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Lay Abstract: Autistic people are more likely to consider suicide than non-autistic people, with transition-aged youth (ages 16-21 years) at potentially the highest risk. Research has also shown that difficulties with executive functioning (e.g., difficulties with organization, sequencing, and decision-making) may heighten suicide risk among non-autistic people, but it is not clear whether this is also true for autistic people. This study explored this question by asking 183 transition-aged autistic youth about their experience with suicidal behavior and examining the relationship between their responses and additional measures of depression, autistic traits, and executive function skills. About one-third of autistic transition-aged youth (33.3%) said that they had experienced thoughts of hurting themselves with the intent to end their lives (i.e., suicidal ideation). Both depression and executive function challenges predicted suicide risk (i.e., participants who experienced depression were more likely to have had suicidal thoughts than those who had not, and participants who had more difficulty with executive function skills were more likely to have had suicidal thoughts than those who had less difficulty). These findings suggest that executive functioning, a common area of difficulty among autistic people, is an important indicator of suicide risk in this population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lay Abstract: Although many autistic individuals have additional mental health conditions, most have a hard time getting services from mental health providers. One reason why these services can be hard to access is that many mental health providers do not feel confident in their ability to provide services to autistic individuals. To share autism expertise with local community providers and boost their confidence in working with autistic individuals, we created a mental health version of the Extension for Community Healthcare Outcomes (Project ECHO) Autism virtual teleconsultation program. In this pilot study, we recruited 51 community mental health providers to participate in Project ECHO Autism. During each biweekly session, providers received information from autism experts about how to tailor mental health interventions (e.g. attention-deficit hyperactivity disorder or anxiety interventions) for use with autistic individuals. They also had the opportunity to ask questions and get advice on their current cases. At the end of the 6-month study, mental health providers showed improvements in their confidence, in their knowledge of autism, and in their problem-solving skills. Nearly half (45%) of these providers participated from rural counties, suggesting that the Project ECHO Autism teleconsultation model was able to reach mental health providers who might not have been able to get training otherwise. This study supports the feasibility of using Project ECHO Autism to share autism knowledge with mental health providers, consequently expanding mental health service options for autistic individuals with co-occurring mental health conditions.

Objective: The heterogeneous symptom presentation of autism spectrum disorder (ASD) requires clinicians to consider each child's unique constellation of symptoms and tailor intervention accordingly. Treatment moderators, though necessary to guide evidence-based treatment decisions, are significantly under-studied. This brief report aims to expand on previous literature by providing an overview of characteristics which may influence treatment outcome and specifying future directions to build on this preliminary evidence base., Method: A subset of treatment modalities was identified from the National Clearinghouse on Autism Evidence and Practice Review Team's most recent report including discrete trial early intensive behaviorally based treatment, social skills training, and cognitive behavioral interventions. Within these treatment modalities, individual interventions with significant support were specifically discussed. Due to the lack of research on treatment moderators, a discussion of significant predictors of treatment outcome is also included., Results: Preliminary evidence suggests that overall, treatment intensity, duration, and parent involvement are the most consistently identified predictors (and in some studies, moderators) of treatment outcome; sessions which occur more frequently, continue for longer periods of time, and include parent training or coaching may yield the best outcomes. Other characteristics, including age and IQ, have been widely debated, with differing results found across treatment modalities., Conclusions: The sparsity of research demonstrates a clear need for continued research on moderators to guide clinical judgment. Future studies that recruit larger samples targeting specific ASD symptoms at specific ages may be more adequately powered to detect these moderating effects.

Although widely conceived as distinct conditions, higher-functioning autism spectrum disorder (ASD) and schizoid personality disorder (schizoid PD) share similar clinical symptomatology. This study explored the relationship between the two disorders by collecting extensively validated measures of autistic trait burden (Social Responsive Scale, Second Edition) and schizoid PD affectation (Diagnostic Interview for Genetic Studies) from clinically ascertained verbal males with and without autism ages 12 to 25 years (N = 72) via parent, teacher, and self-report. Although only a small minority of adolescents with ASD met full diagnostic criteria for schizoid PD, participants with ASD endorsed a continuous distribution of schizoid PD traits that reflected a pronounced pathological shift in comparison with those in the control group, with one half of ASD males experiencing three or more Diagnostic and Statistical Manual of Mental Disorders, 4th Edition schizoid PD criterion items "often" or "almost always." Results suggest significant amplification of schizoid PD trait burden in adolescents with ASD. ASD-specific interventions should be considered for patients with schizoid PD with premorbid histories of ASD.

