Synaptotagmins 1 and 7 in vesicle release from rods of mouse retina.

Synaptotagmins are the primary Ca2+ sensors for synaptic exocytosis. Previous work suggested synaptotagmin-1 (Syt1) mediates evoked vesicle release from cone photoreceptor cells in the vertebrate retina whereas release from rods may involve another sensor in addition to Syt1. We found immunohistochemical evidence for syntaptotagmin-7 (Syt7) in mouse rod terminals and so performed electroretinograms (ERG) and single-cell recordings using mice in which Syt1 and/or Syt7 were conditionally removed from rods and/or cones. Synaptic release was measured in mouse rods by recording presynaptic anion currents activated during glutamate re-uptake and from exocytotic membrane capacitance changes. Deleting Syt1 from rods reduced glutamate release evoked by short depolarizing steps but not long steps whereas deleting Syt7 from rods reduced release evoked by long but not short steps. Deleting both sensors completely abolished depolarization-evoked release from rods. Effects of various intracellular Ca2+ buffers showed that Syt1-mediated release from rods involves vesicles close to ribbon-associated Ca2+ channels whereas Syt7-mediated release evoked by longer steps involves more distant release sites. Spontaneous release from rods was unaffected by eliminating Syt7. While whole animal knockout of Syt7 slightly reduced ERG b-waves and oscillatory potentials, selective elimination of Syt7 from rods had no effect on ERGs. Furthermore, eliminating Syt1 from rods and cones abolished ERG b-waves and additional elimination of Syt7 had no further effect. These results show that while Syt7 contributes to slow non-ribbon release from rods, Syt1 is the principal sensor shaping rod and cone inputs to bipolar cells in response to light flashes.

Local Adaptation in Marine Foundation Species at Microgeographic Scales.

AbstractNearshore foundation species in coastal and estuarine systems (e.g., salt marsh grasses, mangroves, seagrasses, corals) drive the ecological functions of ecosystems and entire biomes by creating physical structure that alters local abiotic conditions and influences species interactions and composition. The resilience of foundation species and the ecosystem functions they provide depends on their phenotypic and genetic responses to spatial and temporal shifts in environmental conditions. In this review, we explore what is known about the causes and consequences of adaptive genetic differentiation in marine foundation species over spatial scales shorter than dispersal capabilities (i.e., microgeographic scales). We describe the strength of coupling field and laboratory experiments with population genetic techniques to illuminate patterns of local adaptation, and we illustrate this approach by using several foundation species. Among the major themes that emerge from our review include (1) adaptive differentiation of marine foundation species repeatedly evolves along vertical (i.e., elevation or depth) gradients, and (2) mating system and phenology may facilitate this differentiation. Microgeographic adaptation is an understudied mechanism potentially underpinning the resilience of many sessile marine species, and this evolutionary mechanism likely has particularly important consequences for the ecosystem functions provided by foundation species.

Impact of corset bracing on 3D spine kinematics during ADL in children with Spondylolysis.

Spondylolysis is a stress fracture of the vertebral pars interarticularis that frequently affects adolescents involved in sports. Conservative bracing methods may assist the clinician in treating spondylolysis, though there is a need to further validate these techniques. The goal of this study was to evaluate differences in the 3D movements of the thoracic and lumbar spine before and after bracing. Five patients (mean age 14.4 ± 1.3 years) with spondylogenic back pain were evaluated for kinematic measurements using a Vicon motion capture system. Patients performed activities both with and without a lumbar corset brace including walking, kneeling, standing from a chair, standing from the floor, ascending and descending stairs, and lifting. Patients were evaluated for differences in thoracic and lumbar range of motion (ROM) in the braced and unbraced condition. While wearing the brace, patients demonstrated reduced extension ROM of the thoracic spine while walking (mean reduction = 0.4°), ascending stairs (3.0°), descending stairs (2.1°), lifting (14.8°), standing from a chair (4.1°), standing from the floor (16.7°), and kneeling (8.4°). Patients also exhibited reduced extension ROM of the total lumbar spine while ascending stairs (mean reduction = 1.8°), lifting (12.7°), standing from a chair (9.5°), standing from the floor (11.8°), and kneeling (4.7°). These results provide evidence that bracing reduces stress on the pars interarticularis and relieves symptoms in the athlete with spondylogenic back pain, thereby facilitating a return to sports.

