"It made all the difference": a qualitative study of parental experiences with pediatric obstructive sleep apnea detection.

STUDY OBJECTIVES: To assess parental experience of their child's obstructive sleep apnea (OSA) detection process and inform the development of interventions and health communication strategies to improve OSA detection. METHODS: Semistructured interviews were conducted with 30 parents of children (ages 3-14) who snored and were referred for an overnight polysomnogram (PSG). Parents (60.0% Black race, 93.3% mothers) described how their child was referred for PSG and their perceptions and feelings throughout the detection process. Parents also completed an OSA knowledge measure. Interview data were analyzed using a descriptive approach and thematic analysis was conducted using the NVivo 12 software system. RESULTS: Twenty-one themes were identified across 5 categories (first steps; PSG facilitators and barriers; health information; health care experiences; parent experiences). Respondents experienced multiple pathways to OSA detection, with more than half of referrals initiated by parental concerns (vs. screening efforts). Parents reported a willingness to take any necessary steps to help their child. Both barriers and facilitators to completing a PSG were described. Parents observed both nighttime and daytime symptoms related to OSA in their child but often did not connect the symptoms to each other until later in the process. Participants had varying degrees of OSA knowledge, with a mean knowledge score of 56% correct (range 10%-90% correct). CONCLUSIONS: Parental experiences highlight aspects of the health care system that are both effective and ineffective in detecting children with OSA. Implications include a need for strategies to promote timely detection and to provide parents with accurate information about pediatric OSA. CITATION: Honaker SM, Gopalkrishnan A, Brann M, Wiehe S, Clark AA, Chung A. "It made all the difference": a qualitative study of parental experiences ith pediatric obstructive sleep apnea detection. J Clin Sleep Med. 2022;18(8):1921-1931.

Pausing Mid-Sentence: An Ecological Model Approach to Language Disorder and Lived Experience of Young Male Offenders.

International research evidence has firmly established a high prevalence of language disorder in young offender populations. Less is known about young offenders' perspectives on their own language abilities. The study recruited an opportunity sample of 10 young men in custody at a Scottish youth offending institution who had recent experience of segregation. This mixed-methods study investigated participants' views on their language and communication abilities to inform future support and intervention, and formal language assessment was also administered to investigate indicative prevalence of language disorder within the sample. It focused on their communication with professionals and peers in justice, education and welfare settings. Results of standardised language assessment indicated the presence of language disorder in 44% (n = 4) of the sample (n = 9). Thematic analysis of interview data led to formulation of three themes: Valuing Communication, Literacy and Learning; Exerting Control; and Seeking Support. The first theme is discussed with reference to Bronfenbrenner's Bioecological Model. Participants offered reflective and rich views on their lived experience. They provided perspectives on features of successful interaction with peers and authority figures, importance of effective communication and the difficulties they encountered. This study argues for additional communication support for young people in the justice system.

Improving Patient-Centered Communication about Sudden Unexpected Death in Epilepsy through Computerized Clinical Decision Support.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a rare but fatal risk that patients, parents, and professional societies clearly recommend discussing with patients and families. However, this conversation does not routinely happen. OBJECTIVES: This pilot study aimed to demonstrate whether computerized decision support could increase patient communication about SUDEP. METHODS: A prospective before-and-after study of the effect of computerized decision support on delivery of SUDEP counseling. The intervention was a screening, alerting, education, and follow-up SUDEP module for an existing computerized decision support system (the Child Health Improvement through Computer Automation [CHICA]) in five urban pediatric primary care clinics. Families of children with epilepsy were contacted by telephone before and after implementation to assess if the clinician discussed SUDEP at their respective encounters. RESULTS: The CHICA-SUDEP module screened 7,154 children age 0 to 21 years for seizures over 7 months; 108 (1.5%) reported epilepsy. We interviewed 101 families after primary care encounters (75 before and 26 after implementation) over 9 months. After starting CHICA-SUDEP, the number of caregivers who reported discussing SUDEP with their child's clinician more than doubled from 21% (16/75) to 46% (12/26; p = 0.03), and when the parent recalled who brought up the topic, 80% of the time it was the clinician. The differences between timing and sampling methodologies of before and after intervention cohorts could have led to potential sampling and recall bias. CONCLUSION: Clinician-family discussions about SUDEP significantly increased in pediatric primary care clinics after introducing a systematic, computerized screening and decision support module. These tools demonstrate potential for increasing patient-centered education about SUDEP, as well as incorporating other guideline-recommended algorithms into primary and subspecialty cares. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT03502759.

Different Factors Associated with 2-Year Outcomes in Patients with Branch versus Central Retinal Vein Occlusion Treated with Ranibizumab.