Background and Purpose: In 2015, an invitational think tank was convened by the Fellows of the American Association of Nurse Practitioners to update the 2010 Nurse Practitioner (NP) Research Agenda Roundtable. This effort was undertaken to provide guidance for future health care research. The purpose of this article is to introduce the process used for conducting four reviews that address critical topics related to specific research priorities emanating from the 2015 NP Research Agenda Roundtable. The four reviews are published in this issue of Journal of the American Association of Nurse Practitioners (JAANP) to address the state of current research relevant to NP policy, workforce, education, and practice., Methods: This introductory article provides an overview of the systematic process used to evaluate the four topical area. The type of review selected, the search strategy, critical appraisal, data extraction, and data synthesis will be further described in the four review articles., Conclusions: Four reviews that examine literature regarding specific aims important to NPs will address strengths as well as gaps in the literature., Implications for Practice: The knowledge offered by the four reviews has the potential to inform future research, which will benefit NPs and other health care stakeholders.

Background and Purpose: Data from national surveys on the practice of nurse practitioners (NPs) provides valuable information on aspects of practice, demographic characteristics of providers and patients, plans for continued employment, and role satisfaction. The American Association of Nurse Practitioners (AANP) has been conducting the AANP Sample Survey since 1988., Methods: The most recent AANP Sample Survey was conducted in 2016 with a random stratified survey of 40,000 NPs. Data were collected bimodally, by internet and mail surveys. Responses were received from 3,970 respondents (9.9% response rate), with 335 respondents reporting NP certification in acute care as adult-gerontology acute care and/or pediatric acute care., Results: Almost all acute care nurse practitioners (ACNPs) reported that they were clinically practicing in 2016 (99.3%), with the top three areas encompassing cardiovascular (20.5%), critical care (12.1%), and hospitalist roles (6.3%). More than 1 in 4 ACNPs worked in a hospital inpatient setting, with 16.1% reporting work in a hospital outpatient clinic, 7.7% in a private group practice, 6.5% at a public university, and some in combined roles covering both inpatient and outpatient care, or on consultation service or specialty-based teams. On average, 34.1% of the patients ACNPs saw were between the ages of 66 and 85 years, and 11.2% were 85 years and older. The top 3 medication classes in which ACNPs regularly prescribe were diuretics (31.9%), analgesic narcotics (31.2%), and antibiotics (27.3%). Majority (88%) report satisfaction with the role, and approximately one third (31.1%) expect to continue to work in their current practice for more than 10 years., Implications for Practice: The findings of the 2016 AANP National NP Sample Survey data related to ACNP practice identify expansion of work settings, practice consistent with acute care scope of practice, role satisfaction, and intent to continue working. Continued monitoring of practice components and employment is indicated to track ACNP workforce trends.

Background and Purpose: While there is a preponderance of studies that demonstrate the quality of nurse practitioner (NP) practice, little is known on the practice style of NPs. The Direct Observation of Nurse Practitioner Care study provided the first national direct observation and characterization of patient care delivered by primary care NPs., Methods: The setting for this study was ambulatory care practices of NPs located throughout the United States. A nested sample was utilized, consisting of 22 NPs during visits with 245 patients. Observational data were collected during each visit using the Davis observation code (DOC). Patient information was collected from chart reviews and postvisit surveys. Each NP filled out a demographic and practice survey., Conclusions: Visits to NPs were 18 min on average, and were most frequently for new/acute problems (45.1%) or routine chronic problems (30.2%). Overall, NPs spent the most time planning treatment, history taking, and providing health education. Topics that NPs frequently provided health education about included medication action and side effects, disease process education, diet, and nutrition., Implications for Practice: Data from this study will allow for detailed characterizations of a patient-NP visit and average length of the visit and the time use based on the DOC., (©2016 American Association of Nurse Practitioners.)

Background and Purpose: The purpose of this study was twofold: to describe the average cost of nurse practitioner (NP) tuition based on degree program, program type, and geography; and to compare the cost of NP tuition to medical school tuition., Methods: A listing of all NP degree granting universities was obtained from the American Association of Colleges of Nursing during the fall of 2014, and tuition data were obtained from university websites. Medical school tuition data were obtained online during the fall of 2014 from the American Association of Medical Colleges. Average 1-year tuition rates were calculated for NP programs and medical schools and compared across private and public institutions., Conclusions: Average 1-year resident tuition for public university NP programs ranges between $8671 and $11,077 based on type of program. The cost of 1-year NP program tuition at the master's and the doctoral level is much lower than the cost of 1-year medical school tuition at both private and public universities., Implications for Practice: NPs can perform many of the same services as physicians in the primary care setting with comparable outcomes, yet the cost of educating NPs is much lower. NPs are a cost-effective solution to the healthcare workforce shortage., (©2015 American Association of Nurse Practitioners.)

