Serotonergic innervation of the amygdala is increased in autism spectrum disorder and decreased in Williams syndrome.

BACKGROUND: Williams syndrome (WS) and autism spectrum disorder (ASD) are neurodevelopmental disorders that demonstrate overlapping genetic associations, dichotomous sociobehavioral phenotypes, and dichotomous pathological differences in neuronal distribution in key social brain areas, including the prefrontal cortex and the amygdala. The serotonergic system is critical to many processes underlying neurodevelopment and is additionally an important neuromodulator associated with behavioral variation. The amygdala is heavily innervated by serotonergic projections, suggesting that the serotonergic system is a significant mediator of neuronal activity. Disruptions to the serotonergic system, and atypical structure and function of the amygdala, are implicated in both WS and ASD. METHODS: We quantified the serotonergic axon density in the four major subdivisions of the amygdala in the postmortem brains of individuals diagnosed with ASD and WS and neurotypical (NT) brains. RESULTS: We found opposing directions of change in serotonergic innervation in the two disorders, with ASD displaying an increase in serotonergic axons compared to NT and WS displaying a decrease. Significant differences (p < 0.05) were observed between WS and ASD data sets across multiple amygdala nuclei. LIMITATIONS: This study is limited by the availability of human postmortem tissue. Small sample size is an unavoidable limitation of most postmortem human brain research and particularly postmortem research in rare disorders. CONCLUSIONS: Differential alterations to serotonergic innervation of the amygdala may contribute to differences in sociobehavioral phenotype in WS and ASD. These findings will inform future work identifying targets for future therapeutics in these and other disorders characterized by atypical social behavior.

Motility of actin filaments on micro-contact printed myosin patterns.

Protein molecular motors, which convert, directly and efficiently, chemical energy into motion, are excellent candidates for integration in hybrid dynamic nanodevices. To integrate and use the full potential of molecular motors in these devices, their design requires a quantitative and precise prediction of the fundamental mechanical and physicochemical features of cytoskeletal proteins operating in artificial environments. In that regard, the behavior of protein molecular motors constructs in/on nano-confined spaces or nanostructured surfaces that aim to control their motility is of critical interest. Here, we used a standard gliding motility assay to study the actin filaments sliding on a surface comprising heavy mero myosin (HMM) micro- and nano-patterns. To print HMM, we used negative tone, micro contact printing of a blocking protein (bovine serum albumin, BSA) on a nitrocellulose surface, followed by specific adsorption of HMM on BSA-free surfaces. While the large BSA-free patterns allowed for selective confinement of actin filaments motility, the BSA-stamped areas displayed intricate nano-sized HMM patterns, which enabled a deeper analysis of the nano-mechanics of actomyosin motility in confined spaces.

Physician credentials and practices associated with childhood immunization rates: private practice pediatricians serving poor children in New York City.

Private practice physicians in New York City's poorest neighborhoods are typically foreign trained, have generally substandard clinical practices, and have been accused of rushing Medicaid patients through to turn a profit. However, they also represent a sizable share of physician capacity in medically underserved neighborhoods. This article documents the level of credentials, systems, and immunization-related procedures among these physicians. Furthermore, it assesses the relationship between such characteristics and childhood immunization rates. The analysis utilizes a cross-sectional comparison of immunization rates in 60 private practices that submitted 2,500 or more Medicaid claims for children. Immunization data were gathered from medical records for 2,948 randomly selected children under 3 years of age. Half of sampled physicians were board certified (55%), and half were accepted by the Medicaid Preferred Physicians and Children (PPAC) program (51.7%). Of physicians, 43% saw patients only on a walk-in basis, while only 17% scheduled the next appointment while the patient was still in the office. There were 75% of the physicians who reported usually immunizing at acute care visits. Immunization rates were higher among PPAC physicians compared to others (41% vs. 29% up to date for diphtheria and tetanus toxoids and pertussis [DTP]/Haemophilus influenzae type b [Hib], polio, and measles-mumps-rubella [MMR], P = .01), and board-certified physicians showed a trend toward better immunization rates (39% vs. 30%, P =.07). Physicians who reported usually immunizing at acute care visits also had higher rates than those who did not (38% vs. 27%, P = .05). Scheduling a date and time for the next immunization showed a trend toward association with immunization coverage (37% vs. 28%, P= .10). Private practice physicians who provide high volumes of care reimbursed by Medicaid have improved their credentials and affiliations over time, thereby expanding reimbursement options. Credentials and affiliations were at least as effective in distinguishing relatively high- and low-performing physicians, as were immunization-related practices, suggesting that they are useful markers for higher quality care. The relative success of the PPAC program should inform efforts to improve the capacity and quality of primary care for vulnerable children. Appointment and reminder systems that effectively manage the flow of children back into the office for immunizations and the vigilant use of acute care visits for immunizations go hand in hand. Opportunity exists for payers and plans to encourage and support these actions.

