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BackgroundBioengineered T cell treatments for acute myeloid leukemia (AML) are challenged by near universal expression of leukemia antigens on normal hematopoietic stem/progenitor cells:1 2 ‘on target/off tumor‘ activity may cause... more
BackgroundBioengineered T cell treatments for acute myeloid leukemia (AML) are challenged by near universal expression of leukemia antigens on normal hematopoietic stem/progenitor cells:1 2 ‘on target/off tumor‘ activity may cause myelosuppression while sustained antigen exposure can lead to T cell exhaustion.3 In addition, splicing variants may allow antigen escape. We hypothesize that by using a novel CD33-C2-specific single domain VHH antibody as the antigen targeting domain in dimerizing agent-regulated immunoreceptor complex T cells (DARIC T cells), we will enable pharmacologically-controllable targeting of CD33, allowing eradication of leukemia expressing either of the major splice variants of CD33: i.e., full-length CD33 or CD33ΔE2.MethodsWe engineered DARIC-expressing lentiviral vectors containing encoding separated CD33-C2-specific antigen binding and 41BB-CD3zeta signaling chains that heterodimerize following addition of rapamycin via embedded FKBP12 and FRB* domains.4 Per...
Functional and molecular MRI techniques are capable of measuring biologic properties of tumor tissue. Knowledge of these biological properties may improve radiation treatment by more accurately identifying tumor volumes, characterizing... more
Functional and molecular MRI techniques are capable of measuring biologic properties of tumor tissue. Knowledge of these biological properties may improve radiation treatment by more accurately identifying tumor volumes, characterizing radioresistant subvolumes of tumor before radiation therapy (RT), and identifying recurrent disease after RT. Intravoxel incoherent motion MRI, blood oxygenation level-dependent MRI, tissue oxygenation level-dependent MRI, hyperpolarized C MRI, and chemical exchange saturation transfer MRI are relatively new MRI techniques that have shown promise for contributing to RT planning and response assessment. This review critically evaluates these emerging MR techniques, their potential role in RT planning, utility to date, and challenges to integration into the current clinical workflow.
The oral mucosa is one of the most rapidly dividing tissues in the body and serves as a barrier to physical and chemical insults from mastication, food, and microorganisms. Breakdown of this barrier can lead to significant morbidity and... more
The oral mucosa is one of the most rapidly dividing tissues in the body and serves as a barrier to physical and chemical insults from mastication, food, and microorganisms. Breakdown of this barrier can lead to significant morbidity and potentially life-threatening infections for patients. Determining the identity and organization of oral epithelial progenitor cells (OEPCs) is therefore paramount to understanding their roles in homeostasis and disease. Using lineage tracing and label retention experiments, we show that rapidly dividing OEPCs are located broadly within the basal layer of the mucosa throughout the oral cavity. Quantitative clonal analysis demonstrated that OEPCs undergo population-asymmetrical divisions following neutral drift dynamics and that they respond to chemotherapy-induced damage by altering daughter cell fates. Finally, using single-cell RNA-seq, we establish the basal layer population structure and propose a model that defines the organization of cells withi...
The success of immunotherapy has led to a myriad of new clinical trials. Connected to these trials are efforts to discover biomarkers providing mechanistic insight and predictive signatures for personalization. Still, the plethora of... more
The success of immunotherapy has led to a myriad of new clinical trials. Connected to these trials are efforts to discover biomarkers providing mechanistic insight and predictive signatures for personalization. Still, the plethora of immune monitoring technologies can face investigator bias, missing unanticipated cellular responses in limited clinical material. We here present a mass cytometry workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate human immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. The resulting assay enumerated ≥ 98% of peripheral immune cells with ≥ 4 positively identifying antigens. Robustness and reproducibility were demonstrated on multiple samples types, across research centers and by orthogonal measurements. Using automated analy...
Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of... more
Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases. An evaluation of comorbidities across various organ systems is warranted to understand the disease burden in adult patients. The aim of this insurance claim-based observational study was to assess the prevalence of comorbid conditions across various organ systems (e.g. dermatological, renal, respiratory, gastrointestinal, hematological, and others) among adult PKU patients compared with matched controls from the general population. This retrospective, case-controlled study selected patients f...