Demonstration of the herd effect in adults after the implementation of pneumococcal vaccination with PCV13 in children.

The purpose of this investigation was to describe the evolution of serotypes and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from both adults and children from the same population area with invasive pneumococcal disease (IPD) or acute otitis media (AOM), 5 years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). From 2009 to 2015, 839 strains of S. pneumoniae strains were collected (481 from adults and 358 from children). Serotyping by latex antisera and molecular methods was performed. Antimicrobial susceptibility was tested. Compared to 2009, the total number of strains isolated in 2015 decreased in children (263 vs. 53, respectively) and in adults (220 vs. 131, respectively). Serotype coverage of PCV13 for IPD decreased significantly in adults from 67.7% (149/220) to 25.2% (33/131) and in children from 75.1% (61/81) to 18.5% (5/27). Especially, serotypes 1, 7F and 19A decreased significantly in children, while serotypes 7F and 19A decreased significantly in adults. PCV13 serotypes involved in AOM decreased significantly over the 5-year period, from 85.7% (156/182) to 38.5% (10/26), and were more susceptible to penicillin, amoxicillin and cefotaxime, p < 0.05. Serotypes 8, 9N and 10A seemed to emerge in adults, whereas any serotype prevalence was observed in children. Between 2009 and 2015, the introduction of PCV13 has resulted in a significant decrease of the number of S. pneumoniae strains isolated from IPD in children as in adults. It highlights a strong herd effect of vaccination in adults.

Currents connecting communities: nearshore community similarity and ocean circulation.

Understanding the mechanisms that create spatial heterogeneity in species distributions is fundamental to ecology. For nearshore marine systems, most species have a pelagic larval stage where dispersal is strongly influenced by patterns of ocean circulation. Concomitantly, nearshore habitats and the local environment are also influenced by ocean circulation. Because of the shared dependence on the seascape, distinguishing the relative importance of the local environment from regional patterns of dispersal for community structure remains a challenge. Here, we quantify the "oceanographic distance" and "oceanographic asymmetry" between nearshore sites using ocean circulation modeling results. These novel metrics quantify spatial separation based on realistic patterns of ocean circulation, and we explore their explanatory power for intertidal and subtidal community similarity in the Southern California Bight. We find that these metrics show significant correspondence with patterns of community similarity and that their combined explanatory power exceeds that of the thermal structure of the domain. Our approach identifies the unique influence of ocean circulation on community structure and provides evidence for oceanographically mediated dispersal limitation in nearshore marine communities.

Early and periodic screening, diagnosis, and treatment examination completion rates for Oklahoma Medicaid managed care: 1995-1998.

Although quality medical care is a goal of all health care providers, finding a means by which to take that idea from the abstract to the measurable is often an arduous task. The Oklahoma Health Care Authority and the Oklahoma Foundation for Medical Quality confronted that challenge when examining the state of Oklahoma's Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) examination completion rates. Focused on measuring processes of care, the Oklahoma Health Care Authority (OHCA) and the Oklahoma Foundation for Medical Quality (OFMQ) used chart abstraction to track EPSDT examination rates for SoonerCare Plus Medicaid managed care recipients from 1995 through 1998. During the abstractions, an examination was interpreted as an EPSDT screen if a comprehensive health and development history plus a comprehensive unclothed physical examination were recorded. Examination rates have improved from 1995 when there was a documented 17.6% completion rate. The 1998 documented rate of completion was 60.0%. Trend analysis shows significant improvement over the four-year period. The results also suggest the necessity for continued improvement in the provision of documented EPSDT examinations to individuals in Medicaid managed care plans in Oklahoma.

Predicting percentage of intramuscular fat using two types of real-time ultrasound equipment.