Evaluation of an automated liquid-handling system (Tecan Genesis RSP 100) in the Abbott LCx assay for Chlamydia trachomatis.

The present study investigated the feasibility of automating the specimen-pipetting component of sample preparation in the LCx Chlamydia assay (LCx-CT assay; Abbott Laboratories, Chicago, Ill.) by using a commercially available liquid-handling system (Tecan Genesis RSP100; Tecan Inc., Research Triangle Park, N.C.). The Tecan instrument proved to be comparable in both precision and accuracy to a manual multipipettor (Eppendorf model 4850; Eppendorf Scientific, Westbury, N.Y.). The Tecan instrument was extensively checked for evidence of specimen-to-specimen transfer, and no level of contamination sufficient to generate a signal above the background in the LCx-CT assay was detected. Finally, pipetting speed was significantly improved by using the Tecan instrument. A mean time of 2.5 min was required to pipette a complete LCx-CT assay carousel (20 samples and 4 controls) with the Tecan instrument, whereas 8.4 min was required to pipette a comparable number of samples manually (P < 0.001).

Patterns of insurance coverage within families with children.

This paper examines patterns of health insurance within families with children, using the 1996 Medical Expenditure Panel Survey (MEPS). Four and a half million families (14 percent) had insurance for some, but not all, family members. These partially insured families generally obtained coverage because of one of three situations: (1) A parent earned relatively higher wages and received the concomitant benefits of such jobs but could not afford dependent coverage; (2) the family had young children who were covered by Medicaid through more generous eligibility thresholds for children under age six, while other family members were ineligible; or (3) the family had a member who was eligible for public coverage because of a disability. Each of these situations offers the platform from which incremental policies might efficiently expand coverage to families.

Use of an enzyme immunoassay does not eliminate the need to analyze multiple stool specimens for sensitive detection of Giardia lamblia.

The relative sensitivities of a commercially available enzyme immunoassay (EIA) (ProSpecT Giardia; Alexon-Trend Inc., Ramsey, Minn.) and conventional ovum-and-parasite (O&P) examination for the detection of Giardia lamblia in preserved stool specimens were determined. Paired stool samples collected independently within a 7-day period from 103 patients were analyzed by both methods. A total of 54 specimens from 30 patients (18 asymptomatically infected with G. lamblia and 12 with symptoms consistent with intestinal giardiasis) were determined to be positive for G. lamblia, of which 48 (88.9%) were positive by microscopy and 52 (96.3%) were positive by EIA. Both specimens submitted were positive for G. lamblia by O&P examination for 66.7% (20 of 30) of the positive patients; for 26.7% (8 of 30) a single specimen was positive by O&P examination, and for 6.7% (2 of 30) of those determined to be infected with G. lamblia, both samples were negative by microscopy. The sensitivity of conventional O&P examination was somewhat higher in symptomatically infected individuals, with 75% (9 of 12) of patients in this category having G. lamblia detected in both samples, compared with 61% (11 of 18) of asymptomatic patients. A total of 24 positive patients (80%) had G. lamblia antigen detected by EIA in both submitted samples, 4 positive patients (13.3%) had one specimen positive by EIA, and the EIA was negative in both specimens from 2 infected individuals (6.5%), the sensitivity of EIA was substantially equivalent in asymptomatic and symptomatic individuals (77 versus 83% of patients with positive results on both specimens). Although the sensitivity of EIA for the detection of G. lamblia on a single stool specimen was somewhat higher than that of conventional O&P examination in symptomatic patients (83 versus 75%), in asymptomatic patients (77 versus 61%), and overall (80 versus 67%), examination of two specimens by either EIA or microscopy was necessary to achieve a diagnostic sensitivity of greater than 90%.

