Rapid Establishment of a Biospecimen Resource To Study the Global Impact of COVID-19 Vaccines.

The emergence and explosive spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 highlighted the need to rapidly develop curated biobanks to inform the etiology, diagnosis, and treatment options for global outbreaks of communicable diseases. Recently, we undertook efforts to develop a repository of biospecimens from individuals aged 12 and older who were to be vaccinated against coronavirus disease 19 (COVID-19) with vaccines developed with support from the United States Government. We planned to establish 40 or more clinical study sites in at least six countries to collect biospecimens from 1,000 individuals, 75% of whom were to be SARS-CoV-2 naive at the time of enrollment. Specimens would be used to (i) ensure quality control of future diagnostic tests, (ii) understand immune responses to multiple COVID-19 vaccines, and (iii) provide reference reagents for the development of new drugs, biologics, and vaccines. Biospecimens included serum, plasma, whole blood, and nasal secretions. Large-volume collections of peripheral blood mononuclear cells (PBMCs) and defibrinated plasma were also planned for a subset of subjects. Participant sampling was planned at intervals prior to and following vaccination over a 1-year period. Here, we describe the selection of clinical sites for specimen collection and processing, standard operating procedure (SOP) development, design of a training program for tracking specimen quality, and specimen transport to a repository for interim storage. This approach allowed us to enroll our first participants within 21 weeks from the study's initiation. Lessons learned from this experience should benefit the development of biobanks in response to future global epidemics. IMPORTANCE The ability to rapidly create a biobank of high-quality specimens in response to emergent infectious diseases is critical to allow for the development of prevention and treatment, as well as to effectively monitor the spread of the disease. In this paper, we report on a novel approach to getting global clinical sites up and running within a short time frame and to monitor the quality of specimens collected to ensure their value in future research efforts. Our results have important implications for the monitoring of the quality of biospecimens collected and to design effective interventions to address shortcomings, where needed.

Combining hippocampal volume metrics to better understand Alzheimer's disease progression in at-risk individuals.

To date nearly all clinical trials of Alzheimer's disease (AD) therapies have failed. These failures are, at least in part, attributable to poor endpoint choice and to inadequate recruitment criteria. Recently, focus has shifted to targeting at-risk populations in the preclinical stages of AD thus improved predictive markers for identifying individuals likely to progress to AD are crucial to help inform the sample of individuals to be recruited into clinical trials. We focus on hippocampal volume (HV) and assess the added benefit of combining HV and rate of hippocampal atrophy over time in relation to disease progression. Following the cross-validation of previously published estimates of the predictive value of HV, we consider a series of combinations of HV metrics and show that a combination of HV and rate of hippocampal atrophy characterises disease progression better than either measure individually. Furthermore, we demonstrate that the risk of disease progression associated with HV metrics does not differ significantly between clinical states. HV and rate of hippocampal atrophy should therefore be used in tandem when describing AD progression in at-risk individuals. Analyses also suggest that the effects of HV metrics are constant across the continuum of the early stages of the disease.

Knowledge, attitudes and behaviour regarding the infant oral health visit: are dentists in Ireland aware of the recommendation for a first visit to the dentist by age 1 year?

AIM: To assess the knowledge, attitudes and behaviour of dentists nationwide in Ireland regarding the infant oral health visit, and also to elucidate whether dentists were aware of the recommendation for a first dental visit by age 1 year and of what care should be provided at this visit. METHODS: A validated 10-item questionnaire was distributed to a representative sample of non-paediatric dentists (non-PDs) and paediatric dentists (PDs) practicing in Ireland. The questionnaire focused on respondents' demographics in addition to their knowledge, attitudes and behaviour regarding the infant dental visit. RESULTS: Seventy-three percent of non-PDs reported seeing patients aged 0-36 months. Compared to all PD respondents, 58% of non-PDs believed that the first dental visit should occur by age 1 year. Furthermore, non-PDs provided the same care as PDs at the infant dental visit, with the exception of evaluating for fluoride needs and placing fluoride varnish. The main barrier to early oral healthcare was reported to be parents not requesting dental appointments for their infants. CONCLUSIONS: There remains a need to increase the proportion of non-PDs in Ireland seeing infants by their first birthday. It is recommended that Irish undergraduate and continuing education courses incorporate clinical training regarding the infant oral health visit and emphasise fluoride needs evaluation and fluoride varnish application. Additionally, a nationwide health promotion initiative is indicated to inform parents of the importance of a dental visit by age 1 year.