In the present study, 500 steers were used to develop models for predicting the percentage of intramuscular fat (PIMF) in live beef cattle. Before slaughter, steers were scanned across the 11th and 13th ribs using Aloka 500V (AL-500) and Classic Scanner 200 (CS-200) machines. Four to five images were collected per individual steer using each machine. After slaughter, a cross-sectional slice of the longissimus muscle from the 12th rib facing was used for chemical extraction to determine actual carcass percentage of intramuscular fat (CPIMF). Texture analysis software was used by two interpreters to select a region for determination of image parameters, which included Fourier, gradient, histogram, and co-occurrence parameters. Four prediction models were developed separately for each of AL-500 and CS-200 based on images captured by the respective machines. These included models developed without transformation of CPIMF (Model I), models based on logarithmic transformation of CPIMF (Model II), ridge regression procedure (Model III), and principal component regression procedure (Model IV). Model R2 and root mean square error of AL-500 Models I, II, III, and IV were 0.72, 0.84%; 0.72, 0.85%; 0.69, 0.91%; and 0.71, 0.86%; respectively. The corresponding R2 and root mean square error values of CS-200 Models I, II, III, and IV were 0.68, 0.87%; 0.70, 0.85%; 0.64, 0.94%; and 0.65, 0.91%; respectively. Initially, AL-500 and CS-200 prediction models were validated separately on an independent data set from 71 feedlot steers. The overall mean bias, standard error of prediction, and rank correlation coefficient across the four AL-500 models were 0.42%, 0.84%, and 0.88, respectively. For the four CS-200 models, the corresponding overall mean values were 0.67%, 0.81%, and 0.91, respectively. In a second validation test, only Model II of AL-500 and CS-200 was evaluated separately based on data from 24 feedlot steers. The overall mean bias, absolute difference, and standard error of prediction of AL-500 Model II were 0.71, 0.92, and 0.98%. For CS-200 Model II, the corresponding values were 0.59, 0.97, and 1.03%. Both AL-500 and CS-200 equipment can be used to accurately predict PIMF in live cattle. Further improvement in the accuracy of prediction equations could be achieved through increasing the development data set and the variation in PIMF of cattle used.

Signal-detection analysis of group decision making.

How effectively can groups of people make yes-or-no decisions? To answer this question, we used signal-detection theory to model the behavior of groups of human participants in a visual detection task. The detection model specifies how performance depends on the group's size, the competence of the members, the correlation among members' judgments, the constraints on member interaction, and the group's decision rule. The model also allows specification of performance efficiency, which is a measure of how closely a group's performance matches the statistically optimal group. The performance of our groups was consistent with the theoretical predictions, but efficiency decreased as group size increased. This result was attributable to a decrease in the effort that members gave to their individual tasks rather than to an inefficiency in combining the information in the members' judgments.

Consumer Assessment of Health Plans Survey (CAHPS) results for Oklahoma managed care Medicaid, 1997, 1998, and 1999.

Consumer satisfaction surveys have become an important source of information for purchasers and consumers of health care and health care organizations themselves. Individuals receiving health care provide valuable information regarding access, use of services, and satisfaction with care that can be used for multiple evaluative purposes. The Oklahoma Health Care Authority has adopted the Consumer Assessment of Health Plans Survey (CAHPS) to measure patient satisfaction for the SoonerCare managed care programs. The Oklahoma Foundation for Medical Quality administered the surveys. The adult and child CAHPS core questionnaires served as the basis for the general surveys in 1997 and 1998. The CAHPS for Children with Special Needs survey results and the Pediatric Adaptation of the CAHPS Behavioral Health Survey results were administered in 1999 for baseline measures. Results indicated an overall increase in consumer satisfaction levels across the two CAHPS core questionnaires. Baseline measures for special needs populations were also established.

Immunization rate comparison for Oklahoma Medicaid managed care population by age two: 1995-1998.

Processes of care are used as one measure for the quality of care rendered by providers. One example is the immunization of children by the age of two. The Oklahoma Health Care Authority, with the Oklahoma Foundation for Medical Quality, has been tracking childhood immunization rates from 1995 through 1998. The rate calculated included the medical record data and the Oklahoma Statewide Immunization Information System (OSIIS) data set. The standards were based on Advisory Committee on Immunization Practices recommendations and Quality Assurance Reform Initiative standards. The rate of provision of documented immunizations in the Medicaid managed care population under the age of two has improved markedly from 1995 to 1998. The trend analysis suggests there might be areas for continued improvement in the provision of immunization to individuals in Oklahoma's Medicaid managed care population. Further, the OSIIS data is critical for maintaining a uniform data set for immunization information.

The United States Army and malaria control in World War II.