Comparison of preventive care in Medicaid managed care and Medicaid fee for service in institutions and private practices.

OBJECTIVE: To compare preventive screening for children in Medicaid managed care (MMC) with children in Medicaid fee for service (M-FFS) in private and institutional settings. METHODS: The sample included randomly selected institutions and private practice physicians in New York City. Within setting, children in MMC and M-FFS were sampled randomly and charts reviewed for immunizations and lead and anemia screening. RESULTS: In both institutions and private practices, children enrolled in MMC appeared more likely to be up-to-date than their M-FFS counterparts for immunizations (institution, P <.01; private practice, P <.05), lead screening (institution, P <.01; private practice, P <.01), and anemia screening (institution, P <.01; private practice, P <.01). However, children in MMC had more visits (P <.01) and were followed up for a longer time (P <.01). After controlling for these variables, effects of MMC diminished and only remained significant for screening among private physicians. When considering 10 different attributes of managed care plans, no clear pattern of association with better preventive care services was observed. CONCLUSION: The positive effect of managed care on preventive care services was largely explained by more visits and longer follow-up time; however, there were differences between institutions and private practices, with enrollment in MMC associated with some positive effect on screenings in private practices.

Effects of tryptophan loading on verbal, spatial and affective working memory functions in healthy adults.

Serotonin (5-HT) appears to modulate affective behaviours by providing a homeostatic threshold around which other transmitters respond. This general principle of activity should hold for other types of behaviour, including cognition, but has not been extensively examined. We hypothesized, based on past findings, that increased 5-HT would constrain prefrontally guided working memory functions that are mediated by catecholamine neurotransmitters. Healthy adults ingested amino acid compounds designed to deplete and load systemic tryptophan levels in a repeated-measures crossover design. Outcome variables included total plasma tryptophan, serum prolactin levels and self-report measures of mood, as well as measures of motor skill, attention, memory span and working memory for verbal, spatial and affective stimuli. Our findings indicate decrements in working memory for verbal and affective stimuli following tryptophan loading versus depletion, as well as subtle changes in vigilant attention and motor coordination. Implications for the aetiology and treatment of affective disorders and psychosis are discussed.

Performance of para-Pak Ultra ECOFIX compared with Para-Pak Ultra formalin/mercuric chloride-based polyvinyl alcohol for concentration and permanent stained smears of stool parasites.

ECOFIX is a mercury and formalin-free fecal preservative that can be used for concentration of stool specimens and preparation of permanently-stained slides. In this study, the standard two-vial ParaPak Ultra system was compared with ECOFIX Ultra for the detection of intestinal parasites. A total of 261 specimens in 92 sets (77 with 3 specimens, 15 with 2 specimens) were collected in ECOFIX, formalin, and low viscosity polyvinyl alcohol (LV-PVA). Concentrations were performed from ECOFIX using Hemo-De and saline and from formalin using ethyl acetate and formalin. To prepare permanently-stained smears, ECOSTAIN (a modification of Wheatley's trichrome stain) was used on ECOFIX material and Wheatley's trichrome stain was used on specimens preserved in PVA. A total of 157 protozoa and helminths were detected; 132 (84.1%) were recovered in formalin/PVA and 129 (82.2%) in ECOFIX. In permanently-stained smears, 139 protozoa were observed, 116 (83.5%) in PVA-preserved material and 117 (84.2%) in ECOFIX. Fecal concentration yielded 111 parasites (103 protozoa and 8 helminths), of which 98 (88.3%) were detected in formalin-fixed stool and 48 (43.2%) in ECOFIX. Significantly fewer ECOFIX-preserved concentrates were positive for Blastocystis hominis (35 versus 15, p-value <0.001) and Endolimax nana (19 versus 2, p-value <0.001). In conclusion, use of the ECOFIX Ultra collection device in combination with ECOSTAIN resulted in largely comparable recovery of enteric parasites to the conventional two-vial ParaPak Ultra system when both sedimentation-concentration and permanently stained smears were performed, and 2-3 specimens per patient were evaluated.

