The Complete Sequence and Comparative Analysis of Ape Sex Chromosomes.

Apes possess two sex chromosomes-the male-specific Y and the X shared by males and females. The Y chromosome is crucial for male reproduction, with deletions linked to infertility. The X chromosome carries genes vital for reproduction and cognition. Variation in mating patterns and brain function among great apes suggests corresponding differences in their sex chromosome structure and evolution. However, due to their highly repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the state-of-the-art experimental and computational methods developed for the telomere-to-telomere (T2T) human genome, we produced gapless, complete assemblies of the X and Y chromosomes for five great apes (chimpanzee, bonobo, gorilla, Bornean and Sumatran orangutans) and a lesser ape, the siamang gibbon. These assemblies completely resolved ampliconic, palindromic, and satellite sequences, including the entire centromeres, allowing us to untangle the intricacies of ape sex chromosome evolution. We found that, compared to the X, ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements. This divergence on the Y arises from the accumulation of lineage-specific ampliconic regions and palindromes (which are shared more broadly among species on the X) and from the abundance of transposable elements and satellites (which have a lower representation on the X). Our analysis of Y chromosome genes revealed lineage-specific expansions of multi-copy gene families and signatures of purifying selection. In summary, the Y exhibits dynamic evolution, while the X is more stable. Finally, mapping short-read sequencing data from >100 great ape individuals revealed the patterns of diversity and selection on their sex chromosomes, demonstrating the utility of these reference assemblies for studies of great ape evolution. These complete sex chromosome assemblies are expected to further inform conservation genetics of nonhuman apes, all of which are endangered species.

Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

PET imaging of dopamine transporters and D2/D3 receptors in female monkeys: effects of chronic cocaine self-administration.

Brain imaging studies using positron emission tomography (PET) have shown that long-term cocaine use is associated with lower levels of dopamine (DA) D2/D3 receptors (D2/D3R); less consistent are the effects on DA transporter (DAT) availability. However, most studies have been conducted in male subjects (humans, monkeys, rodents). In this study, we used PET imaging in nine drug-naïve female cynomolgus monkeys to determine if baseline measures of DAT, with [18F]FECNT, and D2/D3R availability, with [11C]raclopride, in the caudate nucleus, putamen and ventral striatum were associated with rates of cocaine self-administration and if these measures changed during long-term (~13 months) cocaine self-administration and following time-off (3-9 months) from cocaine. Cocaine (0.2 mg/kg/injection) and 1.0 g food pellets were available under a multiple fixed-interval (FI) 3-min schedule of reinforcement. In contrast to what has been observed in male monkeys, baseline D2/D3R availability was positively correlated with rates of cocaine self-administration only during the first week of exposure; DAT availability did not correlate with cocaine self-administration. D2/D3R availability decreased ~20% following cumulative intakes of 100 and 1000 mg/kg cocaine; DAT availability did not significantly change. These reductions in D2/D3R availability did not recover over 9 months of time-off from cocaine. To determine if these reductions were reversible, three monkeys were implanted with osmotic pumps that delivered raclopride for 30 days. We found that chronic treatment with the D2/D3R antagonist raclopride increased D2/D3R availability in the ventral striatum but not in the other regions when compared to baseline levels. Over 13 months of self-administration, tolerance did not develop to the rate-decreasing effects of self-administered cocaine on food-reinforced responding, but number of injections and cocaine intake significantly increased over the 13 months. These data extend previous findings to female monkeys and suggest sex differences in the relationship between D2/D3R availability related to vulnerability and long-term cocaine use.

Foraging ecology of critically endangered Eastern Pacific hawksbill sea turtles (Eretmochelys imbricata) in the Gulf of California, Mexico.