The United States Army faced difficult malaria control problems both at home and abroad during World War II. This challenge forced the Army to develop new tools and strategies for use in malarious areas where fighting was occurring. Due to the severe malaria problems being faced in some combat areas and the need to solve these problems quickly, intensive malaria research and operational programs were developed and implemented. With these concerted efforts and the simultaneous development of new control technologies, malaria was successfully controlled in most locations. In order to accomplish this high level of control both in the US and overseas, the Army developed a very organized approach to the malaria problem and implemented it in an effective manner. The creation of new technical solutions was also strongly emphasized and out of this effort came the development of effective antimalaria drugs to replace quinine, of new insecticides and of more effective systems for delivering these insecticides. Some of the major new tools which came out of this research were DDT and drugs such as Atabrine and chloroquine. The availability of Atabrine and DDT revolutionized malaria control throughout the world. The knowledge and experience gained through the use of these new tools by the US Army and other agencies in World War II provided the basis for a new optimism regarding malaria control which then led to the development of the global malaria eradication strategy in the post-war years.

High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence.

PURPOSE: To evaluate the efficacy and feasibility of high-dose ifosfamide (HDI) at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte colony-stimulating factor (G-CSF) in adult patients with sarcomas. PATIENTS AND METHODS: Between July 1991 and February 1994, 74 patients with sarcomas (37 bone and 37 soft tissue) were treated on two simultaneous phase II studies that evaluated HDI given as a continuous infusion over 74 hours. G-CSF was started on day 5 at 5 microg/kg/d until recovery of granulocyte count. Additionally, between March 1993 and March 1994, 15 similar patients with previously treated bone or soft tissue sarcomas were treated on a pilot study in which the same total dose of ifosfamide was administered by a bolus schedule, along with mesna and G-CSF. Patients were treated until maximal response, and where possible, surgical resection of gross disease was performed. RESULTS: Seventy-two patients from the phase II study using continuous infusion are assessable for response. Four complete responses (CRs) and 17 partial responses (PRs) were noted, for an overall response rate of 29% (95% confidence interval [CI], 19% to 39%). The response rate was 40% (95% CI, 24% to 56%) for bone sarcomas and 19% (95% CI, 6% to 32%) for soft tissue sarcomas. Fourteen patients from the pilot study that used a bolus schedule are assessable for response. One CR and seven PRs were noted, for an overall response rate of 57% (95% CI, 31% to 83%) and a response rate of 45% for soft tissue sarcomas. Two patients developed grade 3 to 4 renal toxicity, three developed grade 3 CNS toxicity, one had possible grade 3 cardiac toxicity, and two developed severe painful peripheral neuropathy. There were no treatment-related deaths. CONCLUSION: HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas. There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion.

Convergent and discriminant validity of measures of parenting efficacy and control.

Examined the convergent and discriminant validity of the Parent Attribution Test (PAT; Bugental, Blue, & Cruzcosa, 1989), the Parental Locus of Control Scale (PLOC; Campis, Lyman, & Prentice-Dunn, 1986), and the Parenting Sense of Competence-Efficacy Scale (PSOC-Efficacy; Johnston & Mash, 1989) in 3 samples of community mothers. In the 1st 2 samples, mothers also completed measures of negative affect and social desirability. In the 3rd sample, the PAT and PSOC-Efficacy scales were administered with measures of adult attachment style and child behavior problems. There was weak support for the convergent validity of the measures. Moreover, the discriminant validity of the measures was not adequately demonstrated. Our results suggest that PLOC and PSOC-Efficacy scores may reflect distress and response style as well as beliefs about parenting. Scores on the PAT, although less influenced by response style and distress, appear to reflect a different dimension of efficacy than that assessed by other self-report measures.

Effect of dietary protein and estradiol-17 beta on growth and insulin-like growth factor I in cattle during realimentation.

Forty-eight medium-framed, crossbred steers (average BW = 268 +/- 20 kg) were limit-fed a 35% concentrate diet to gain approximately .10 kg/d during a 66-d restriction (REST) period. This was followed by a 98-d realimentation (REAL) period in which steers were allotted to a 3 x 2 factorial arrangement of treatments. Treatments were 80% concentrate diets containing 9, 12, or 15% CP, and implantation of one-half of the steers with 24 mg/steer of estradiol-17 beta (E2; Compudose). The allotted steers were distributed across four pens (12 steers/pen) with each pen containing two replicates of each treatment combination. Individual feed intakes were monitored using a Calan gate system. Each steer had ad libitum access to its respective diet. Longissimus muscle area and fat thickness at the 12th rib were measured using real-time ultrasound. Dry matter intake was not affected by CP or E2 through d 56. Steers fed 9% CP weighed less (quadratic, P < .05) after d 14 than steers fed 12 or 15% CP due to slower (quadratic, P < .05) gains during this initial period. Implantation increased (P < .05) ADG from d 15 to 56 resulting in heavier BW (P < .05) on d 56 and 98. Increasing concentrations of dietary CP resulted in linear (P < .05) increases in longissimus muscle area on d 28 and 56, and fat thickness on d 98. Serum IGF-I concentrations were lowest on d -21 of REST and highest on d 28 of REAL (quadratic, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma.