Background: Nurse practitioners (NP) and physician assistants (PA) serve as independent or semiautonomous providers and as fundamental members of healthcare teams., Purpose: Differentiating roles of health professionals is needed for optimal employment utilization. Clinically practicing PAs and NPs were characterized., Methodology: Data included wage and workforce projections to 2022.Variables included number practicing, age, gender, race, ethnicity, education, principal employer, practice specialty, and wages., Results: Health delivery establishments employed 88,110 PA and 113,370 NP clinicians in 2013. Both were predominantly female: NPs were older (49 years) on average than PAs (38 years). A significant number of them practiced in physicians' offices or in acute care hospitals. Median wages were at parity. Growth predictions from 2012 to 2022 were 31%-35%., Conclusions: PAs and NPs constitute 20% of the composite clinician labor force (MD, DO, PA, NP). Labor market analysis suggests they are in demand. A majority of NPs and a third of PAs work in primary care fields. Their collective projected growth suggests a solution to emerging workforce shortages and an ability to help meet healthcare demands., Implications for Practice: Adaptability to changing roles, especially in primary care and underserved areas, makes them facile responders to market demands in a continuously evolving healthcare environment., (©2015 American Association of Nurse Practitioners.)

I analyze the case of humanitarian pro-migrant activists in southern Arizona between 2000 and 2010 to explore how contending groups wield law and legality claims in a dynamic policy environment. Humanitarian activists both evade and engage the law. They appeal to a higher law to elude charges that they are acting illegally, while seeking assurances that their actions are within the law. Law enforcement agents rely on the authority and technical neutrality of the law in redefining humanitarian aid as illegal, while expanding their own claims to carry out humanitarian work. This case study of advocacy on behalf of “illegal” migrants highlights how both activists and those who enforce the law redefine legality in strategic ways.

Asthma poses a significant burden on patients, families, health care providers, and the medical system. While efforts to standardize care through guidelines have expanded, difficulty in managing severe asthma has encouraged research about its pathobiology and treatment options. Novel biologic therapeutics are being developed for the treatment of asthma and are of potential use for severe refractory asthma, especially where the increased cost of such agents is more likely justified. This review will summarize currently approved (omalizumab) and investigational biological agents for asthma, such as antibodies, soluble receptors, and other protein-based antagonists, and highlight recent published data on efficacy and safety of these therapies in humans. As these newer agents with highly targeted pharmacology are tested in asthma, we are also poised to learn more about the role of cytokines and other molecules in the pathophysiology of asthma.

Introduction: We assessed the prevalence of 7 childhood adversities (psychological, physical, and sexual abuse; household mental illness; household substance abuse; maternal battery; and incarceration of a household member) and the associations of those adversities with health outcomes., Methods: Using data from 5,378 people who responded to the 2002 Texas Behavioral Risk Factor Surveillance System survey (which included questions about childhood adversity), we created 4 groups: no childhood abuse or household dysfunction, childhood abuse only, household dysfunction only, and both childhood abuse and household dysfunction. We examined groups by sociodemographic variables and the association with current smoking, obesity, and self-rated health., Results: Among adult respondents, 46% reported at least 1 childhood adversity. Reports of both household dysfunction and abuse were significantly lower for college graduates than for people with less education. For those with both abuse and household dysfunction, the odds of current smoking were 1.9 and for obesity were 1.3. Compared to people without childhood adversities, people who experienced childhood adversities more frequently reported having fair or poor general health status., Conclusion: Childhood adversities are common among Texas adults. People with childhood adversities are more likely to be socioeconomically disadvantaged, less educated, and have difficulties maintaining employment in adulthood compared to people with no adversities. Moreover, childhood adversities appear to be associated with health problems such as current smoking, obesity, and poor or fair general health among Texas adults.

We conducted population-based surveys on direct-to-consumer nutrigenomic testing in Michigan, Oregon, and Utah as part of the 2006 Behavioral Risk Factor Surveillance System. Awareness of the tests was highest in Oregon (24.4%) and lowest in Michigan (7.6%). Predictors of awareness were more education, higher income, and increasing age, except among those 65 years or older. Less than 1% had used a health-related direct-to-consumer genetic test. Public health systems should increase consumer and provider education and continue surveillance on direct-to-consumer genetic tests.

Agricultural workers are at risk for developing skin cancer due to exposures to ultraviolet radiation. Occupational health nurses implemented a skin cancer screening during an agricultural trade show to facilitate primary and secondary prevention of skin cancer through risk assessment, visual skin examination, counseling, and education. The purpose of this article is to present an evidence-based practice model that describes the demographics of a skin cancer screening population, self-reported risk factors, the occurrence of presumptive diagnoses, and compliance with health-related recommendations. Eighty-eight individuals were screened. Thirty-nine (44%) of all screened participants were referred for further evaluation. Of the 39 referrals, 16 (41%) were recommended for biopsy. One month after the screening, 21 (54%) of the participants had completed or arranged follow-up. Status of the identified lesion was also explored. General comments yielded statements that demonstrated appreciation for the screening, teaching, reminders, and encouragement.