Mangrove Sedimentation and Response to Relative Sea-Level Rise.

Mangroves occur on upper intertidal shorelines in the tropics and subtropics. Complex hydrodynamic and salinity conditions, related primarily to elevation and hydroperiod, influence mangrove distributions; this review considers how these distributions change over time. Accumulation rates of allochthonous and autochthonous sediment, both inorganic and organic, vary between and within different settings. Abundant terrigenous sediment can form dynamic mudbanks, and tides redistribute sediment, contrasting with mangrove peat in sediment-starved carbonate settings. Sediments underlying mangroves sequester carbon but also contain paleoenvironmental records of adjustments to past sea-level changes. Radiometric dating indicates long-term sedimentation, whereas measurements made using surface elevation tables and marker horizons provide shorter perspectives, indicating shallow subsurface processes of root growth and substrate autocompaction. Many tropical deltas also experience deep subsidence, which augments relative sea-level rise. The persistence of mangroves implies an ability to cope with moderately high rates of relative sea-level rise. However, many human pressures threaten mangroves, resulting in a continuing decline in their extent throughout the tropics.

Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization.

UNLABELLED: The potency and breadth of the recently isolated neutralizing human monoclonal antibodies to HIV-1 have stimulated interest in their use to prevent or to treat HIV-1 infection. Due to the antigenically diverse nature of the HIV-1 envelope (Env), no single antibody is highly active against all viral strains. While the physical combination of two broadly neutralizing antibodies (bNAbs) can improve coverage against the majority of viruses, the clinical-grade manufacturing and testing of two independent antibody products are time and resource intensive. In this study, we constructed bispecific immunoglobulins (IgGs) composed of independent antigen-binding fragments with a common Fc region. We developed four different bispecific IgG variants that included antibodies targeting four major sites of HIV-1 neutralization. We show that these bispecific IgGs display features of both antibody specificities and, in some cases, display improved coverage over the individual parental antibodies. All four bispecific IgGs neutralized 94% to 97% of antigenically diverse viruses in a panel of 206 HIV-1 strains. Among the bispecific IgGs tested, VRC07 × PG9-16 displayed the most favorable neutralization profile. It was superior in breadth to either of the individual antibodies, neutralizing 97% of viruses with a median 50% inhibitory concentration (IC50) of 0.055 µg/ml. This bispecific IgG also demonstrated in vivo pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for the prevention and treatment of HIV-1 infection in humans. IMPORTANCE: To prevent or treat HIV-1 infection, antibodies must potently neutralize nearly all strains of HIV-1. Thus, the physical combination of two or more antibodies may be needed to broaden neutralization coverage and diminish the possibility of viral resistance. A bispecific antibody that has two different antibody binding arms could potentially display neutralization characteristics better than those of any single parental antibody. Here we show that bispecific antibodies contain the binding specificities of the two parental antibodies and that a single bispecific antibody can neutralize 97% of viral strains with a high overall potency. These findings support the use of bispecific antibodies for the prevention or treatment of HIV-1 infection.

Variable nutrient stoichiometry (carbon:nitrogen:phosphorus) across trophic levels determines community and ecosystem properties in an oligotrophic mangrove system.

Our study investigated the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of mangrove island of the Mesoamerican Barrier Reef (Twin Cays, Belize). The C:N:P of abiotic and biotic components of this oligotrophic ecosystem was measured and served to build networks of nutrient flows for three distinct mangrove forest zones (tall seaward fringing forest, inland dwarf forests and a transitional zone). Between forest zones, the stoichiometry of primary producers, heterotrophs and abiotic components did not change significantly, but there was a significant difference in C:N:P, and C, N, and P biomass, between the functional groups mangrove trees, other primary producers, heterotrophs, and abiotic components. C:N:P decreased with increasing trophic level. Nutrient recycling in the food webs was highest for P, and high transfer efficiencies between trophic levels of P and N also indicated an overall shortage of these nutrients when compared to C. Heterotrophs were sometimes, but not always, limited by the same nutrient as the primary producers. Mangrove trees and the primary tree consumers were P limited, whereas the invertebrates consuming leaf litter and detritus were N limited. Most compartments were limited by P or N (not by C), and the relative depletion rate of food sources was fastest for P. P transfers thus constituted a bottleneck of nutrient transfer on Twin Cays. This is the first comprehensive ecosystem study of nutrient transfers in a mangrove ecosystem, illustrating some mechanisms (e.g. recycling rates, transfer efficiencies) which oligotrophic systems use in order to build up biomass and food webs spanning various trophic levels.