The Eastern Pacific hawksbill sea turtle population is one of the most endangered of all sea turtle species. Here, we examine the foraging ecology of 47 hawksbill turtles (40.5-90.3 cm CCL, mean = 54.1 ± 10.1 cm) around Isla San José, Gulf of California, Mexico by integrating information from passive acoustic telemetry, behavior recordings, fecal analysis, and habitat surveys. Tagged hawkbill turtles exhibited high site fidelity over months and years (tracking duration 1-1490 days, mean = 255 ± 373 days) to the location and benthic habitat where individuals were initially caught. Diet was dominated by benthic invertebrates and algae including sponges, algae, tunicates, and mangrove roots. The mean percent cover of these benthic food items was significantly greater in the mangrove estuary than in adjacent rocky and sandy reef habitats. The Isla San José foraging ground is a high-use area for hawksbills and should be granted national protection status.

Field courses narrow demographic achievement gaps in ecology and evolutionary biology.

Disparities remain in the representation of marginalized students in STEM. Classroom-based experiential learning opportunities can increase student confidence and academic success; however, the effectiveness of extending learning to outdoor settings is unknown. Our objectives were to examine (a) demographic gaps in ecology and evolutionary biology (EEB) major completion, college graduation, and GPAs for students who did and did not enroll in field courses, (b) whether under-represented demographic groups were less likely to enroll in field courses, and (c) whether under-represented demographic groups were more likely to feel increased competency in science-related tasks (hereafter, self-efficacy) after participating in field courses. We compared the relationships among academic success measures and demographic data (race/ethnicity, socioeconomic status, first-generation, and gender) for UC Santa Cruz undergraduate students admitted between 2008 and 2019 who participated in field courses (N = 941 students) and who did not (N = 28,215 students). Additionally, we administered longitudinal surveys to evaluate self-efficacy gains during field-based versus classroom-based courses (N = 570 students). We found no differences in the proportion of students matriculating at the university as undecided, proposed EEB, or proposed other majors across demographic groups. However, five years later, under-represented students were significantly less likely to graduate with EEB degrees, indicating retention rather than recruitment drives disparities in representation. This retention gap is partly due to a lower rate of college completion and partly through attrition to other majors. Although under-represented students were less likely to enroll in field courses, field courses were associated with higher self-efficacy gains, higher college graduation rates, higher EEB major retention, and higher GPAs at graduation. All demographic groups experienced significant increases in self-efficacy during field-based but not lecture-based courses. Together, our findings suggest that increasing the number of field courses and actively facilitating access to students from under-represented groups can be a powerful tool for increasing STEM diversity.

Designing a mHealth clinical decision support system for Parkinson's disease: a theoretically grounded user needs approach.

BACKGROUND: Despite the established evidence and theoretical advances explaining human judgments under uncertainty, developments of mobile health (mHealth) Clinical Decision Support Systems (CDSS) have not explicitly applied the psychology of decision making to the study of user needs. We report on a user needs approach to develop a prototype of a mHealth CDSS for Parkinson's disease (PD), which is theoretically grounded in the psychological literature about expert decision making and judgement under uncertainty. METHODS: A suite of user needs studies was conducted in 4 European countries (Greece, Italy, Slovenia, the UK) prior to the development of PD_Manager, a mHealth-based CDSS designed for Parkinson's disease, using wireless technology. Study 1 undertook Hierarchical Task Analysis (HTA) including elicitation of user needs, cognitive demands and perceived risks/benefits (ethical considerations) associated with the proposed CDSS, through structured interviews of prescribing clinicians (N = 47). Study 2 carried out computational modelling of prescribing clinicians' (N = 12) decision strategies based on social judgment theory. Study 3 was a vignette study of prescribing clinicians' (N = 18) willingness to change treatment based on either self-reported symptoms data, devices-generated symptoms data or combinations of both. RESULTS: Study 1 indicated that system development should move away from the traditional silos of 'motor' and 'non-motor' symptom evaluations and suggest that presenting data on symptoms according to goal-based domains would be the most beneficial approach, the most important being patients' overall Quality of Life (QoL). The computational modelling in Study 2 extrapolated different factor combinations when making judgements about different questions. Study 3 indicated that the clinicians were equally likely to change the care plan based on information about the change in the patient's condition from the patient's self-report and the wearable devices. CONCLUSIONS: Based on our approach, we could formulate the following principles of mHealth design: 1) enabling shared decision making between the clinician, patient and the carer; 2) flexibility that accounts for diagnostic and treatment variation among clinicians; 3) monitoring of information integration from multiple sources. Our approach highlighted the central importance of the patient-clinician relationship in clinical decision making and the relevance of theoretical as opposed to algorithm (technology)-based modelling of human judgment.