Switchgrass (Panicum virgatum L.) is a promising bioenergy feedstock because it can be grown on marginal land and produces abundant biomass. Recalcitrance of the lignocellulosic components of the switchgrass cell wall to enzymatic... more
Switchgrass (Panicum virgatum L.) is a promising bioenergy feedstock because it can be grown on marginal land and produces abundant biomass. Recalcitrance of the lignocellulosic components of the switchgrass cell wall to enzymatic degradation into simple sugars impedes efficient biofuel production. We previously demonstrated that overexpression of OsAT10, a BAHD acyltransferase gene, enhances saccharification efficiency in rice. Here we show that overexpression of the rice OsAT10 gene in switchgrass decreased the levels of cell wall-bound ferulic acid (FA) in green leaf tissues and to a lesser extent in senesced tissues, and significantly increased levels of cell wall-bound p-coumaric acid (p-CA) in green leaves but decreased its level in senesced tissues of the T plants under greenhouse conditions. The engineered switchgrass lines exhibit an approximate 40% increase in saccharification efficiency in green tissues and a 30% increase in senesced tissues. Our study demonstrates that o...
Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs... more
Performing chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) in lung tissue is difficult because of motion artifacts. We, therefore, developed a CEST MRI acquisition and analysis method that performs retrospective respiration gating. Our method used an acquisition scheme with a short 200-millisecond saturation pulse that can accommodate the timing of the breathing cycle, and with saturation applied at frequencies in 0.03-ppm intervals. The Fourier transform of each image was used to calculate the difference in phase angle between adjacent pixels in the longitudinal direction of the respiratory motion. Additional digital filtering techniques were used to evaluate the breathing cycle, which was used to construct CEST spectra from images during quiescent periods. Results from CEST MRI with and without respiration gating analysis were used to evaluate the asymmetry of the magnetization transfer ratio (MTR), a measure of CEST, for an egg white phantom that und...
To estimate the prevalence of use of different sources of contraceptive supplies in Britain and its variation by key demographic and behavioural characteristics. Cross-sectional probability sample survey of women and men aged 16-74 years,... more
To estimate the prevalence of use of different sources of contraceptive supplies in Britain and its variation by key demographic and behavioural characteristics. Cross-sectional probability sample survey of women and men aged 16-74 years, resident in Britain, interviewed between 2010 and 2012. Analyses reported here were of 4571 women and 3142 men aged 16-44 years who reported having vaginal sex in the past year. Those relying exclusively on sterilisation (including hysterectomy) were excluded. Sources of contraceptive supplies were categorised as: general practice, community clinic, retail and other. Prevalence of use of these sources was estimated, and associated factors examined. Some 87.0% of women and 73.8% of men accessed at least one source of contraceptive supplies in the previous year. Most women (59.1%) used general practice and most men (54.6%) used retail outlets. Community clinics were less commonly used, by 23.0% of women and 21.3% of men, but these users were younger ...
Rodents are characterized by continuously renewing incisors whose growth is fueled by epithelial and mesenchymal stem cells housed in the proximal compartments of the tooth. The epithelial stem cells reside in structures known as the... more
Rodents are characterized by continuously renewing incisors whose growth is fueled by epithelial and mesenchymal stem cells housed in the proximal compartments of the tooth. The epithelial stem cells reside in structures known as the labial (toward the lip) and lingual (toward the tongue) cervical loops (laCL and liCL, respectively). An important feature of the rodent incisor is that enamel, the outer, highly mineralized layer, is asymmetrically distributed, because it is normally generated by the laCL but not the liCL. Here, we show that epithelial-specific deletion of the transcription factor Islet1 (Isl1) is sufficient to drive formation of ectopic enamel by the liCL stem cells, and also that it leads to production of altered enamel on the labial surface. Molecular analyses of developing and adult incisors revealed that epithelial deletion of Isl1 affected multiple, major pathways: Bmp (bone morphogenetic protein), Hh (hedgehog), Fgf (fibroblast growth factor), and Notch signalin...
The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitate functional genomic analysis. To this end, we generated and sequenced a... more
The availability of a whole-genome sequenced mutant population and the cataloging of mutations of each line at a single-nucleotide resolution facilitate functional genomic analysis. To this end, we generated and sequenced a fast-neutron-induced mutant population in the model rice cultivar Kitaake (Oryza sativa ssp japonica), which completes its life cycle in 9 weeks. We sequenced 1504 mutant lines at 45-fold coverage and identified 91,513 mutations affecting 32,307 genes, i.e., 58% of all rice genes. We detected an average of 61 mutations per line. Mutation types include single-base substitutions, deletions, insertions, inversions, translocations, and tandem duplications. We observed a high proportion of loss-of-function mutations. We identified an inversion affecting a single gene as the causative mutation for the short-grain phenotype in one mutant line. This result reveals the usefulness of the resource for efficient, cost-effective identification of genes conferring specific phe...