Several mass strandings of beaked whales have recently been correlated with military exercises involving mid-frequency sonar highlighting unknowns regarding hearing sensitivity in these species. We report the hearing abilities of a stranded juvenile beaked whale (Mesoplodon europaeus) measured with auditory evoked potentials. The beaked whale's modulation rate transfer function (MRTF) measured with a 40-kHz carrier showed responses up to an 1,800 Hz amplitude modulation (AM) rate. The MRTF was strongest at the 1,000 and 1,200 Hz AM rates. The envelope following response (EFR) input-output functions were non-linear. The beaked whale was most sensitive to high frequency signals between 40 and 80 kHz, but produced smaller evoked potentials to 5 kHz, the lowest frequency tested. The beaked whale hearing range and sensitivity are similar to other odontocetes that have been measured.

Auditory evoked potential (AEP) measurements of two Florida manatees (Trichechus manatus latirostris) were measured in response to amplitude modulated tones. The AEP measurements showed weak responses to test stimuli from 4 kHz to 40 kHz. The manatee modulation rate transfer function (MRTF) is maximally sensitive to 150 and 600 Hz amplitude modulation (AM) rates. The 600 Hz AM rate is midway between the AM sensitivities of terrestrial mammals (chinchillas, gerbils, and humans) (80-150 Hz) and dolphins (1,000-1,200 Hz). Audiograms estimated from the input-output functions of the EPs greatly underestimate behavioral hearing thresholds measured in two other manatees. This underestimation is probably due to the electrodes being located several centimeters from the brain.

Salmonella enterica subsp. enterica serovar Typhimurium var. Copenhagen isolates from a heifer-raising operation and from 11 dairy herds that had their calves contracted to the heifer-raising operation were examined for their phenotypic and genotypic characteristics. Results of the study showed that the heifer-raising operation could serve as a clearinghouse for Salmonella serovar Typhimurium var. Copenhagen and perhaps other Salmonella serotypes.

Introduction: Family history of diabetes has been recognized as an important risk factor of the disease. Family medical history represents valuable genomic information because it characterizes the combined interactions between environmental, behavioral, and genetic factors. This study examined the strength and effect of having a family history of diabetes on the prevalence of self-reported, previously diagnosed diabetes among adult participants of the National Health and Nutrition Examination Survey 199-2002., Methods: The study population included data from 10,283 participants aged 20 years and older. Gender, age, race/ethnicity, poverty income ratio, education level, body mass index, and family history of diabetes were examined in relation to diabetes status. Diabetes prevalence estimates and odds ratios of diabetes were calculated based on family history and other factors., Results: The prevalence of diabetes among individuals who have a first-degree relative with diabetes (14.3%) was significantly higher than that of individuals without a family history (3.2%), corresponding to a crude odds ratio of five. Both prevalence and odds ratio estimates significantly increased with the number of relatives affected with diabetes. Family history was also associated with several demographic and risk factors., Conclusion: Family history of diabetes was shown to be a significant predictor of diabetes prevalence in the adult U.S. population. We advocate the inclusion of family history assessment in public health prevention and screening programs as an inexpensive and valuable source of genomic information and measure of diabetes risk.

Data from behavioural observations and acoustic recordings of free-ranging bottlenose dolphins (Tursiops truncatus) were analysed to determine whether signature whistles are produced by wild undisturbed dolphins, and how whistle production varies with activity and group size. The study animals were part of a resident community of bottlenose dolphins near Sarasota, Florida, USA. This community of dolphins provides a unique opportunity for the study of signature-whistle production, since most animals have been recorded during capture-release events since 1975. Three mother-calf pairs and their associates were recorded for a total of 141.25 h between May and August of 1994 and 1995. Whistles of undisturbed dolphins were compared with those recorded from the same individuals during capture-release events. Whistles were conservatively classified into one of four categories: signature, probable signature, upsweep or other. For statistical analyses, signature and probable signature whistles were combined into a 'signature' category; upsweep and other whistles were combined into a 'non-signature' category. Both 'signature' and 'non-signature' whistle frequencies significantly increased as group size increased. There were significant differences in whistle frequencies across activity types: both 'signature' and 'non-signature' whistles were most likely to occur during socializing and least likely to occur during travelling. There were no significant interactions between group size and activity type. Signature and probable signature whistles made up ca. 52% of all whistles produced by these free-ranging bottlenose dolphins.

While searching for an object in a cluttered scene, in some situations, the visual system adopts a pre-attentive parallel search, where the time taken is independent of the number of items in the scene. In others, the search is serial, time taken being a function of the set size. We show that detecting the number of targets (2, 3 or 4) that differ in depth from background items is a parallel process, but only when they are all in the same surface in depth. The search is serial if the targets are in different depth planes, but parallel even if the targets were on a surface tilted in depth, showing that surface segregation influences a parallel, apparently pre-attentive, stage.