PURPOSE: To investigate characteristics associated with visual and anatomic outcomes in branch and central retinal vein occlusion (BRVO and CRVO) patients treated with ranibizumab. DESIGN: Post hoc analysis of patients with BRVO and CRVO from 2 multicenter clinical trials who completed month 12 of the HORIZON extension trial. PARTICIPANTS: 205 patients with BRVO and 181 patients with CRVO who completed month 12 of the extension trial. METHODS: With the use of logistic regression, covariates with a P value < 0.20 from univariate analysis were included in multivariate models to identify independent factors associated with a given outcome (at P < 0.05), with preset variables of disease duration and original treatment assignment. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) ≥20/40 (≥70 letters), gain ≥15 letters, and central subfield thickness (CST) ≤250 µm at HORIZON month 12. RESULTS: In patients with BRVO, good baseline BCVA (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.30-1.79), male sex (OR, 2.48; 95% CI, 1.20-5.13), and normal hematocrit (low vs. normal, OR, 0.26; 95% CI, 0.12-0.59) predicted BCVA ≥20/40; high central foveal thickness (OR, 1.03; 95% CI, 1.01-1.04) and normal hematocrit (low vs. normal, OR, 0.31; 95% CI, 0.15-0.66) predicted BCVA improvement ≥15 letters; and extensive baseline subretinal fluid modestly predicted CST ≤250 µm (OR, 1.08; 95% CI, 1.00-1.16). In patients with CRVO, good baseline BCVA (OR, 1.59; 95% CI, 1.35-1.89), never smoking (OR, 2.80; 95% CI, 1.27-6.17), and young age (OR, 0.58; 95% CI, 0.41-0.82) predicted BCVA ≥20/40; never smoking (OR, 2.13; 95% CI, 1.03-4.39), young age (OR, 0.41; 95% CI, 0.28-0.59), poor baseline BCVA (OR, 0.82; 95% CI, 0.73-0.93), hypertension (OR, 4.47; 95% CI, 1.70-11.75), and low diastolic ocular perfusion pressure (OPP) throughout the study (OR, 0.39; 95% CI, 0.21-0.72) predicted BCVA improvement ≥15 letters; and young age (OR, 0.65; 95% CI, 0.47-0.90), lower mean hematocrit (low vs. normal, OR, 2.81; 95% CI, 1.06-7.49), high systolic OPP throughout the study (OR, 1.61; 95% CI, 1.14-2.27), large areas of central hemorrhage (OR, 1.44; 95% CI, 1.04-2.00), and no subretinal fluid (OR, 2.15; 95% CI, 1.06-4.40) predicted CST ≤250 µm. CONCLUSIONS: There are substantial differences in good outcome factors in CRVO versus BRVO, suggesting differences in pathophysiology. Young age, never smoking, hemodilution, and hypertension/high systolic perfusion pressure are more beneficial in CRVO, suggesting that avoidance of sluggish blood flow and maintenance of perfusion may be particularly important in CRVO.

Developing a Cancer-Focused Library Survey - Assessing the Current Environment and Planning for the Future.

The primary goal of this project is to understand how each National Cancer Institute-designated cancer center library, and all libraries that support cancer research, function within their institutions. Through an in-depth survey focused on three major areas (staff, content and tools procurement, and user services), the research team hopes to determine how a cancer-centric library can be successful in supporting quality patient care, research excellence, and education. Additionally, the survey will examine the necessary minimum staffing levels for librarians and information professionals based on organizational size and degree of research focus. The survey will seek out the new skills librarians will need to deliver optimal services. The survey will also explore how content libraries purchase reflects and maps to constituents' current medical and research activities. Libraries within a research intense environment have a responsibility to align with researchers and health care professionals to provide resources and services that support their workflows. Cancer libraries need to be attuned to their institutions' missions, whether that includes excellent patient care, research endeavors, or cutting-edge educational programs. The information gathered from the survey will provide data for this research team to define the vision and standards of excellence for a cancer specialized research library.

Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.

Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t+ cells, then re-activated, and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were given transduced T cells and IL-2, and were followed for clinical and biological responses. Transduced T cells were detected in the circulation of three treated patients for the duration of observation (42, 523, and 255 days). Patient 1 tolerated the infusion well but died from progressive disease after 6 weeks. Patient 2 had a partial response by RECIST criteria then progressed. After progressing, Patient 2 was given high-dose IL-2 and subsequently achieved complete remission, coinciding with the development of vitiligo. Patient 3 had a mixed response that did not meet RECIST criteria for a clinical response and developed vitiligo. In two of these three patients, adoptive transfer of tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had clinical and/or biological activity without serious adverse events.