Chronic Δ9-THC in Rhesus Monkeys: Effects on Cognitive Performance and Dopamine D2/D3 Receptor Availability.

Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of such deficits remain unclear. Adult male rhesus monkeys (N = 6) responded in the morning on tasks designed to assess different cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0.01-0.56 mg/kg, i.v.) on cognitive performance, FR responding, and body temperature were determined. Next, THC (1.0-2.0 mg/kg, s.c.) was administered daily after FR 10 sessions for 12 weeks, during which the residual effects of THC (i.e., 22 hours after administration) on cognition were examined and the acute effects of THC were redetermined. In a subgroup of monkeys, dopamine D2/D3 receptor availability was assessed after 4 weeks of chronic THC exposure and compared with drug-naive controls using positron emission tomography and [11C]-raclopride (N = 4/group). Acute THC pretreatments dose-dependently decreased FR responding and body temperature, and impairment to cognitive performance was task specific. During chronic treatment, THC produced persistent residual impairment only to working memory; tolerance differentially developed to acute cognitive impairments. There was recovery from residual cognitive impairments to working memory within 2 weeks of abstinence. Compared with controls, D2/D3 receptor availability was not altered during chronic THC treatment. In conclusion, THC-induced disruptions in cognition were task-specific, as was tolerance development, and not related to changes in D2/D3 receptor availability. Intervention strategies for cannabis-use disorder that enhance working memory performance may facilitate positive treatment outcomes.

Automated synthesis of 1-[11C]acetoacetate on a TRASIS AIO module.

We automated radiochemical synthesis of 1-[11C]acetoacetate in a commercially available radiochemistry module, TRASIS AllInOne by [11C]carboxylation of the corresponding enolate anion generated in situ from isopropenylacetate and MeLi, and purified by ion-exchange column resins.1-[11C]acetoacetate was synthesized with high radiochemical purity (95%) and specific activity (~ 66.6GBq/µmol, n = 30) with 35% radiochemical yield, decay corrected to end of synthesis. The total synthesis required ~ 16min. PET imaging studies were conducted with 1-[11C]acetoacetate in vervet monkeys to validate the radiochemical synthesis. Tissue uptake distribution was similar to that reported in humans.

Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

RATIONALE: Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. OBJECTIVE: In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. METHODS: Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [18F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. RESULTS: D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. CONCLUSIONS: These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months.

PURPOSE: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). METHODS: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. RESULTS: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p < 0.001), radiotherapy (p < 0.05), and reported poorer QoL (p = 0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p < 0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year CONCLUSIONS: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs.

The complete mitochondrial genome of the horned lizard Phrynosoma blainvillii (Squamata: Phrynosomatidae) from California, USA.

Analysis of Phrynosoma blainvillii Gray from Marina, Monterey County, California, using 150 bp paired-end Illumina sequences (Illumina, San Diego, CA) resulted in the assembly of its complete mitogenome. The mitogenome is 16,946 bp in length and contains a putative origin of light strand replication (OL), control region, 22 tRNA, 2 rRNA, and 13 protein-coding genes. Its content and organization are similar to other Squamata. Phylogenetic analysis of P. blainvillii resolves it in a clade with P. sherbrookei Nieto-Montes de Oca, Arenas-Moreno, Beltrán-Sánchez & Leaché, sister in position to Uma notata Baird. Mitochondrial marker analysis of P. blainvillii from Marina shows that it belongs to a coastal Santa Lucia Mountain Range haplogroup that is distinct from other populations of P. blainvillii in California.

Post-diagnostic dietary changes in prostate cancer: associations with patients' wellbeing and the perceptions of GPs.