A collaborative effort between community health faculty in an upper division nursing program and nurses from a nearby agricultural health and research center resulted in an educational program focused on occupational health and safety issues in the agricultural industry. The 3 hour class was presented each semester between 1997 and 1999 to RN students enrolled in a community health organization class. In addition to information about the health and safety hazards in agriculture, the nursing students learned about the center's research projects and clinical services available to the farming community. A follow up survey was mailed to the nursing students to evaluate the effectiveness and relevance of the occupational health program by identifying the proportion of the nurses' caseloads spent on occupational health problems, and whether the information and materials presented in the class were relevant to practice. Results showed that even though the surveyed nurses were employed in nonoccupational practice settings, nearly everyone rated the occupational health information as useful. Findings also revealed that although nurses in nonoccupational practice can spend nearly a quarter of their time caring for clients with work related health problems, they may lack adequate educational preparation to do so.

Perspective is usually considered a monocular pictorial cue, distinct from other cues such as occlusion and stereopsis. We cut across these distinctions by asking whether purely binocular (cyclopean) contours, created by stereoscopically shifting a region of homogeneous texture nearer or further than its surround, can act as a linear-perspective cue and whether the contours' ability to do this is influenced by their surface belongingness. We found that the left/right orientation of cyclopean trapezoids nearer than a surround strongly influenced perceived slant, showing that perspective constraints are applied to stereoscopically derived contours. Further regions, however; appeared as surfaces seen through a trapezoidal aperture. Because the aperture "owned" the trapezoidal contours, their orientation had little effect on perceived slant. We conclude that the application of perspective constraints depends critically on how contours are classified by stereo-specified occlusion relationships among surfaces and that perspective, stereopsis, and occlusion are not distinct processing systems.

It is clear that research is an increasing role of managers and is crucial to the financial and clinical success of a home health agency. This article has described the important considerations and approaches managers must consider to integrate research effectively. By following one agency's involvement with a researcher on a project, strategies emerge that managers can use to integrate research with staff in everyday practice.

Family caregivers recognize the need for responsible, dependable home care services. When the services of the home care agency are required, it is often the aide who delivers the day-to-day care, whereas the home care nurse is responsible for providing coordination and supervision. The findings of this study provide the nurse with a better understanding of the relationship between home care aides and family caregivers.

Cytomegalovirus induces serious disease in immunosuppressed individuals, often from an "activated" persistent infection. Whether the infection is chronically active or latent is unknown. Using murine cytomegalovirus (MCMV) in mice as a model system, we examined persistent infections in spleen, lung, and bone marrow of infected animals. At 28 days after infection, no virus could be recovered from any organs tested except salivary glands, and here, virus was cleared by 48 days. Virus could be retrieved at all times by cocultivation of spleen or lung with permissive cells. In addition, MCMV DNA was always present in spleen, lung, and bone marrow. After acute infection, RNA from the MCMV immediate early-1 (ie-1) gene was routinely found only in the lung. In spleen and bone marrow, only one sample from each organ examined at these times contained ie-1 RNA, and the RNA in these two samples was present at levels comparable to that found in acute infection. This suggests that the virus had reactivated. The ie-1 RNA found in the lung was present at a much lower RNA:DNA ratio than that found at early times. Taken together, these results indicate that persistent MCMV exists simultaneously in both chronic active and latent states.

Numbers of protozoa in the subsurface of aviation gasoline and jet fuel spill areas at a Coast Guard base at Traverse City, Mich., were determined. Boreholes were drilled in an uncontaminated location, in contaminated but untreated parts of the fuel plumes, and in the aviation gasoline source area undergoing H(2)O(2) biotreatment. Samples were taken from the unsaturated zone to depths slightly below the floating free product in the saturated zone. Protozoa were found to occur in elevated numbers in the unsaturated zone, where fuel vapors mixed with atmospheric oxygen, and below the layer of floating fuel, where uncontaminated groundwater came into contact with fuel. The same trends were noted in the biotreatment area, except that numbers of protozoa were higher. Numbers of protozoa in some contaminated areas equalled or exceeded those found in surface soil. The abundance of protozoa in the biotreatment area was high enough that it would be expected to significantly reduce the bacterial community that was degrading the fuel. Little reduction in hydraulic conductivity was observed, and no bacterial fouling of the aquifer was observed during biotreatment.

Recently it has been claimed by Livingstone and Hubel that, of three anatomically and functionally distinct visual channels (the magnocellular, parvocellular interblob, and blob channels), only the magnocellular channel is involved in the processing of stereoscopic depth. Since the magnocellular system shows little overt colour opponency, the reported loss of the ability to resolve random-dot stereograms defined only by colour contrast seems consistent with this view. However, Julesz observed that reversed-contrast stereograms could be fused if correlated colour information was added. In the present study, 'noise' (non-corresponding) pixels were injected into random-dot stereograms in order to increase fusion time. All six subjects tested were able to achieve stereopsis in less than three minutes when there was only correspondence in colour and not in luminance, and three when luminance contrast was completely reversed. This ability depends on information about the direction of colour contrast, not just the presence of chromatic borders. When luminance and chromatic contrast are defined in terms of signal-to-noise ratios at the photoreceptor mosaic, chromatic information plays at least as important a role in stereopsis as does luminance information, suggesting that the magnocellular channel is not uniquely involved.