Individual differences predictive of drinking to manage anxiety among non-problem drinkers with panic disorder.

BACKGROUND: Alcohol problems co-occur with anxiety disorders at a rate that far exceeds chance ("comorbidity"). One view suggests that risk for developing a comorbid alcohol use disorder is increased when alcohol is used routinely to cope with anxiety symptoms ("self-medication"). Indicating that this view is overly broad, however, the literature suggests that only a subgroup of anxiety-disordered individuals tend to drink to manage their symptoms. Therefore, we set out to identify psychological characteristics that might mark those for whom drinking to cope with anxiety is most likely. Our survey of the literature identified several possibilities, including anxiety-related personality traits (anxiety sensitivity, self-consciousness and Trait Anxiety); higher-order personality dimensions (Harm Avoidance, Reward Dependence, and Novelty Seeking); and, finally, alcohol outcome expectancies (specifically, those related to tension-reducing effects from alcohol). METHODS: In a sample of nonproblem drinkers with panic disorder, we regressed predictor variables on several alcohol use measures, including drinking aimed at the control of anxiety symptoms ("self-medication"). RESULTS: Although each variable related positively to a self-medicating style of drinking, expectancies for tension reduction from alcohol use accounted for about twice as much variance as did the other predictors. With simultaneous entry in a step-wise regression analysis, only tension-reduction alcohol outcome expectancies and the Harm Avoidance personality dimension were retained as significant predictors. CONCLUSIONS: Findings suggest that development of a self-medicating style of drinking among individuals with panic disorder is predicated, in part, on specific psychological characteristics of the individual. Alcohol outcome expectancies emerged as the single most important predictor of drinking behavior in this anxiety-disordered sample.

The impact of physician bonuses, enhanced fees, and feedback on childhood immunization coverage rates.

OBJECTIVES: The purpose of this study was to examine the effects on immunization coverage of 3 incentives for physicians--a cash bonus for practice--wide increases, enhanced fee for service, and feedback. METHODS: Incentives were applied at 4-month intervals over 1 year among 60 inner-city office-based pediatricians. At each interval, charts of 50 randomly selected children between 3 and 35 months of age were reviewed per physician. RESULTS: The percentage of children who were up to date for diphtheria, tetanus, and pertussis and Haemophilus influenzae type b; polio; and measles-mumps-rubella immunization in the study's bonus group improved by 25.3 percentage points (P < .01). No significant changes occurred in the other groups. However, percentage of immunizations received outside the participating practice also increased significantly in the bonus group (P < .01). Levels of missed opportunities to immunize were high in all groups and did not change over time. Physicians' knowledge of contraindications was low. CONCLUSIONS: Bonuses sharply and rapidly increased immunization cover-age in medical records. However, much of the increase was the result of better documentation. A bonus is a powerful incentive, but more structure or education may be necessary to achieve the desired results.

Comparison of simple and rapid methods for identifying enterococci intrinsically resistant to vancomycin.

Three different methodologies, reduction of litmus milk (LM) and acidification of arabinose (ARA), acidification of methyl-alpha-D-glucopyranoside (MGP), and rapid motility (RM), for differentiating isolates of Enterococcus casseliflavus and Enterococcus gallinarum (intrinsically vancomycin-resistant enterococci [IVRE]) from Enterococcus faecalis and Enterococcus faecium were evaluated. All 33 isolates of E. faecalis tested reduced LM within 4 h and were negative in all other tests, while the 53 isolates of E. faecium were ARA positive only. In contrast, 45 of 46 (98%) IVRE isolates examined (26 E. casseliflavus and 20 E. gallinarum isolates) acidified MGP, 41 of 46 (89%) were LM and ARA positive, and 45 of 46 (98%) were RM positive. Acidification of MGP was therefore the single most useful test for differentiating IVRE from vancomycin-resistant E. faecium and E. faecalis; however, a combination of LM-ARA and RM testing enabled the correct designation of organisms without the need for overnight incubation.