ObjectivesTo investigate factors associated with reporting lacking interest in sex and how these vary by gender.SettingBritish general population.DesignComplex survey analyses of data collected for a cross-sectional probability sample... more
ObjectivesTo investigate factors associated with reporting lacking interest in sex and how these vary by gender.SettingBritish general population.DesignComplex survey analyses of data collected for a cross-sectional probability sample survey, undertaken 2010–2012, specifically logistic regression to calculate age-adjusted OR (AOR) to identify associated factors.Participants4839 men and 6669 women aged 16–74 years who reported ≥1 sexual partner (opposite-sex or same-sex) in the past year for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).Main outcome measureLacking interest in sex for ≥3 months in the past year.ResultsOverall, 15.0% (13.9–16.2) of men and 34.2% (32.8–35.5) of women reported lacking interest in sex. This was associated with age and physical and mental health for both men and women, including self-reported general health and current depression. Lacking interest in sex was more prevalent among men and women reporting sexually transmitted infecti...
Breakdown of marriage and cohabitation is common in Western countries and is costly for individuals and society. Most research on reasons for breakdown has focused on marriages ending in divorce and/or have used data unrepresentative of... more
Breakdown of marriage and cohabitation is common in Western countries and is costly for individuals and society. Most research on reasons for breakdown has focused on marriages ending in divorce and/or have used data unrepresentative of the population. We present prevalence estimates of, and differences in, reported reasons for recent breakdown of marriages and cohabitations in Britain. Descriptive analyses of data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability sample survey (15,162 people aged 16-74 years) undertaken 2010-2012, using computer-assisted personal interviewing. We examined participants' reported reasons for live-in partnership breakdown in the past 5 years and how these varied by gender and partnership type (married vs. cohabitation). Overall, 10.9% (95% CI: 9.9-11.9%) of men and 14.1% (13.2-15.0%) of women reported live-in partnership breakdown in the past 5 years. Mean duration of men's marriages was 14.2...
The emergency department (ED) disposition and discharge process is a critical period in a patient's transition from an acute care setting to self-care or a bridge to other healthcare providers. The emergency... more
The emergency department (ED) disposition and discharge process is a critical period in a patient's transition from an acute care setting to self-care or a bridge to other healthcare providers. The emergency physician plays a pivotal role in this process and is ultimately responsible for ensuring that patients are safely released from their care. We developed a protocol to guide residents through the ED discharge process using the mnemonic "R2D2": reassess the patient, recheck the workup, discuss the disposition plan with the attending, and finally discuss the discharge plan with the patient. The objective was to assess the effectiveness of the R2D2 discharge protocol, executed by resident physicians, in improving patients' understanding of their diagnosis and treatment plans. This is a before-and-after study in the ED of a county hospital and included all patients discharged by a resident physician from the ED 1 week before and 1 week after implementation of the R2D2 protocol. All participating resident physicians received a brief 10-minute orientation to the R2D2 protocol at the end of the first week of the study period. Consecutive patients were identified, consented, and given a brief questionnaire about their discharge by research assistants. Certain exclusion criteria applied such as inability to speak English or Spanish or no phone for follow-up. One to 2 weeks after ED discharge, patients from both groups were contacted by phone to assess their recall of their discharge instructions. Data analyses were performed using Fisher's exact, chi-square tests, or two independent-sample proportions tests as appropriate. We recruited 164 patients in the control group and 148 patients in the intervention group, totaling 312 patients. A total of 73.8% of the control group patients and 77.0% of the intervention group patients completed the follow-up. On telephone follow-up, 88% of the intervention patients knew their discharge diagnosis versus only 74% of control patients (p = 0.0062). Eighty percent of intervention patients knew their discharge treatment plan versus only 67% of control patients (p = 0.0259). The R2D2 protocol resulted in significant improvement in patients' understanding of their discharge diagnosis and treatment plan.