Although herpes simplex virus type 1 (HSV-1) is known to reside latently in trigeminal ganglia between episodes of reactivation, the mechanisms involved in restricting the virus to this state are not understood. Using in situ nucleic acid hybridization methods, we show that there is HSV-encoded RNA in ganglion cells from 10 of 12 seropositive and zero of three seronegative patients studied at autopsy. Transcripts mapping to the region encoding the immediate-early polypeptide ICPO and the latency-associated transcript (LAT) were detected in the nuclei of these neurons. No other region of the HSV-1 genome was found to be expressed. When carefully defined probes were used to identify the transcripts, RNA corresponding to the LAT and, rarely, to ICPO was found. These results suggest that HSV-1 latency is an active process and that the LAT may be involved in regulating viral genetic expression.

As contact lens practitioners, optometrists work in a nonsterile environment and on a nonsterile part of the human body. Our report describes 10 cases of eye infection related to contact lens wear. Practitioners need to be aware of the problems which can occur when a thoroughly sterilized contact lens is placed on an unsterile and biologically complex eye. We recommend taking swabs of the conjuctiva in all eyes where ocular inflammation is present. In those areas in which the professions of optometry and medicine meet, cooperation should exist. Improving our knowledge and skills in microbiology helps to facilitate such cooperation. Our experience has been most rewarding and interaction in this field with medical practitioners has been positive. The use of a high quality slitlamp is essential.

Following peripheral inoculation of experimental animals, herpes simplex virus type 2 (HSV-2) strains are more virulent than HSV-1 strains, and clinical studies suggest that they possess enhanced virulence in humans. One dramatic type-specific difference in virulence is observed following inoculation of the chorioallantoic membrane (CAM) of the chicken embryo: HSV-2, but not HSV-1, makes large pocks on the CAM, invades the mesoderm, generalizes in the embryo, and kills the chicken. These properties have been believed to be specific for HSV-2, and their molecular basis is unknown. We now report that an HSV-1 strain, ANG, behaves even more efficiently than HSV-2. In addition, we have transferred restriction fragments of ANG DNA to another HSV-1 strain, 17 syn+, conferring the CAM virulence phenotype on the normally CAM-avirulent 17 syn+. Like ANG, these recombinant viruses are 10(6)-fold more virulent (PFU/50%) lethal dose [LD50] ratio, less than or equal to 10(2)) than the parental 17 syn+ strain (PFU/LD50 ratio, greater than or equal to 10(8)). A molecularly cloned library of ANG DNA was used to identify two distinct regions containing the virulence functions. Transfer of sequences contained in either cloned ANG EcoRI fragment A (0.49 to 0.64 map units) or F (0.32 to 0.42 map units) DNA to 17 syn+ confers CAM virulence, whereas other cloned regions of the ANG genome do not. Using cloned DNA, we derived and plaque purified several virulent recombinant viruses with inserts from either the ANG EcoRI fragment A (INV-I) or F (INV-II) areas. In each instance, the transfer of the cloned INV-I or INV-II sequences enhanced virulence for the chicken embryo 10(6)-fold (PFU/LD50 ratio, less than or equal to 10(2]. In addition, the transfer of the cloned ANG EcoRI-F INV-II sequences resulted in a 10(3)-fold enhancement of neuroinvasiveness and virulence for mice. Following footpad inoculation, these recombinants kill mice with a PFU/LD50 ratio of approximately 10(3) (similar to HSV-2 strains) compared with 10(6) for 17 syn+. Thus, we have identified, cloned, and transferred two DNA regions from HSV-1 ANG which contain virulence genes (INV-I and INV-II) important in mesodermal invasiveness on the CAM and, in the case of INV-II, neuroinvasiveness in the mouse. In each instance, the recombinant HSV-1 viruses have attained enhanced virulence beyond that described for HSV-1 strains and similar to that seen with HSV-2.(ABSTRACT TRUNCATED AT 400 WORDS)

Thirteen temperature-sensitive (ts) mutants of HSV-1 were analysed for their capacity to establish latent infections in the brains of mice. Eleven of the mutants could be classified as latency-positive or -negative; two could not be assigned to either group. Leakiness of mutants in the brain and differences in particle/infectivity ratios were found not to play a role in the results. Ts+ revertants of selected latency-negative mutants regained the capacity to establish latent infections, indicating that it was the ts lesion in these agents which was involved in latency. Ultrastructural studies of neuroblastoma cells infected with various mutants and maintained at the restrictive temperature showed that no absolute correlations could be made between capacity to establish latent infection and synthesis of various morphologically identifiable virus products. Finally, from a comparison of latency characteristics with previously established polypeptide phenotypes of mutants it was concluded that one immediate early and one or more later virus functions are necessary for establishment and/or maintenance of the latent state.