Correction to: Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.

The authors would like to make the following corrections to the published article.

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment.

Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband's affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region.

Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia.

AIM: Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia. METHOD: Genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years). RESULTS: In the clinical language-impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified. INTERPRETATION: The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non-verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals.

Phase I pilot study of oxaliplatin, infusional 5-FU, and cetuximab in recurrent or metastatic head and neck cancer.

Platinum-based therapy is active in advanced head and neck squamous cell carcinoma (HNSCC). Patients with inoperable recurrent or metastatic HNSCC have a poor prognosis; many have difficulty tolerating cisplatin-based regimens. Oxaliplatin has antitumor activity without many of the toxicities of cisplatin. We conducted a phase I pilot study to investigate the dose limitation of oxaliplatin with 5-fluorouracil (5-FU) and cetuximab in patients with untreated recurrent or metastatic HNSCC. The planned dose escalation schedule included: dose level 1: oxaliplatin 100 mg/m(2) day 1, 5-FU CIV 750 mg/m(2)/day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly) every 21 days. Dose level 2: oxaliplatin 130 mg/m(2) day 1, 5-FU CIV 1,000 mg/m(2)/day over 96 h beginning day 1, and the same dose and schedule of cetuximab. Seven patients were accrued at dose level 1 and three at dose level 2. Dose level 1 toxicity included grade 1-2 stomatitis, fatigue, acneiform rash, and anemia, and grade 1 nausea and transaminitis. Dose level 2 toxicity was unacceptable: 2 of 3 patients experienced grade 4 toxicities (stomatitis, diarrhea, and acute renal failure) requiring hospitalization with one treatment-related death. Accrual was therefore closed with dose level 1 considered the maximum tolerated dose. Observed responses were short-lived. The regimen of oxaliplatin 100 mg/m(2) day 1, infusional 5-FU 750 mg/m(2)/day over 96 h beginning day 1, and cetuximab 400 mg/m(2) day 1 (then 250 mg/m(2) weekly), every 21 days, has manageable toxicity; these doses are recommended for phase II evaluation in the treatment for unresectable or metastatic HNSCC.

Multiplexed microsatellite loci in American crow (Corvus brachyrhynchos): a severely affected natural host of West Nile virus.

Recent advances in high throughput molecular techniques have allowed the development of cost- and time-effective libraries of molecular markers, such as microsatellites, for population genetic studies in non-model species. The American crow, Corvus brachyrhynchos, is recognized to be one of the species that has been most negatively affected by the emergence of West Nile virus (WNV) in North America in 1999. Genetic monitoring of the process of a declining population after the introduction of an infectious disease can provide insights into the demographic and evolutionary impact of a pathogen in a natural host population over time. In this study, shotgun pyrosequencing and validation of previously published cross-species markers were the approaches used to identify and develop a set of 32 polymorphic loci for the C. brachyrhynchos. Since the American crow is morphologically similar to the sympatric species Fish crow (Corvus ossifragus), we also designed a real-time PCR protocol to rapidly differentiate these two species using a set of primers and probes that can discriminate a section of the COI gene at the mitochondrial DNA. These new markers together with a faster method for species verification will allow further detailed studies to characterize and compare genetic diversity of historic and contemporary C. brachyrhynchos populations.

Quality of life in patients postcolectomy for pediatric-onset ulcerative colitis.

BACKGROUND: Ulcerative colitis in children can have a negative effect on quality of life (QOL). METHODS: We included 16 of 31 patients who underwent colectomy for ulcerative colitis before 20 years of age between 1980 and 2005 at University of California in San Francisco Benioff Children's Hospital. A disease-specific QOL questionnaire (Inflammatory Bowel Disease Questionnaire-32), validated for adults, was used to determine QOL and an additional questionnaire addressing bowel function and reproductive health in long-term follow-up of these patients. RESULTS: Median age at the time of survey was 20.3 years (17.9-25.3), and time postcolectomy was 6.9 years (4.8-9.0). Mean total score was 159.7 ± 43.3 (58-210). Two patients (12.5%) had scores of ≥ 200, 12 (75.0%) had 101 to 199, and 2 (12.5%) had ≤ 100. Patients ages 18 years or younger at the time of survey showed higher QOL, particularly in emotional health (P=0.020), social function (P=0.014), and overall QOL (P=0.009). Social function scored highest of all of the systems (median 7; interquartile range 4-7). Patients with scores ≤ 100 had repeated episodes of pouchitis (16-30) compared with the other 14 patients (0-3). Children who were diagnosed ages 12 years or younger tended to have higher QOL (p=0.072). Years postcolectomy did not correlate to QOL. Eleven patients were sexually active. Two males had feelings of impotence and decreased libido, and 6 females experienced dyspareunia. Three women tried unsuccessfully to conceive after colectomy. One woman became pregnant 4 times, each leading to miscarriage. CONCLUSIONS: Younger age at time of colectomy, diagnosis, and survey show higher QOL. Highest satisfaction was found in ability to attend school, work, and social engagements. Pouchitis continued to be an issue for a small number of the patients, with 2 patients having recurring episodes that severely affected QOL. Patients reported decreased sexual activity and fertility at the time of survey due to colectomy, especially for females.