We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis. A... more
We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis. A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer were compared with DCE MRI and histopathology. The pHe maps of a flank model showed pHe measurements between 6.4 and 7.4, which matched with the expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the patient with metastatic ovarian cancer, the average pHe value of three adjacent tumors was 6.58, and the most reliable pHe measurements were obtained from the right posterior tumor, which favorably compared with DCE MRI and histopathological results. The average pHe of the kidney showed an average pHe of 6.73 units. The patient with high-grade invasive ductal carcinoma failed to accumulate sufficient agent to generate pHe measurements. Optimized acidoCEST MRI generated pHe measurements in a flank tumor model and could be translated to the clinic to assess a patient with metastatic ovarian cancer.
To describe actual and preferred contraceptive sources among young people in Britain and whether discordance between these is associated with markers of sexual risk behaviour or poor sexual health. Cross-sectional probability sample... more
To describe actual and preferred contraceptive sources among young people in Britain and whether discordance between these is associated with markers of sexual risk behaviour or poor sexual health. Cross-sectional probability sample survey. British general population. 3869 men and women aged 16-24 years interviewed for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) between 2010 and 2012. Reported source of contraceptive method(s) and preferred source if all were available and easily accessible. Of the 75% of young people (aged 16-24) who were heterosexually active (1619 women, 1233 men), >86% reported obtaining contraceptives in the past year. Most common sources were general practice (women, 63%) and retail (men, 60%): using multiple sources was common (women 40%, men 45%). Healthcare sources were preferred by 81% of women and 57% of men. Overall, 32% of women and 39% of men had not used their preferred source. This discordance was most common among men ...
Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Tregs) that may... more
Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25+ regulatory T cells (Tregs) that may suppress graft-versus-tumor responses. We undertook a Phase I study of donor lymphocyte infusion depleted of CD25+ T cells in hematologic malignancies relapsed after transplantation. Twenty-one subjects received CD25/Treg-depleted infusion following removal of CD25+ cells using antibody-conjugated magnetic beads. Sixteen subjects received prior cytoreductive therapy. Four were in complete remission at infusion. Two dose levels were administered: 1x107 (n=6) and 3x107 CD3+ cells/kg (n=15). Median 2.3 log-depletion of CD4+CD25+FOXP3+ Tregs was achieved. Seven subjects (33%) developed clinically significant graft-versus-host disease by one year, including one fatal case. At Dose Level 1, five subjects demonstrated progression; one had stable disease. At Dose...
We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent. A CEST-FISP MRI protocol and a diamagnetic CEST agent were... more
We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent. A CEST-FISP MRI protocol and a diamagnetic CEST agent were developed to detect GGT enzyme activity in biochemical solution. A quantitative Michaelis-Menten enzyme kinetics study was performed to confirm that catalyCEST MRI can measure enzyme activity. In vivo catalyCEST MRI studies generated pixel-wise activity maps of GGT activities. Ex vivo fluorescence imaging was performed for validation. CatalyCEST MRI selectively detected two CEST signals from a single CEST agent, whereby one CEST signal was responsive to GGT enzyme activity and the other CEST signal was an unresponsive control signal. The comparison of these CEST signals facilitated in vivo catalyCEST MRI studies that detected high GGT activity in OVCAR-8 tumors, low GGT activity in OVCAR-3 tumors, and low or no GGT activity in muscle tissues. Cataly...
In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National... more
In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals. In this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994-98 to 2009-13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990-91), Natsal-2 (1999-2001), and Natsal-3 (2010-12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18-24 years; and the prevalence of participation in education, work, and training in young mothers. Conception rates in women younger than 1...
Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4+CD25+FOXP3+ regulatory T cells (Treg). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well... more
Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4+CD25+FOXP3+ regulatory T cells (Treg). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated and did not exacerbate alloimmunity in active cGVHD. Low-dose IL-2 therapy augmented Treg in-vivo and was associated with clinical improvement. In the current phase 2 study, 35 adult patients with steroid-refractory cGVHD received daily IL-2 (1x10(6)IU/m(2)/d) for 12 weeks. Median time from transplantation and cGVHD onset was 616 (range, 270-2145) and 317 days (range, 28-1880) respectively. Two patients withdrew and 5 required IL-2 dose-reductions due to side-effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites including liver, skin, gastrointestinal tract, lung, and joint/muscle/fascia. Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and NK-cell counts rose >5-fo...