Is insurance for children enough? The link between parents' and children's health care use revisited.

Parents' own use of physician services is known to be a strong predictor of their children's use of such services. This paper contrasts the relationship between parents' and children's use of services among uninsured and privately insured children. Parents' utilization is found to have a larger impact upon service use among privately insured children than among uninsured children. Even if all children were universally insured, parents' health care utilization would remain a key determinant in children's use of services. Policies that integrate financing and delivery systems for all family members deserve attention among efforts to foster better access for children. Neglecting financial access to care for adults may have the unintended effect of diminishing the impact of targeted health insurance programs for children.

The transition from Medicaid fee-for-service to managed care among private practitioners in New York City: effect on immunization and screening rates.

OBJECTIVES: This study examined the association between participation in Medicaid managed care and up-to-date coverage for childhood immunizations and screenings among private practice physicians serving New York City's poorest neighborhoods. METHOD: A random sample of 2174 children 3-35 months of age was drawn from 60 physician practices in 1995, and a cross-sectional analysis was used to compare up-to-date status for immunizations, and lead and anemia screening tests, for children cared for by managed care and nonmanaged care physicians. In 1996, an independent sample of 2380 children from the same practices was used to compare up-to-date status for individual children enrolled in Medicaid managed care and children predominantly enrolled in traditional fee-for-service Medicaid. Information from physician interviews augmented chart review data. Chi-square analysis and logistic regression were used. RESULTS: Physicians who participate in Medicaid managed care and those who do not had equal up-to-date coverage for immunizations (41.0 vs. 36.9%, p = .527), and lead (46.8 vs. 38.7%, p = .199) and anemia screening (63.2 vs. 56.5%, p = .272). Measures of the process of care were also similar for the two groups of physicians. Children themselves enrolled in Medicaid managed care appeared significantly more likely to be up-to-date than their nonmanaged care counterparts for immunizations (OR = 1.53, p = .027) and anemia screening (OR = 2.95, p = .000). CONCLUSIONS: Participation in managed care does not seem to change physicians' overall preventive care practice behavior. Available data did not reveal major differences in demographics or health status between individual children enrolled in managed care and those not enrolled. That children enrolled in managed care were better immunized and screened than those in fee-for-service Medicaid suggests that physicians receiving compensation under two payment systems may treat children differently depending on each child's mode of reimbursement.

Effect of the vaccines for children program on inner-city neighborhood physicians.

OBJECTIVE: To determine the probable effect of the Vaccines for Children (VFC) program on immunization coverage. DESIGN: Preintervention and postintervention study design, with data collected before and after enrollment in the VFC program. SETTING: Twenty-three inner-city neighborhood physicians' offices in New York City. PARTICIPANTS: In 1993, 30 physicians were randomly selected from 8 neighborhoods with the highest proportions of Medicaid-eligible individuals in New York City. In 1995-1996, the 30 physicians were contacted again. Twenty-three agreed to an interview and medical record review. Within each office, the medical records of children aged 3 to 35 months, with at least 3 visits in a 3-month or longer period, were randomly selected. Medical record reviews were conducted for 173 eligible children in 1993 and 528 in 1995-1996. INTERVENTIONS: The VFC program was implemented in October 1994. The administration fee increased from $2 to $17.85; physicians received vaccines free. MAIN OUTCOME MEASURES: Up-to-date status for immunizations and lead and tuberculosis screening; percentage of visits that are missed opportunities to immunize; and percentage of visits that were well-child visits. Up-to-date status, missed opportunities to immunize, and well-child visits were compared across time using chi 2 analysis, corrected for the use of cluster sampling. RESULTS: Up-to-date status changed significantly before and alter enrollment in the VFC program (P < .05) for all immunizations and for lead and tuberculosis screening. For the diphtheria toxoid, tetanus toxoid, and pertussis vaccine, oral poliovirus vaccine, and measles, mumps, and rubella vaccine combined, coverage increased from 17.9% to 42.2%, up by 24.3 percentage points (P < .05). Missed opportunities to immunize did not change, but well-child visits increased from 15.0% to 21.6% (P < .05). Physicians generally attributed performance improvements to the VFC program and not to other competing hypotheses. CONCLUSIONS: The VFC program seems to be responsible for an increase in immunization rates among these physicians.