An intact medial preoptic area is necessary for zaprinast to modulate paced mating behavior in female rats.

The present study examined the interaction between the regulation of paced mating behavior by the medial preoptic area (mPOA) and by the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway, as modulated by zaprinast, a phosphodiesterase inhibitor. Rats receiving mPOA or sham lesions were tested for paced mating behavior. Subsequently, rats were treated with zaprinast (3 mg/kg) before a second paced mating test. The expected lengthening of contact-return latencies following intromissions and ejaculations was observed in rats with mPOA lesions relative to rats with sham lesions. In addition, rats with sham lesions responded to zaprinast with a lengthening of contact-return latency following ejaculation. Contact-return latencies did not change in response to zaprinast in rats with mPOA lesions. These results demonstrate that the alterations in paced mating behavior observed in rats with mPOA lesions persist despite manipulation of the nitric oxide-cyclic guanosine monophospate pathway.

The role of the androgen receptor in anabolic androgenic steroid-induced aggressive behavior in C57BL/6J and Tfm mice.

Humans self-administer anabolic androgenic steroids (AAS) at superphysiological doses for the purpose of building muscle mass and enhancing physique whereas considerably lower doses of AAS are prescribed in the clinic to treat a variety of disorders. A number of studies have demonstrated that individual AAS influence aggressive behavior in rats and mice, but few studies have examined the aggression-enhancing effects of combinations of AAS. Using the resident-intruder paradigm, Experiment 1 determined whether a cocktail of commonly abused AAS increased aggressive behavior in gonadally-intact male C57BL/6J mice and examined whether the androgen receptor (AR) was involved. Mice given either AAS cocktail or the cocktail and the AR antagonist, flutamide, for 6 weeks were subject to three weekly tests in which the percentage of mice that fought, the latency to initiate an aggressive event and the number of aggressive events per 5-min-fight session were recorded. In C57BL/6J mice, 6 weeks of AAS administration increased the likelihood of fighting, however, within the subset of mice that engaged in aggression, AAS did not specifically modulate the latency to fight or the number of aggressive events per fight. In addition, co-administration of flutamide only slightly altered the likelihood that mice given AAS will initiate a fight. Experiment 2 examined the aggression-promoting effects of AAS in gonadally-intact adult testicular feminization mutant (Tfm) mice, which are deficient in functional ARs. Overall, fewer Tfm mice compared to C57BL/6J mice fought in both drug conditions (vehicle or AAS). Taken together, these data suggest that given the presence of AR during development, AAS enhance adult male aggression in C57BL/6J mice through AR-independent and AR-dependent pathways. In contrast, in adult Tfm mice, the likelihood of AAS-enhanced aggression in adulthood is significantly reduced.

The display of paced mating behavior in a rat model of endometriosis.

Endometriosis is a disorder associated with chronic pelvic pain and ill effects on women's sexual health. The present study examined the effects of pelvic endometriotic implants on the display of paced mating behavior in female rats. Approximately 2 months after the surgical induction of endometriosis, rats were tested for paced mating behavior during proestrus (Experiment 1) or after bilateral ovariectomy and hormone replacement (Experiment 2). Although endometriotic implants were confirmed at autopsy, rats with surgical endometriosis in both experiments exhibited normal patterns of paced mating behavior. The positive relationship between implant material and contact-return latency following ejaculation in Experiment 2 suggests that the sensitivity to vigorous mating stimulation may be influenced by endometriosis.

Gastroesophageal reflux is not associated with dental erosion in children.