In initial attempts to define the molecular events responsible for the latent state of herpes simplex virus, in situ hybridization was utilized to search for virally encoded RNA transcripts in latently infected sensory neurons. The use of cloned probes representing the entire viral genome indicated that transcripts encoded within terminal repeats were present. When the alpha genes encoding ICP-0, ICP-4, and ICP-27 and the gamma 1 gene encoding VP-5 were employed, only RNA transcripts hybridizing to the ICP-0 probe were detected. In latently infected cells, the ICP-0--related transcripts were localized principally in the nucleus; this was not the case in acutely (productively) infected neurons or in neurons probed for RNA transcripts coding for actin. In Northern blotting experiments, an RNA of 2.6 kilobases was detected with the ICP-0 probe. When single-stranded DNAs from the ICP-0 region were used as probes, RNA from the strand complementary to that encoding ICP-0 messenger RNA (mRNA) was the major species detected. This RNA species may play a significant role in maintaining the latent infection.

Sixteen weeks after inoculation, murine cytomegalovirus (MCMV) can no longer be detected in the tissues of mice. However, a 2-week course of immunosuppression with antilymphocyte serum and cortisone acetate results in reactivation and dissemination of the latent virus in all animals. In this study of reactivation, MCMV was first detected in the liver, usually during the first week of immunosuppression, and virus replication was shown to be restricted to hepatocytes. Subsequently, a viremia occurred, with spread of infection to other organs. The highest titers of virus were reached in salivary glands in which replication occurred in serous acinar cells. In the lung, virus-specific abnormalities were difficult to detect because of superimposed bacterial and fungal infections. However, interstitial pneumonitis could be produced when cortisone acetate was deleted from the immunosuppressive regimen. Although the site of virus latency has not been defined, this model system will be useful for study of reactivation of latent cytomegalovirus infection.

When the replicative defect in the HSV-1 temperature sensitive mutant tsI was repaired, the agent derived (RI-1) was found to possess an additional temperature sensitive lesion limiting its reactivation from the latent state. Thus, when spinal ganglia from latently infected mice were scored for reactivation by cocultivating them with indicator cells in vitro, significantly more were found to be positive at 31 degrees than at 38.5 degrees. To assess a possible relationship between reactivation and replication in neurons, the replication of RI-1 in murine C1300 neuroblastoma cells was studied. In these cells, RI-1 was severely restricted, and viral replication was delayed at 38.5 degrees. Serial passage of RI-1 in neuroblastoma cells at the restrictive temperature resulted in selection of an agent which gained both the capacity to replicate efficiently in neuroblastoma cells and reactivate from the latent state at 38.5 degrees. However, the replication pattern of this neuron adapted virus in mouse embryo fibroblasts remained unchanged from the parental RI-1. Taken together, these results indicate that RI-1 possesses a neuron specific temperature sensitive replicative lesion which is also manifest during reactivation from the latent state.

In the chicken, Marek's disease virus (MDV) induces a demyelinating peripheral neuropathy that, early in the course of the disease, is histopathologically indistinguishable from that seen in the Landry--Guillain--Barré syndrome in man. A continuing role for a productive infection in the pathogenesis of this disease is unlikely, since neither MDV nor MDV antigens can be characteristically detected in nerves or spinal ganglia examined at necropsy. The authors investigated the possible role of a latent viral infection by explanting and maintaining in vitro the sciatic nerves and spinal ganglia from diseased birds. In these tissues, viral specific products were induced and detected by immunofluorescence and ultrastructural methods early after explanation in well-isolated Schwann cells, satellite cells, and lymphocytes. Later, virus was detected in fibroblasts, macrophages, and neoplastic lymphoblastoid cells. Neurons and myelinating Schwann cells, in contrast, did not replicate the agent. Specific cell-mediated and humoral immune responses to chicken peripheral nerve and peripheral nerve myelin were demonstrated early in the course of the disease. When considered relative to potential pathogenetic mechanisms, these results suggest that Marek's disease neuropathy is initiated by the establishment of a latent viral infection in neuronal supporting cells. A specific immune response to viral-induced antigens on these cells could, in turn, result in subsequent demyelination.

The early lesions of Marek's disease in chickens are indistinguishable from those of the Landry-Guillain-Barré syndrome in human beings. Because of these similarities, and since the etiological agent (a herpesvirus) is known, Marek's disease can be meaningfully exploited as a model of the Landry-Guillain-Barré syndrome. Recent work in our laboratories has shown that the agent establishes latent infections in neuronal supporting cells and that affected birds mount cellular and humoral immunological reactions to peripheral nerve and myelin. Based on these findings, a working hypothesis for the pathogenesis of the disease is presented.

