between mediators of oncogene and non-oncogene addiction and reveal critical nodes of the heat shock response pathway that can be targeted therapeutically.

Lead nurture requires good timing and the analysis of customer's needs. Lead generation process automation might be a good method for improving marketing processes, but marketers should also consider the benefits of eliminating the entire process. Ways of streamlining and improving marketing systems are provided.

The use of emotional appeal in the sales pitch targeting the C-level executives is discussed. The methodology required to approach C-level executives is discussed.

Suggestions have been provided to marketers for making effective leads in direct mails to customers.

A microsite is one of the most powerful ways to interact with leads in a personal way as in business-to-business direct marketing, much of lead management success involves control. Microsites are online worlds, each designed as an integral part of its own mailing or e-mail.

The sales team drops most marketing leads, as they are not qualified or ready to deal with at that time. Leads need to be distinguished and nurtured along with good communication strategies to get a final positive decision in oneEs favor. The role of the marketerEs in todayEs world is not just to identify leads, but in collaboration with the sales, the leads have to be qualified and formal communication created so that the leads ultimately generate business.

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A methodology has been developed and is presented for the economic valuation of Ecosystem Services (ES) provided in the case of restoration of an existing irrigation canal to a riparian corridor-linear park. The application is in an existing canal in Chrissoupolis, North Greece. Using the Contingent Valuation Method (CVM), a survey was conducted through questionnaires and personal interviews in 98 residents in July 2014. The survey results were extracted by two different ways: with the use of the Analytical Hierarchy Process (AHP) and simple statistical analysis. AHP was used in extracting the Willingness to Pay (WTP) for the restoration. Results of simple statistical analysis indicate that residents are willing to pay for the restoration an average of 11.44 € per year per resident or 75,216 € in total. The respective results from the implementation of the AHP method indicated a WTP of 49.45 € per year per resident or 325,000 € in total. This study highlights the need to consider ES and their value in future ecosystem restoration.

This study presents the results of a pilot project in which the use of drones for teaching primary school students was examined. In order to implement the project, a framework for their integration in teaching was developed, based on contemporary learning theories. Also, three short interventions were planned and carried out. Although teaching units from the mathematics, physics, and geography courses were selected, the underlying topic was common, namely, metric measurement conversions. The target group was 40 fifth-grade primary school students, divided into two groups. The first group was taught with the use of drones while the second was taught conventionally. Data were collected by means of evaluation sheets and a questionnaire. Results indicated that students in the drones group outperformed students in the conventional teaching group in the Maths evaluation sheet and in all the delayed post-tests. In the other two cases (Physics and Geography evaluation sheets), the results were the same. Students’ attitudes toward drones were highly positive. Finally, the implications of the findings for education are also discussed.

Introduction Despite enthusiasm for metal-on-metal bearings, disappointing short- to mid-term outcomes has all but halted the use of this bearing articulation. This review presents mid-term results for the ReCap Magnum total hip replacement.Patients and Methods This prospective study evaluated 79 ReCap/Magnum/Taperloc total hip replacements with mean follow-up of 7.1 (range 3.7-9.2) years. 43 were female and 36 male. Metal ions were measured and radiographic measurement included a ‘margin of safety’ angle to quantify risk of edge loading. When a clinical suspicion of adverse reaction to metal debris was present, patients had metal artefact reduction sequence MRI. Harris Hip Score and Oxford Hip Score evaluated functional outcome and SF-12 and EQ-5L-5D assessed quality of life at final follow-up.Results 7 hips were revised indicating 91.1% survivorship at 7.1 years. Postoperative Harris Hip Score and Oxford Hip Score significantly improved. Females and symptomatic patients predicted increased metal ions. Margin of safety correlated with postoperative Oxford Hip Score. Symptomatic hips and positive MRI showed reduced survivorship.Conclusions Compared to more traditional bearings like metal or ceramic on polyethylene the overall outcome of this ReCap/Magnum/Taperloc study cohort is modest. It is felt that further failures will occur in this group therefore cautious interpretation of the results is justified given the potential for reduced survival outcomes.

BackgroundThere is limited information on rates of STIs in Jamaica due to syndromic management and limited aetiological surveillance. We examined the prevalence of Chlamydia trachomatis(CT), Neisseria gonorrhoeae(NG) and Trichomonas vaginalis(TV) and characteristics associated with STIs among sexually active women who participated in a randomised trial of a progestin implant initiation in Jamaica (the Sino-Implant Study (SIS)).MethodsSIS was a randomised trial conducted in Kingston, Jamaica, from 2012 to 2014 to evaluate whether initiation of the Sino-Implant (II) led to more unprotected sex among women ages 18–44 years. Data collected included self-reported demographic, sexual behaviour information; and vaginal swabs collected at baseline, 1-month and 3-month follow-up visits for a biomarker of recent semen exposure (prostate-specific antigen (PSA)) and for STIs. We examined associations between STIs and PSA, demographics, sexual behaviour and insertion of an implant, with a repeated-measures analysis using generalised estimating equations (SAS Institute, V.9.3).ResultsRemnant vaginal swabs from 254 of 414 study participants were tested for STIs. At baseline, 29% of participants tested for STIs (n=247) had laboratory-confirmed CT, 5% NG, 23% TV and 45% any STI. In a repeated-measures analysis adjusted for study arm (immediate vs delayed implant insertion), those with PSA detected did not have an increased prevalence of any STI (prevalence ratio (PR)=1.04 (95% CI 0.89 to 1.21)), whereas prevalence decreased for each 1-year increase in age (PR=0.98 (95% CI 0.97 to 0.99)). Immediate implant insertion was not associated with increases in any STI in subsequent visits (PR=1.09 (95% CI 0.94 to 1.27)).ConclusionsAlthough the prevalence of laboratory-confirmed STIs was high, the immediate initiation of a contraceptive implant was not associated with higher STI prevalence rates over 3 months.Trial registration numberNCT01684358.

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ABSTRACTCytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.