This article aims to investigate associations between perceived control and health-related quality of life (HRQOL) with dietary changes after prostate cancer diagnosis and to explore General Practitioners' (GPs) perceptions on the role of diet in prostate cancer post-diagnosis. Ninety-five prostate cancer patients completed measures of dietary change, one for after diagnosis and another for after therapy. They also scored their HRQOL and perceived control. There were discrepancies in dietary changes reported between a general question (28.4% no dietary changes) and a specific (42.1%-51.5% range of no change for various food items). Most patients initiated healthy changes. Patients who changed their diet after diagnosis had lower cognitive functioning and external locus of control (doctors). Patients who changed their diet after therapy had lower cognitive and emotional functioning, quality of life and external locus of control (doctors). Then, fourty-four GPs responded to an online survey. Their open-ended responses were analysed using Content Analysis. They reported interest in the role of diet in cancer but also lack of relevant knowledge. They were skeptical on providing information. Clinical interventions should consider patients' cognitive ability, their relationship with their health professional and their wellbeing. Also, GPs' confidence to provide dietary advice needs to be addressed.

Risky sun tanning behaviours amongst Irish University students: a quantitative analysis.

BACKGROUND: Despite Ireland's temperate maritime climate, it has the third highest rate of malignant melanoma in the European Union, indicating the need to recognise tanning practices as a risky behaviour, especially amongst those most at risk (the younger population). AIM: To explore the factors associated with deliberate sun tanning amongst university students in Cork, Ireland. METHODS: Self-reported sun exposure, attitudes to tanning and sun protection practices were investigated using an online questionnaire in April 2010. RESULTS: There were 833 responses (8.33 %), mean age 22 years, 75 % female. Reporting deliberate tanning in the previous summer (n = 389, 46.7 %) was positively correlated (r = 0.622, p < 0.001) with stating an intention to tan next summer (n = 532, 63.9 %). Women and respondents with darker (vs. fairer) complexion were more likely to engage in deliberate tanning (p < 0.001). Deliberate tanning was associated with reporting enjoying tanning (p < 0.001), with reporting peer pressure into tanning (p = 0.039), and (marginally) with thinking it is worth getting burnt to get a tan (p = 0.068). Younger students were significantly more likely to report these attitudes; being a current smoker was associated with reporting peer pressure and that burning is worth a tan, indicating a level of risk-taking. Respondents reported (average) three sources of information on sun risks. CONCLUSION: Tanning is a form of strongly motivated risk-taking as much in a sun-limited country like Ireland as in hotter sun-rich climates. Risk communication strategies on sun exposure should be developed that target young people and improve their risk awareness.

Views of parents in four European countries about the effect of food on the mental performance of primary school children.

BACKGROUND/OBJECTIVES: Several factors affect the mental performance of children. The importance that parents attribute to food-related determinants, compared with genetic, socio-economic and school environment, was investigated. SUBJECTS/METHODS: Parents of school children (aged 4-11) were recruited through state primary schools in four European countries. Interviews were conducted in which participants were asked to sort 18 cards representing possible determinants of four elements of mental performance (attention, learning, mood and behaviour) according to perceived strength of effect. Determinants were identified from the literature and grouped in six categories: food-related, school environment, physical, social, psychological and biological. Effects were scored: 0=none; 1=moderate; and 2=strong. Views were compared between and within countries. RESULTS: Two hundred parents took part (England: 53; Germany: 45; Hungary: 52; Spain: 50). Differences existed between countries in the proportions reporting university education and being in employment. Taking all countries together, parents consider the food category (mean 1.33) to have a lower impact on a child's mental performance than physical (activity and sleep, 1.77), psychological (mood and behaviour, 1.69) and school environment (1.57). Social (1.12) and biological (0.91) determinants were ranked lower than food. Of determinants in the food category, parents thought regularity of meals had more influence on mental performance (1.58) than what a child eats now (1.36), food at school (1.35), nutrition as a baby/infant (1.02). CONCLUSION: Scope exists to improve parental awareness of the repercussions of their dietary choices for the mental performance of their children.

Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys.

RATIONALE: Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. OBJECTIVE: We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n = 5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n = 9). METHODS: Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and 4 days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. RESULTS: ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. CONCLUSIONS: The results indicate that repeated treatment with a low-efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity.

Patient-controlled sharing of medical imaging data across unaffiliated healthcare organizations.