A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma.

BACKGROUND: We investigated cytokines and angiogenic factors (CAFs) in patients with metastatic renal cell carcinoma (mRCC) treated in a randomized phase II clinical trial of sorafenib versus sorafenib+ interferon-α (IFN-α) that yielded no differences in progression-free survival (PFS). We aimed to link the CAF profile to PFS and select candidate predictive and prognostic markers for further study. METHODS: The concentrations of 52 plasma CAFs were measured pretreatment (n = 69), day 28, and day 56 using multiplex bead arrays and enzyme-linked immunosorbent assay. We investigated the association between baseline levels of CAFs with PFS and posttreatment changes. RESULTS: Unsupervised CAF clustering analysis revealed two distinct mRCC patient groups with elevated proangiogenic or proinflammatory mediators. A six-marker baseline CAF signature [osteopontin, vascular endothelial growth factor (VEGF), carbonic anhydrase 9, collagen IV, VEGF receptor-2, and tumor necrosis factor-related apoptosis-inducing ligand] correlated with PFS benefit (hazard ratio 0.20 versus 2.25, signature negative versus positive, respectively; P = 0.0002). While changes in angiogenic factors were frequently attenuated by the sorafenib+ IFN combination, most key immunomodulatory mediators increased. CONCLUSIONS: Using CAF profiling, we identified two mRCC patient groups, a candidate plasma signature for predicting PFS benefit, and distinct marker changes occurring with each treatment. This platform may provide valuable insights into renal cell carcinoma biology and the molecular consequences of targeted therapies.

Biocomplexity in mangrove ecosystems.

Mangroves are an ecological assemblage of trees and shrubs adapted to grow in intertidal environments along tropical coasts. Despite repeated demonstration of their economic and societal value, more than 50% of the world's mangroves have been destroyed, 35% in the past two decades to aquaculture and coastal development, altered hydrology, sea-level rise, and nutrient overenrichment. Variations in the structure and function of mangrove ecosystems have generally been described solely on the basis of a hierarchical classification of the physical characteristics of the intertidal environment, including climate, geomorphology, topography, and hydrology. Here, we use the concept of emergent properties at multiple levels within a hierarchical framework to review how the interplay between specialized adaptations and extreme trait plasticity that characterizes mangroves and intertidal environments gives rise to the biocomplexity that distinguishes mangrove ecosystems. The traits that allow mangroves to tolerate variable salinity, flooding, and nutrient availability influence ecosystem processes and ultimately the services they provide. We conclude that an integrated research strategy using emergent properties in empirical and theoretical studies provides a holistic approach for understanding and managing mangrove ecosystems.

Recommendations for promoting the engagement of older people in activities to prevent falls.

OBJECTIVE: To develop recommendations for promoting uptake of and adherence to falls-prevention interventions among older people. DESIGN: The recommendations were initially developed from literature review, clinical experience of the core group members, and substantial qualitative and quantitative studies of older people's views. They were refined through a consultation process with members of the falls-prevention community, drawing on Delphi survey and nominal group techniques. Transparency was enhanced by recording and reporting aspects of the iterative consultation process such as the degree of consensus and critical comments on drafts of the recommendations. SETTING: The recommendations were developed and refined at three meetings of the core group, and through internet-based consultation and two meetings involving members of the wider falls-prevention community. PARTICIPANTS: The authors developed the recommendations incorporating the feedback from the researchers and practitioners responding to a broad-based internet consultation and consulted in the meetings. RESULTS: A high degree of consensus was achieved. Recommendations addressed the need for public education, ensuring that interventions were compatible with a positive identity, tailoring interventions to the specific situation and values of the individual, and using validated methods to maintain longer-term adherence. CONCLUSION: These recommendations represent a consensus based on current knowledge and evidence, but the evidence base from which these recommendations were developed was limited, and not always specific to prevention of falls. To increase the effectiveness of falls-prevention interventions, further research is needed to identify the features of falls-prevention programmes that will encourage older people's engagement in them.