The effects of different drugs on memory function in epileptic patients were examined. Patients had clinically normal cognitive function, above average IQs and infrequent seizures. Compared with pre-treatment evaluation, treatment with phenytoin, but not with carbamazepine or sodium valproate, resulted in impaired memory performance after three months of treatment. Switching patients previously treated with phenytoin to carbamazepine resulted in an improvement in memory performance compared with that of patients remaining on phenytoin. Switching patients from carbamazepine to sodium valproate did not result in any change in performance compared with that of those remaining on carbamazepine. The results of these experiments suggest that phenytoin, but not carbamazepine or sodium valproate, causes impaired memory performance. The nature of the memory dysfunction and its clinical implications are discussed.

The rate and course of axoplasmic transport from the eighth dorsal root ganglion cell bodies into the sciatic nerve of the toad Bufo marinus were studied. Concentrated tritiated proline was hydraulically injected into a surgically exposed dorsal root ganglion of animals maintained at 19 +/- 0.5 degrees C. At postinjection intervals of 1, 6, and 10 h, the animals were sacrificed and the dorsal root, ganglion, and sciatic nerve were removed bilaterally. The dorsal roots and peripheral nerves were cut into 3 mm segments measured from the ganglion. In some experiments all tissues were prepared for liquid scintillation counting techniques. In others the ganglion and every fifth 3 mm nerve segment were fixed in Bouin's fixative for radioautography, and the remaining tissue segments were prepared for liquid scintillation counting methods. Scintillation counts (counts/min) of consecutive segments along the labeled nerve were plotted against distance (mm) for each animal. Examination of these profiles showed a peak of radioactivity in the injected ganglion for each animal that was followed distally by an abrupt drop in the adjacent segments of the nerve. Radioactivity remained relatively stable in subsequent segments forming a plateau and then dropped to baseline levels forming a wavefront in the distal portion of the peripheral nerves of the 6 and 10 h toads. Movement of this wavefront during the 6 to 10 h time interval provided evidence for an axoplasmic flow rate of about 120 mm/day. Radioautographs of the ganglion and representative segments along the sciatic nerve were examined with both bright- and dark-field microscopy. Accumulations of silver grains were observed overlying the injected ganglion cell bodies and labeled axons of the nerve. Values for the number of silver grains/unit area were obtained from dark-field radioautographs of the nerve segments through the use of a computer-microscope system. The relative amount of radioactivity present in the axons was thereby demonstrated. Radioautographic data confirmed the axoplasmic flow rate of about 120 mm/day determined by liquid scintillation counting methods for the bulk of radioactive materials transported at this fast rate. In addition, the evaluation of radioautographic data suggests that an even faster flow rate of 185-215 mm/day may exist for a small portion of the labeled materials transported in the axon.

It has been documented that KOS, a laboratory strain of herpes simplex virus type 1, is several orders of magnitude less neurovirulent than most other wild-type strains. Studies initiated to determine the functional nature of the block to neuroinvasiveness and to establish the genes involved have determined that, after footpad inoculation of mice, strain 17 syn+ induced neuropathologic signs (paralysis) at titers of 10(2) and yielded a PFU/50% lethal dose ratio of 10(4). In contrast, KOS was not lethal and did not induce paralysis at inoculation doses of 10(8) PFU. This reduced neurovirulence of KOS could not be explained by the lack of thymidine kinase activity, its inability to replicate in mouse cells maintained in culture at 38.5 degrees C, or its inefficient replication in nonneural tissues in vivo. Kinetic experiments tracing the virus through the nervous system after footpad inoculation showed that KOS was blocked at the level of the spinal ganglia. A cosmid library of strain 17 syn+ was utilized in recombination and in vivo selection experiments with strain KOS to establish the genomic region involved in 17 syn+ neuroinvasiveness. A cosmid clone containing the HindIII A fragment (0.25 to 0.53 map units) of strain 17 syn+ in mixed transfections with full-length KOS DNA yielded recombinants with enhanced neuroinvasiveness.

In an attempt to define the nature of the difference in the susceptibility of C57BL/6 (resistant) and A/J (susceptible) mice to herpes simplex virus type 1, we initiated a study of virus progression through the nervous system. After inoculation of virus in a rear footpad, C57BL/6 mice were found to be more than 500-fold more resistant, but resistance did not extend to pseudorabies virus. In additional investigations, it was found that the virus was selectively restricted at the level of spinal ganglia in C57BL/6 mice. No intrinsic difference in the ability of this tissue from either mouse strain to replicate virus was found. However, by 4 days after infection, morphological investigations indicated that a mononuclear cell infiltrate was present surrounding infected neurons and satellite cells both earlier and in greater numbers in the ganglia of C57BL/6 mice. Immunohistochemical methods showed that most of these cells did not express Thy 1.2 antigen, but the vast majority bore immunoglobulin G. The mechanism by which these infiltrating cells could restrict virus spread is discussed.

The results of a survey of 116 epileptic patients treated by monotherapy with phenytoin, carbamazepine and sodium valproate are described. No significant correlations were found between memory performance and serum anticonvulsant levels. However, correlations were found between memory performance and levels of red cell folate. The hypothesis that phenytoin may impair memory performance through the reduction of folate is discussed.