PURPOSE: To evaluate the clinical safety and ability of PIXY321, a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage myelosuppression. PATIENTS AND METHODS: PIXY321 was administered by subcutaneous injection twice daily (25 to 1,000 micrograms/m2/d) over 14 days to 24 chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four weeks later, a second cycle of CyADIC was administered, followed by 14 days of PIXY321. RESULTS: Treatment with PIXY321 was well tolerated. Local skin reactions and constitutional symptoms were the main side effects. The dose-limiting toxicity was not encountered; however, headache and fatigue were more frequent at the highest dose (1,000 micrograms/m2). PIXY321 before chemotherapy elicited a modest increase in the WBC count (consisting mainly of mature neutrophils), platelets, and corrected reticulocyte counts (all P < .001). Following chemotherapy, PIXY321 at effective doses (500 to 1,000 micrograms/m2/d), significantly reduced both the degree (mean nadir, 70 v 310/microL; P = .016) and duration (mean days < 500/microL, 6.6 v 3.9 days; P = .002) of neutropenia. Cumulative thrombocytopenia was not observed during the first two cycles of CyADIC (mean nadir platelet count, 103 v 95 x 10(3)/microL, in cycles no. 1 and 2, respectively; P = NS). Compared with our historic control data, the mean nadir platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for a dose response, since the mean percentage change in nadir platelet values from cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the peak effect observed at 750 micrograms/m2/d. CONCLUSION: These results suggest a potential clinical role for PIXY321 in attenuating the cumulative multilineage hematopoietic toxicity of chemotherapy.

Ornithodoros (Alectorobius) spheniscus n. sp. [Acarina: Ixodoidea: Argasidae: Ornithodoros (Alectorobius) capensis group], a tick parasite of the Humboldt penguin in Peru.

Ornithodoros (Alectorobius) spheniscus n. sp., described from wild-caught and laboratory-reared females, males, nymphs, and larvae parasitizing the Humboldt Penguin, Spheniscus humboldti Meyen, is the fifth species of the Ornithodoros (Alectorobius) capensis group to be recognized in the Neotropical Region. A related Peruvian species, Ornithodoros (Alectorobius) amblus Chamberlin, also parasitizes S. humboldti but is recorded from a wider range of marine birds breeding on the Pacific coast and offshore islands, where the birds congregate to feed on the rich fish fauna usually produced by the Humboldt current. Differential criteria are provided for the new species, O. (A.) amblus, and Ornithodoros (Alectorobius) yunkeri Keirans, Clifford, and Hoogstraal of the Galapagos. These 3 members of the O. (A.) capensis group parasitize marine birds associated with the Humboldt current in western South America and the Galapagos. Persons visiting Humboldt Penguin breeding sites in caves and on barren coastal ledges are eagerly attacked by nymphal and adult O. (A.) spheniscus and suffer afterward from pruritus and slowly-healing blisters. The O. (A.) spheniscus life cycle required 128 to 193 days in the laboratory and, as typical of bird-parasitizing members of the subgenus Alectorobius, the first nymphal instar did not feed.

The community as preclinical classroom: experience with a first-year clerkship.

The required first-year clerkship in family and community medicine at the University of Massachusetts Medical School is a major curricular innovation which has implications for physician education. Students have lived in communities and worked in health service settings with field sponsors, under full-time faculty guidance, in all regions of Massachusetts. This has been one answer to the school's mandate to address the physician maldistribution problem. The goals and objectives and the teaching methods used to implement the program are described. These lessons were drawn from the program experience: community medicine clerkships belong in the first year of the curriculum; full-time medical school faculty working with the field sponsor promotes an optimal learning environment; long-term evaluation remains an important consideration. The first eight years of experience with the clerkship have demonstrated its value, and it should be considered for inclusion in the curriculum of other medical schools.