Breed, gender and neutering status of British dogs with anal sac gland carcinoma.

This study details the breed, gender and neutering status of a large cohort of British canine patients suffering from histologically confirmed anal sac gland carcinoma. Estimates of the relative risk for the development of this disease attributable to these factors are calculated. To reduce the impact of sampling errors, cases were selected from veterinary histopathology laboratories rather than referral hospital databases, and multiple estimates of the general British canine population were used. The weaknesses of the statistical assumptions made are discussed. There was no evidence to support a gender predisposition for the development of this condition. English cocker spaniels are significantly over-represented, with a mean relative risk estimate of 7.3. The mean relative risk estimate associated with being neutered was 1.4; the effect of neutering appeared to be more significant in male dogs compared with that in female dogs.

Psychosocial benefits of solitary reminiscence writing: an exploratory study.

Claims have been made that reminiscence has benefits for older people's psychological well-being, and that writing memories may be a therapeutic process. This paper describes an exploratory study in which five nursing home residents engaged in a process of writing their memories by themselves, in a series of booklets containing memory prompts and photographs, over a period of four weeks. Each completed booklet was typed up by researchers and returned to participants the following week, with a bound copy provided to participants at the end of the study period. Analysis focuses on two sets of data: an in-depth case study of one participant, and a thematic analysis of field notes, researcher reflections, and the written material produced by the other study participants. The case study revealed three main themes: views on the past; sharing the past; and confidence in writing about the past. The field note analysis indicated the presence of four themes: proof and maintenance of skills; psychological or internal processes; social contact; and pleasure in reminiscence. The writing was seen as cathartic and provided a meaningful purpose, an opportunity to exercise writing skills and memory, and a focus for participants to share key stories with others. This exploratory study suggests that there is potential in using solitary writing within a reminiscence framework to improve psychological well-being in older people. However, caution should be exercised when encouraging older people to write their stories. Issues of confidentiality, audience, support, and appropriateness of the activity for the individual need consideration.

Preference among female Army recruits for use of self-administrated vaginal swabs or urine to screen for Chlamydia trachomatis genital infections.

BACKGROUND: Use of self-administered vaginal swabs (SAS) for the detection of Chlamydia trachomatis by nucleic acid amplification tests simplifies specimen collection and transport, especially for women in nonclinical settings. GOAL: We investigated the preference and comfort level of military women for the collection of SAS, compared with urine, for the diagnosis of genital chlamydial infections. STUDY DESIGN: During March through August 1999, female Army recruits in basic training at Fort Jackson, South Carolina, were invited to participate in the study. Participants were requested to complete a questionnaire after providing both first-void urine (FVU) and SAS specimens. Participant characteristics, preferences, and comfort levels were assessed using multivariate logistic regression. RESULTS: From 4496 eligible female recruits, 1403 (31%) completed questionnaires and 1382 provided both specimens; 11.8% (166 of 1403) of participants were infected with chlamydia. The relative sensitivity and specificity of the C. trachomatis Ligase Chain Reaction test on SAS in 1382 matched pairs was 81.1% and 98.6%, respectively, using the test result on urine specimens as the comparison standard. Most of the participants (90.8%) reported that they felt comfortable collecting the FVU specimen, and 69.6% indicated that they felt comfortable collecting SAS. Either specimen collection type received high acceptability at home and in the field, and more women reported that they would collect FVU than reported they would collect SAS in the future (in the field: FVU: 79.4%, SAS: 68.8%, P <0.001); at home: FVU: 90.9%, SAS: 82.9%, P <0.001). When questioned about ease of use, 60.4% of women reported that urine was the easier method. Preferences for SAS were associated with being white and having had sexual risk behaviors in the past 3 months. CONCLUSION: A study of preferences for urine versus self-administered vaginal swabs for the detection of C. trachomatis in military women showed that women generally found SAS acceptable. SAS should be a feasible alternative to urine collection in situations in which specimen storage or transport is an issue.

CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors.

CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface-bound ectopeptidase with important roles in T-cell activation and tumour biology. We now report that CD26/DPPIV enhances sensitivity to apoptosis induced by the antineoplastic agents doxorubicin and etoposide. In particular, CD26/DPPIV presence is associated with increased susceptibility to the mitochondrial pathway of apoptosis, documented by enhanced cleavage of poly (ADP ribose) polymerase (PARP), caspase-3 and caspase-9, Bcl-xl, and Apaf-1, as well as increased expression of death receptor 5 (DR5). We also show that the caspase-9-specific inhibitor z-LEHD-fmk inhibits drug-mediated apoptosis, leading to decreased PARP and caspase-3 cleavage, and reduced DR5 expression. Importantly, through detailed studies that demonstrate the association between topoisomerase II alpha expression and DPPIV activity, our data provide further evidence of the key role played by CD26 in biological processes.

The COPE index--a first stage assessment of negative impact, positive value and quality of support of caregiving in informal carers of older people.

Data was collected in five countries from informal carers of older people (n = 577) via a common protocol. Carers completed: (1) a 17-item version of the Carers of Older People in Europe (COPE) Index, an assessment of carers' perceptions of their role : (2) a questionnaire on demographic and caregiving circumstances : and (3) three instruments included for the criterion validation of the COPE Index (the General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the World Health Organization Quality of Life-BREF). Principal Component Analysis of the COPE Index was followed by internal consistency analysis of emergent components. Scales derived by summing items loading on the components were analyzed for their association with the criterion measures. Two components, negative impact and positive value, emerged consistently across countries. A third component, quality of support was less consistent across countries. Scales derived from the negative impact and positive value components were internally consistent and significantly associated with the criterion validity measures. These two scales and four items drawn from the quality of support component were retained in the final COPE Index. While further testing is required, the COPE Index has current utility in increasing understanding of the role perceptions of carers of older people.

Fear of falling, falls efficacy, and health outcomes in older people following hip fracture.

PURPOSE: This study sought to determine whether fear of falling and falls efficacy independently contribute to the prediction of health outcomes after a fall, controlling for length of stay in hospital, prefall activity problems, and history of falls. METHOD: Eighty-two older people (> or = 65 years) admitted to hospital as a result of a fall, with proximal femoral fracture, were interviewed to assess variables of interest. At two months after initial interview, participants (n = 57) were re-interviewed in their own home, and their functional limitation and further fall events were assessed. Regression analyses were carried out to determine the ability of the variables assessed in hospital to predict functional limitation and further falls post discharge. RESULTS: Perceived risk of falling and falls efficacy did not explain variance in functional limitation when added to a model containing biomedical factors. In the prediction of further falls, addition of falls efficacy and worry over further falls to a model containing biomedical factors resulted in a statistically reliable improvement, although falls efficacy was not independently associated with outcome. CONCLUSIONS: Assessing worry over further falls in hospital may help to identify older people with hip fracture at risk of poor health outcomes.

Geographic epidemiology of gonorrhoea and chlamydia on a large military installation: application of a GIS system.

OBJECTIVES: The geographic epidemiology of infectious diseases can help in identifying point source outbreaks, elucidating dispersion patterns, and giving direction to control strategies. We sought to establish a geographic information system (GIS) infectious disease surveillance system at a large US military post (Fort Bragg, North Carolina) using STDs as the initial outcome for the model. METHODS: Addresses of incident cases were plotted onto digitised base maps of Fort Bragg (for on-post addresses) and surrounding Cumberland County, NC (for off-post addresses) using MAPINFO Version 5. We defined 26 geographic sectors on the installation. Active duty soldiers attending the post preventive medicine clinic were enrolled between July 1998 and June 1999. RESULTS: Gonorrhoea (GC) was diagnosed in 210/2854 (7.4%) and chlamydia (CT) in 445/2860 (15.6%). African-American male soldiers were at higher risk for GC (OR = 4.6 (95% CL 3.0 to 7.2)) and chlamydia (OR = 2.0 (1.4 to 2.7)). For women, there were no ethnic differences in gonorrhoea prevalence, but chlamydia was higher in African-Americans (OR = 2.0 (1.4-2.7)). Rank and housing type were associated with gonorrhoea and chlamydia in men, but were not significant factors in women. For gonorrhoea, two geographic sectors had prevalences between 14.0%-16.5%, three between 10.3%-13.9%, three between 7.1%-10.2%, and five between 3.0%-7.1%. The geographic distribution demonstrated a core-like pattern where the highest sectors were contiguous and were sectors containing barracks housing lower enlisted grade personnel. In contrast, chlamydia prevalence was narrowly distributed. CONCLUSION: GIS based disease surveillance was easily and rapidly implemented in this setting and should be useful in developing preventive interventions.