This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4 %) were taking... more
This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4 %) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism spectrum disorder (p = 0.001 and p = 0.04, respectively), and inversely associated with the youngest and oldest age categories (p = 0.001 and p = 0.04, respectively). Among those taking antipsychotics, annual metabolic monitoring rates ranged from 89 % (lipids) to 99 % (weight). Age was positively associated with glucose (p < 0.001) and lipid monitoring (p < 0.001). Adult participants with dyslipidemia (p < 0.01), prediabetes/diabetes (p = 0.04), and hypertension (p = 0.02) were significantly more likely to obtain lipid monitoring. These values exceeded previously reported rates suggesting the importance of an integrated care model.
The purpose of this study was to examine factors associated with the quality of life of lesbian, gay, bisexual, and transgender (LGBT) cancer survivors. Data were collected via a nationally advertised online short-form health survey.... more
The purpose of this study was to examine factors associated with the quality of life of lesbian, gay, bisexual, and transgender (LGBT) cancer survivors. Data were collected via a nationally advertised online short-form health survey. Factors associated with lower physical quality of life included younger age at diagnosis, cancer type, medical co-morbidities, being overweight or obese, recurrence, and current cancer treatment. Lower mental quality of life was associated with younger age, smoking, lower perceived quality of care, lower perceived support, and higher cancer-related worry. Findings highlight a need for health promotion interventions specifically for LGBT cancer survivors.
Establishing the clinical significance of symptoms of sexual dysfunction is challenging. To address this, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced two new morbidity criteria... more
Establishing the clinical significance of symptoms of sexual dysfunction is challenging. To address this, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) introduced two new morbidity criteria (duration and symptom severity) to the existing criteria of distress. This study sought to establish the impact of these three criteria on the population prevalence of sexual function problems. The data come from a national probability survey (Natsal-3) and are based on 11,509 male and female participants aged 16-74, reporting at least one sexual partner in the past year. The key outcomes were: proportion of individuals reporting proxy measures of DSM-5 problems, and the proportion of those meeting morbidity criteria. We found that among sexually active men, the prevalence of reporting one or more of four specific sexual problems was 38.2%, but 4.2% after applying the three morbidity criteria; corresponding figures for women reporting one or more of three ...
Food insecurity and its most extreme form, hunger, have increased exponentially in the United States since 2006. This essay seeks to contribute to our understanding of hunger by attending to the context of the financial crisis as an... more
Food insecurity and its most extreme form, hunger, have increased exponentially in the United States since 2006. This essay seeks to contribute to our understanding of hunger by attending to the context of the financial crisis as an organizing frame for understanding local meanings of hunger. Within a broader framework of the culture-centered approach (CCA) that works to identify and develop locally rooted solutions to food insecurity, we describe through locally grounded stories of food insecurity the financial climate where large percentages of U.S. households have been cast into poverty because of the crash of an unregulated economy. These local understandings of hunger in the context of the economy offer entry points for organizing a food-insecure coalition that seeks to address the stigma around food insecurity.
This study describes medical conditions experienced by a population-based cohort of adults with autism spectrum disorder whose significant developmental concerns were apparent during childhood. As part of a 25-year outcome study of autism... more
This study describes medical conditions experienced by a population-based cohort of adults with autism spectrum disorder whose significant developmental concerns were apparent during childhood. As part of a 25-year outcome study of autism spectrum disorder in adulthood, medical histories were collected on 92 participants (N = 69 males) who were first ascertained as children in the mid-1980s, 11 of whom were deceased at the time of follow-up. Questionnaires queried medical symptoms, disorders, hospitalizations, surgeries, and medication use. Median age at follow-up was 36 years (range: 23.5-50.5 years), and intellectual disability co-occurred in 62%. The most common medical conditions were seizures, obesity, insomnia, and constipation. The median number of medical conditions per person was 11. Increased medical comorbidity was associated with female gender (p = 0.01) and obesity (p = 0.03), but not intellectual disability (p = 0.79). Adults in this cohort of autism spectrum disorder ...
Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are... more
Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent. These results showed that the two agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of the two agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF-7 ...