BACKGROUND: Current image sharing is carried out by manual transportation of CDs by patients or organization-coordinated sharing networks. The former places a significant burden on patients and providers. The latter faces challenges to patient privacy. OBJECTIVE: To allow healthcare providers efficient access to medical imaging data acquired at other unaffiliated healthcare facilities while ensuring strong protection of patient privacy and minimizing burden on patients, providers, and the information technology infrastructure. METHODS: An image sharing framework is described that involves patients as an integral part of, and with full control of, the image sharing process. Central to this framework is the Patient Controlled Access-key REgistry (PCARE) which manages the access keys issued by image source facilities. When digitally signed by patients, the access keys are used by any requesting facility to retrieve the associated imaging data from the source facility. A centralized patient portal, called a PCARE patient control portal, allows patients to manage all the access keys in PCARE. RESULTS: A prototype of the PCARE framework has been developed by extending open-source technology. The results for feasibility, performance, and user assessments are encouraging and demonstrate the benefits of patient-controlled image sharing. DISCUSSION: The PCARE framework is effective in many important clinical cases of image sharing and can be used to integrate organization-coordinated sharing networks. The same framework can also be used to realize a longitudinal virtual electronic health record. CONCLUSION: The PCARE framework allows prior imaging data to be shared among unaffiliated healthcare facilities while protecting patient privacy with minimal burden on patients, providers, and infrastructure. A prototype has been implemented to demonstrate the feasibility and benefits of this approach.

Chronic treatment with extended release methylphenidate does not alter dopamine systems or increase vulnerability for cocaine self-administration: a study in nonhuman primates.

Despite the widespread use of stimulant medications for the treatment of attention deficit hyperactivity disorder, few studies have addressed their long-term effects on the developing brain or susceptibility to drug use in adolescence. Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N=8 per group). Doses were titrated to achieve initial drug blood serum levels within the therapeutic range in children and adjusted throughout the study to maintain target levels. Growth, including measures of crown-rump length and weight, was assessed before and after 1 year of treatment and after 3-5 months washout. In addition, positron emission tomography scans were performed to quantify binding availability of D2/D3 receptors and dopamine transporters (DATs). Distribution volume ratios were calculated to quantify binding of [¹8F]fluoroclebopride (DA D2/D3) and [¹8F]-(+)-N-(4-fluorobenzyl)-2ß-propanoyl-3ß-(4-chlorophenyl)tropane (DAT). Chronic MPH did not differentially alter the course of weight gain or other measures of growth, nor did it influence DAT or D2/D3 receptor availability after 1 year of treatment. However, after washout, the D2/D3 receptor availability of MPH-treated animals did not continue to decline at the same rate as control animals. Acquisition of intravenous cocaine self-administration was examined by first substituting saline for food reinforcement and then cocaine doses (0.001-0.1 mg/kg per injection) in ascending order. Each dose was available for at least five consecutive sessions. The lowest dose of cocaine that maintained response rates significantly higher than saline-contingent rates was operationally defined as acquisition of cocaine reinforcement. There were no differences in rates of acquisition, overall response rates, or cocaine intake as a function of cocaine dose between groups. In an animal model that closely mimics human development; chronic treatment with therapeutic doses of sustained release MPH did not have a significant influence on the regulation of DATs or D2/D3 receptors, or on standard measures of growth. Furthermore, this treatment regimen and subsequent drug washout did not have an impact on vulnerability to cocaine abuse.

Influences on infant feeding decisions of first-time mothers in five European countries.