Features of Chlamydia trachomatis and Neisseria gonorrhoeae infection in male Army recruits.

Non-health care-seeking male United States Army recruits were tested for Chlamydia trachomatis (n=2245) and Neisseria gonorrhoeae (n=884), using a urine ligase chain reaction test to determine prevalence and potential risk factors for infection. The prevalence of chlamydial infection was 5.3%. Black race, a new sex partner, a history of trichomonas, and the presence of symptoms were associated with chlamydial infection. The prevalence of N. gonorrhoeae infection was 0.6%. Only a reported history of or positive test for C. trachomatis was associated with gonorrheal infection. Of those testing positive for chlamydia, 14% reported symptoms versus 40% of those with gonorrhea. Younger age was not a predictor of either infection, as has been shown for women. A substantial number of male army recruits are infected with C. trachomatis, but few are infected with N. gonorrhoeae. Screening on the basis of symptoms alone would miss the majority of both infections.

Evaluation of use of a single intravaginal swab to detect multiple sexually transmitted infections in active-duty military women.

The accuracy and suitability of use of a single intravaginal swab (SIS) for polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and human papillomavirus infection was assessed in a cross-sectional study of 841 active-duty military women. The SIS, compared with standard diagnostic tests, allowed detection of more gonorrhea, more chlamydial infection, and more trichomoniasis. Sensitivity and specificity of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and 97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and 92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to those with cervical swabs tested for human papillomavirus. Assay of clinician-collected and self-collected SISs yielded prevalences similar to those of standard diagnostic tests for all sexually transmitted infections. Therefore, the use of SISs is acceptable for the simultaneous diagnosis of multiple sexually transmitted infections and has potential for use as a self-administered diagnostic tool with widespread applicability among women.

Diagnosis of human papillomavirus infection by dry vaginal swabs in military women.

OBJECTIVE: Human papillomavirus (HPV) assays are likely to be used with increasing frequency in clinical management of women with abnormal Papanicolaou smears and in cervical cancer screening. Our objective was to simplify the method of collection of female genital tract specimens. The utility of vaginal dry swabs for HPV diagnosis was evaluated. METHODS: Specimens for cytology and for HPV identification were collected by a clinician from 189 female soldiers attending a military clinic. Three methods of specimen collection for HPV identification were compared: a vaginal dry swab (v-DRY), and vaginal and cervical swabs placed into specimen transport medium (v-STM and c-STM). Swabs were shipped to a STD laboratory for processing. Specific HPV types were identified by a consensus primer based PCR based method. Results from 165 women were evaluable. RESULTS: HPV prevalence by the three methods was similar and ranged from 44.8% to 50.9%. 53 (32.1%) women were HPV positive and 60 (36.4%) women were HPV negative by all three collection methods. With respect to the risk categories of specific HPV types, there was greater agreement between the results from the two vaginal (v-DRY and v-STM) samples (kappa values of 0.69-0.81) than between the cervical (c-STM) and either of the vaginal samples (kappa values of 0.37-0.55). The HPV yield from c-STM was somewhat greater than that from the vaginal specimens but the correlation between cytological abnormalities and HPV was high for all three methods. CONCLUSION: A dry vaginal swab may be an acceptable method of specimen collection for HPV diagnosis.

Spiro(indoline-3,4'-piperidine) growth hormone secretagogues as ghrelin mimetics.

A series of small molecules derived from MK-0677, a potent synthetic GHS, mimicking the N-terminal Gly-Ser-O-(n-octanoyl)-L-Ser-Phe segment of ghrelin was synthesized and tested in a binding and in a functional assay measuring intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Replacement of Phe in this tetrapeptide with a spiro(indoline-3,4'-piperidine) group, Gly-Ser with 2-aminoisobutyric acid, and O-(n-octanoyl)-L-Ser with O-benzyl-D-Ser provided synthetic GHS agonists with similar functional potency as ghrelin.