Men who pay for sex (MPS) are considered a bridging population for sexually transmitted infections (STI). However, the extent, characteristics and role of MPS in transmission is poorly understood. We investigate these questions using data... more
Men who pay for sex (MPS) are considered a bridging population for sexually transmitted infections (STI). However, the extent, characteristics and role of MPS in transmission is poorly understood. We investigate these questions using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). We performed complex survey analyses of data from 6293 men aged 16-74 years resident in Britain who completed Natsal-3, a probability sample survey undertaken during 2010-2012, using computer-assisted personal interviewing and computer-assisted self-interview. 11.0% (95% CI10.1% to 11.9%) of all men reported ever paying for sex. Among MPS, 18.4% (95% CI 18.2% to 18.7%) of their lifetime sexual partners were paid. 3.6% (95% CI 3.1% to 4.2%) of men had paid for sex in the past 5 years. Partners of MPS constitute 14.7% of all reported partners and MPS report 15.6% of all reported STI diagnoses in the past 5 years. Paying for sex in the past 5 years was strongly ass...
To assess progress in meeting young people's sex education needs in Britain by examining the current situation and changes over the past 20 years in sources of information about sexual matters and unmet information needs.... more
To assess progress in meeting young people's sex education needs in Britain by examining the current situation and changes over the past 20 years in sources of information about sexual matters and unmet information needs. Cross-sectional probability sample surveys. British general population. 3869 men and women aged 16-24 years, interviewed 2010-2012 for the third National Survey of Sexual Attitudes & Lifestyles (Natsal-3), compared with 16-24 year-olds in Natsal-1 (1990-1991; 792 men and women) and Natsal-2 (1999-2001; 2673 men and women). Reported source of information about sexual matters, unmet information needs and preferred source of additional information. Between 1990 and 2012, the proportion citing school lessons as their main source of information about sexual matters increased from 28.2% (95% CI 24.6 to 32.1) to 40.3% (95% CI 38.6 to 42.1). In 2010-2012, parents were reported as a main source by only 7.1% (95% CI 5.8 to 8.7) of men and 14.1% (95% CI 12.6 to 15.7) of w...
To examine variation in source of information about sexual matters by sociodemographic factors, and associations with sexual behaviours and outcomes. Cross-sectional probability sample survey. British general population. 3408 men and... more
To examine variation in source of information about sexual matters by sociodemographic factors, and associations with sexual behaviours and outcomes. Cross-sectional probability sample survey. British general population. 3408 men and women, aged 17-24 years, interviewed from 2010-2012 for third National Survey of Sexual Attitudes and Lifestyles. Main source of information (school, a parent, other); age and circumstances of first heterosexual intercourse; unsafe sex and distress about sex in past year; experience of sexually transmitted infection (STI) diagnoses, non-volitional sex or abortion (women only) ever. Citing school was associated with younger age, higher educational level and having lived with both parents. Citing a parent was associated, in women, with lower educational level and having lived with one parent. Relative to other sources, citing school was associated with older age at first sex (adjusted HR 0.73 (95% CI 0.65 to 0.83) men, 0.73 (0.65 to 0.82) women), lower li...
Oxidative stress in the RPE is widely accepted as a contributing factor to AMD. We have previously shown that ribozyme-mediated reduction in the antioxidant enzyme manganese superoxide dismutase (MnSOD) leads to some of the features of... more
Oxidative stress in the RPE is widely accepted as a contributing factor to AMD. We have previously shown that ribozyme-mediated reduction in the antioxidant enzyme manganese superoxide dismutase (MnSOD) leads to some of the features of geographic atrophy in mice. To develop a mouse model independent of viral injection, we used a conditional knockout of the Sod2 gene in the RPE to elevate mitochondrial oxidative stress in that cell layer. Experimental mice in which exon 3 of Sod2 was flanked by loxP sites were also transgenic for PVMD2-rtTA and tetO-PhCMV cre, so that cre recombinase was expressed only in the RPE. Pups of this genotype (Sod2(flox/flox)VMD2cre) were induced to express cre recombinase by feeding doxycycline-laced chow to nursing dams. Controls included mice of this genotype not treated with doxycycline and doxycycline-treated Sod2(flox/flox) mice lacking the cre transgene. Expression of cre in the RPE was verified by immunohistochemistry, and deletion of Sod2 exon 3 in...
Men who have sex with men (MSM) engage in several harmful health behaviors more frequently than do non-MSM. Meanwhile, evidence suggests that MSM experience barriers to accessing health care. To investigate health care disparities and... more
Men who have sex with men (MSM) engage in several harmful health behaviors more frequently than do non-MSM. Meanwhile, evidence suggests that MSM experience barriers to accessing health care. To investigate health care disparities and health behaviors, we ...

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