BACKGROUND & AIMS: Dental erosion is a complication of gastroesophageal reflux (GER) in adults; in children, it is not clear if GER has a role in dental pathologic conditions. Dietary intake, oral hygiene, high bacterial load, and decreased salivary flow might contribute independently to GER development or dental erosion, but their potential involvement in dental erosion from GER is not understood. We investigated the prevalence of dental erosion among children with and without GER symptoms, and whether salivary flow rate or bacterial load contribute to location-specific dental erosion. METHODS: We performed a cross-sectional study of 59 children (ages, 9-17 y) with symptoms of GER and 20 asymptomatic children (controls); all completed a questionnaire on dietary exposure. Permanent teeth were examined for erosion into dentin, erosion locations, and affected surfaces. The dentist was not aware of GER status, and the gastroenterologist was not aware of dental status. Stimulated salivary flow was measured and salivary bacterial load was calculated for total bacteria, Streptococcus mutans, and Lactobacilli. RESULTS: Controlling for age, dietary intake, and oral hygiene, there was no association between GER symptoms and dental erosion by tooth location or affected surface. Salivary flow did not correlate with GER symptoms or erosion. Erosion location and surface were independent of total bacteria and levels of Streptococcus mutans and Lactobacilli. CONCLUSIONS: Location-specific dental erosion is not associated with GER, salivary flow, or bacterial load. Prospective studies are required to determine the pathogenesis of GER-associated dental erosion and the relationship between dental caries to GER and dental erosion.

Genitosensory nerve modulation of paced mating behavior: evidence for pelvic, but not hypogastric, nerve influence.

The pelvic nerve is known to play a role in the behavioral and neurochemical responses exhibited during paced mating behavior. The present study extended the analysis of the contribution of the genitosensory nerves to the display of paced mating behavior to include bilateral hypogastric nerve transection, bilateral pelvic nerve transection, or transection of both the hypogastric and pelvic nerves. Rats with pelvic nerve transection were less likely to exit the male compartment, took longer to exit the male compartment following intromissions, and returned to the male more quickly following intromissions compared to rats with an intact pelvic nerve. In contrast, hypogastric nerve transection alone did not affect paced mating and had no modulating effect on the paced mating behavior of rats with pelvic nerve transection. Our results support the view that key aspects of paced mating behavior are modulated by signals transmitted via the pelvic nerve, without any discernable contribution from the hypogastric nerve.

Androgen inhibition of sexual receptivity is modulated by estrogen.

Sexual receptivity induced in ovariectomized rats by the long-term administration of estradiol benzoate (EB) can be inhibited by concurrent administration of androgens. Experiment 1 examined the role of time course and dose of androgens in the inhibition of estrogen-induced sexual receptivity. Ovariectomized rats were treated with EB (2.0 microg per rat per day) for 6 days and tested for sexual receptivity (Test Day I). EB treatment continued for 15 days concomitant with daily administration of one of three doses of dihydrotestosterone propionate (DHTP; 7.5, 0.75, 0.075 mg/kg) or 3α-androstanediol (3α-Adiol; 3.75, 1.0, 0.375 mg/kg). Four tests for sexual receptivity were conducted on days 3, 6, 14, and 15 of the androgen/vehicle treatment period (Test Days II-V). On Day 15 (Test Day V), the rats received progesterone (1.0 mg per rat) 4 h before testing. Using the same experimental design, Experiment 2 examined the effect of increasing the dose of estrogen on the androgenic inhibition of sexual receptivity. Ovariectomized rats were treated with one of two doses of EB (2.0 or 10.0 microg per rat per day) concomitant with daily administration of DHTP (7.5 mg/kg) or 3α-Adiol (3.75 mg/kg). In Experiment 1, the highest doses of both DHTP and 3α-Adiol significantly inhibited estrogen-induced sexual receptivity. Data from Experiment 2 indicate that the inhibitory effects of DHTP but not 3α-Adiol can be moderated by an increased dose of EB.

Is a global rural and remote health research agenda desirable or is context supreme?

OBJECTIVE: This paper proposes that there is value in international comparison of rural and remote health-care service delivery models because of practical reasons - to find ideas, models and lessons to address 'local' delivery challenges; and for theoretical reasons - to derive a conceptual framework for international comparison. METHODS: Literature review and commentary. FINDINGS: There are significant challenges to international comparative research that have been highlighted generically; for example, equivalence of terminology, datasets and indicators. Context supremacy has been raised as a reason why models and research findings might not be transferable. This paper proposes that there is insufficient knowledge about how rural contexts in relation to health service delivery are similar or different internationally. Investigating contexts in different countries and identifying the dimensions on which service delivery might differ is an important stimulus for study. The paper suggests, for discussion, dimensions on which rural service delivery might differ between countries and regions, including physical geographical factors, social interaction with rurality, policies of service provision and the politics and operation of health care. CONCLUSIONS: The paper asks whether, given the need to develop models suitable for rural areas and for theory on rural health to extend, international comparative research is an imperative or an indulgence.