BACKGROUND/OBJECTIVES: Infant feeding decisions made by new parents have significant health implications. The study aimed to investigate: influences on infant feeding decisions; characteristics of mothers reporting reliance on alternative information sources; associations between reliance on different sources and intentions to exclusively breastfeed and introduce complementary foods later; and subsequent breastfeeding and weaning behaviours. SUBJECTS/METHODS: First-time mothers in five European countries (England, Finland, Germany, Hungary, Spain) completed questionnaires about the importance of 17 influences on infant feeding choices at birth and 8 months later, during 2007-2008. Use of individual sources and reliance on four categories (family and friends, health professionals, written materials, audio-visual media) were compared between countries. Associations between information sources used and mother characteristics, feeding intentions and behaviours were investigated using appropriate statistical tests. RESULTS: In all, 2071 first-time mothers provided baseline data; 78% at 8 months. Variation exists between countries in the influence of different sources on feeding decisions of first-time mothers. Across all countries, the most important influences at both time points were books, partner and antenatal midwife. Mothers in higher income quintiles and remaining at school beyond age 16 years reported greater reliance on written sources (P<0.0005). Mothers relying most on written sources reported longer exclusive breastfeeding (P=0.002), and a tendency to introduce foods other than milk later (P=0.079) than mothers relying most on personal or professional contacts. CONCLUSION: Further research is required about which dissemination strategies are most effective at improving infant feeding behaviours in varied cultural settings, and for different socio-economic groups.

Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in Rhesus monkeys.

BACKGROUND: Chronic cocaine use is associated with neurobiological and cognitive deficits that persist into abstinence, hindering success of behavioral treatment strategies and perhaps increasing likelihood of relapse. The effects of current cocaine use and abstinence on neurobiology and cognition are not well characterized. METHODS: Adult male rhesus monkeys with an extensive cocaine self-administration history (∼ 5 years) and age-matched control animals (n = 4/group) performed cognitive tasks in morning sessions and self-administered cocaine or food in afternoon sessions. Positron emission tomography and [(18)F]-fluorodeoxyglucose were employed to assess cerebral metabolic rates of glucose utilization during cognitive testing. RESULTS: Cocaine-experienced monkeys required significantly more trials and committed more errors on reversal learning and multidimensional discriminations, compared with control animals. Cocaine-naive, but not cocaine-experienced, monkeys showed greater metabolic rates of glucose utilization during a multidimensional discrimination task in the caudate nucleus, hippocampus, anterior and posterior cingulate, and regions associated with attention, error detection, memory, and reward. Using a delayed match-to-sample task, there were no differences in baseline working memory performance between groups. High-dose cocaine self-administration disrupted delayed match-to-sample performance but tolerance developed. Acute abstinence from cocaine did not affect performance, but by day 30 of abstinence, accuracy increased significantly, while performance of cocaine-naive monkeys was unchanged. CONCLUSIONS: These data document direct effects of cocaine self-administration on cognition and neurobiological sequelae underlying cognitive deficits. Improvements in working memory can occur in abstinence, albeit across an extended period critical for treatment seekers, suggesting pharmacotherapies designed to enhance cognition may improve success of current behavioral modification strategies.

Social dominance in female monkeys: dopamine receptor function and cocaine reinforcement.

BACKGROUND: Brain imaging and behavioral studies suggest an inverse relationship between dopamine (DA) D2/D3 receptors and vulnerability to cocaine abuse, although most research has used males. For example, male monkeys that become dominant in a social group have significant elevations in D2/D3 receptor availability and are less vulnerable to cocaine reinforcement. METHODS: DA D2/D3 receptor availability was assessed in female cynomolgus monkeys (n = 16) with positron emission tomography (PET) while they were individually housed, 3 months after stable social hierarchies had formed, and again when individually housed. In addition, PET was used to examine changes in dopamine transporter (DAT) availability after social hierarchy formation. After imaging studies were complete, monkeys received implantation with indwelling intravenous catheters and self-administered cocaine (.001-.1 mg/kg/injection) under a fixed-ratio 30 schedule of reinforcement. Acquisition of cocaine reinforcement occurred when response rates were significantly higher than when saline was self-administered. RESULTS: Neither DAT nor D2/D3 receptor availability in the caudate nucleus and putamen was predictive of social rank, but both significantly changed after formation of social hierarchies. DA D2/D3 receptor availability significantly increased in females that became dominant, whereas DAT availability decreased in subordinate females. Dominant female monkeys acquired cocaine reinforcement at significantly lower doses than subordinate monkeys. CONCLUSIONS: The relationship between D2/D3 receptor availability and vulnerability to cocaine reinforcement seems, on the basis of these findings, opposite in females and males. These data indicate that the social environment profoundly affects the DA system but does so in ways that have different functional consequences for females than for males.