Consistent fractionation of 13C in nature and in the laboratory: growth-rate effects in some haptophyte algae.

The carbon isotopic fractionation accompanying formation of biomass by alkenone-producing algae in natural marine environments varies systematically with the concentration of dissolved phosphate. Specifically, if the fractionation is expressed by epsilon p approximately delta e - delta p, where delta e and delta p are the delta 13C values for dissolved CO2 and for algal biomass (determined by isotopic analysis of C37 alkadienones), respectively, and if Ce is the concentration of dissolved CO2, micromole kg-1, then b = 38 + 160*[PO4], where [PO4] is the concentration of dissolved phosphate, microM, and b = (25 - epsilon p)Ce. The correlation found between b and [PO4] is due to effects linking nutrient levels to growth rates and cellular carbon budgets for alkenone-containing algae, most likely by trace-metal limitations on algal growth. The relationship reported here is characteristic of 39 samples (r2 = 0.95) from the Santa Monica Basin (six different times during the annual cycle), the equatorial Pacific (boreal spring and fall cruises as well as during an iron-enrichment experiment), and the Peru upwelling zone. Points representative of samples from the Sargasso Sea ([PO4] < or = 0.1 microM) fall above the b = f[PO4] line. Analysis of correlations expected between mu (growth rate), epsilon p, and Ce shows that, for our entire data set, most variations in epsilon p result from variations in mu rather than Ce. Accordingly, before concentrations of dissolved CO2 can be estimated from isotopic fractionations, some means of accounting for variations in growth rate must be found, perhaps by drawing on relationships between [PO4] and Cd/Ca ratios in shells of planktonic foraminifera.

Medicaid managed care in New York: problems and promise for childhood immunizations.

New York State is aggressively pursuing mandatory Medicaid managed care. Under managed care, physicians and plans have a defined population for which they are responsible, quality assurance monitoring emphasizes immunization rates along with other preventive services, and population-based incentives are possible. The literature does not offer compelling evidence, however, that immunization coverage is any better in managed care than under fee-for-service. If reimbursement is low and physician capacity insufficient, immunization rates may be considerably worse. In New York, care needs to be taken so that expansion does not outstrip the capacity of managed care plans to absorb additional enrollees.

Management techniques at primary care health centers: the impact of management innovation.

Long-term financial viability was a goal of The Program to Strengthen Primary Care Health Centers. To accomplish this, it was expected that participant centers would increase their management capabilities. We evaluated 32 management techniques in five principal areas: budgeting, strategic planning, general financial management, collections, and general health services management. Eight of the techniques showed change over the course of the demonstration (six increases and two decreases). It appears that there was somewhat more improvement among study centers than in a comparison group. Management sophistication has been expanding among health centers in general; Program participation appears to have accelerated this growth.

Implementation of management innovation at primary care health centers: qualitative assessments.

This article describes the implementation of innovations at health centers participating in The Robert Wood Johnson Foundation Program to Strengthen Primary Care Health Centers. Relatively successful approaches to management innovation are described and common obstacles to innovation are considered. Key issues include poor physician retention, inadequate or inappropriate space, the complexities of automation, difficulty in the recruitment of staff and consultants (particularly in rural areas), and disruptions caused by internal promotions.

Case studies of management innovation at primary care health centers.

This article discusses the experiences of four individual health centers that participated in The Program to Strengthen Primary Care Health Centers. These centers were attempting "typical" initiatives, were considered highly likely to succeed, and were located in geographically diverse areas. Given these characteristics, it is likely that other centers could replicate their endeavors and could gain valuable knowledge from their implementation experiences. This article presents each center's characteristics, history, and mission; describes the environment in which the center operates; and discusses the barriers to implementation of selected innovations.