Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Research Note: Relative bioavailability of zinc in zinc hydroxychloride for chicks.

A chick assay was conducted to determine the effects of Zn source on performance and to establish a Zn relative bioavailability value (RBV) for a new source of Zn hydroxychloride. In the assay, 8-day-old chicks were fed a Zn-deficient soy protein concentrate diet supplemented with 0, 7, and 15 mg Zn/kg from feed grade ZnSO4 monohydrate for 14 d to establish a standard response curve. The same basal diet was supplemented with 3, 7, and 10 mg Zn/kg from a new Zn hydroxychloride (SAMZn). A second source of Zn hydroxychloride (IBZn) was supplemented at 10 mg Zn/kg as a direct comparison to the highest level of SAMZn. Weight gain increased (P < 0.05) with increasing Zn level, regardless of source. Weight gain of chicks fed 7 mg Zn/kg from SAMZn was not different (P > 0.05) from chicks fed 15 mg Zn/kg from ZnSO4. Weight gain was not different (P > 0.05) when comparing the 2 sources of Zn hydroxychloride supplemented at 10 mg Zn/kg. Tibia ash Zn and total tibia Zn were increased (P < 0.05) by all Zn sources and responded linearly (P < 0.05) to Zn supplementation from ZnSO4 and SAMZn. Total tibia Zn concentration was not different (P > 0.05) for chicks fed 10 mg Zn/kg from either source of Zn hydroxychloride. Multiple linear regression of total tibia Zn on supplemental Zn intake (R2 = 0.95) resulted in a RBV of 115% for SAMZn compared with ZnSO4 (set at 100%). The RBV of SAMZn was higher (P < 0.05) than ZnSO4. In conclusion, relative bioavailability of Zn (based on tibia Zn) in Zn hydroxychloride from SAMZn was higher than feed grade ZnSO4 based on multiple regression slope-ratio analysis and was similar to that of IBZn Zn hydroxychloride based on tibia Zn responses to 10 mg/kg supplemental dietary Zn.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania.

BACKGROUND: Hypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500-2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (< 1000 mg elemental calcium/day) during pregnancy have also shown similar reductions in the risk of preeclampsia; however, no trials to date have directly compared low-dose to the standard high-dose calcium supplementation. Our objective is to assess the non-inferiority of low-dose as compared to standard high-dose calcium supplementation in pregnancy. METHODS/DESIGN: We will conduct two independent trials in Bangalore, India (n = 11,000 pregnancies), and Dar es Salaam, Tanzania (n = 11,000 pregnancies). The trial designs are individually randomized, parallel group, quadruple-blind, non-inferiority trials of low-dose calcium supplementation (500 mg elemental calcium/day) as compared to standard high-dose calcium supplementation (1500 mg elemental calcium/day) among nulliparous pregnant women. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized calcium regimen from randomization until the time of delivery. The co-primary outcomes are (i) preeclampsia and (ii) preterm birth; we will test non-inferiority of the primary outcomes for low-dose as compared to the standard high-dose supplementation regimen in each trial. The trials' secondary outcomes include gestational hypertension, severe features of preeclampsia, pregnancy-related death, third trimester severe anemia, fetal death, stillbirth, low birthweight, small-for-gestational age birth, and infant death. DISCUSSION: The trials will provide causal evidence on the non-inferiority of low-dose as compared to the standard high-dose supplementation in India and Tanzania. A single tablet, low-dose calcium supplementation regimen may improve individual-level adherence, reduce programmatic costs, and ultimately expand implementation of routine calcium supplementation in pregnancy in populations with low dietary calcium intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03350516 ; registered on 22 November 2018. Clinical Trials Registry-India identifier: CTRI/2018/02/012119 ; registered on 23 February 2018. Tanzania Medicines and Medical Devices Authority Trials Registry identifier: TFDA0018/CTR/0010/5 ; registered on 20 December 2018.

Prevention and treatment of malaria in pregnancy: what do pregnant women and health care workers in East India know and do about it?

BACKGROUND: Limited qualitative research has been performed in India to investigate views and behaviours of pregnant women regarding malaria despite the threat of malaria-related adverse maternal and neonatal outcomes. To address this gap, a comprehensive study on malaria prevention and treatment attitudes, knowledge and behaviour among pregnant women in India was conducted. METHODS: Pregnant women and healthcare workers (HCWs), encompassing clinic-based providers, traditional birth attendants, and auxiliary nurse-midwives were enrolled for in-depth interviews (IDIs) at 7 hospital sites and nearby communities in Jharkhand and Chhattisgarh States. Questions addressed health concerns and attitudes, knowledge and practices regarding malaria prevention and treatment; probing covered modern and traditional approaches. Data were analyzed using a thematic approach. RESULTS: A total of 83 pregnant women and 119 HCWs participated in 202 IDIs, 90 in Jharkhand and 112 in Chhattisgarh. A majority of Jharkhand respondents, but only one-fourth in Chhattisgarh, named malaria among top health issues for pregnant women. Just over half of pregnant women were willing to try new prevention methods (especially insecticide-treated bed nets), although cost-related barriers to such methods were stressed. Most respondents voiced concerns about malaria treatment during pregnancy, mainly citing potential harm to the baby. Most knew that mosquitoes transmitted malaria, but a substantial minority, including among HCWs, described incorrect transmission modes. Most knew a proven prevention method (usually bed nets or coils); a few knew other methods. A minority of pregnant women, but most HCWs, knew about malaria treatment, although some HCWs described unproven treatments. Most respondents described use of modern prevention methods in their communities, typically bed nets, although probing revealed irregular use. Half (especially in Jharkhand and particularly HCWs) described use of traditional prevention approaches such as burning leaves and rubbing oils on the body; traditional remedies for malaria treatment were common, and varied by site and population. CONCLUSIONS: Understanding of malaria varied as a concern for pregnant women, continued use of unproven malaria prevention and treatment strategies was evident in this population in India. These results highlight the need to educate both pregnant women and HCWs about effective malaria methods to protect pregnant women and their babies from malaria.

Functionality and acceptability of a wireless fetal heart rate monitoring device in term pregnant women in rural Southwestern Uganda.

BACKGROUND: Over 3 million stillbirths occur annually in sub Saharan Africa; most occur intrapartum and are largely preventable. The standard of care for fetal heart rate (FHR) assessment in most sub-Saharan African settings is a Pinard Stethoscope, limiting observation to one person, at one point in time. We aimed to test the functionality and acceptability of a wireless FHR monitor that could allow for expanded monitoring capacity in rural Southwestern Uganda. METHODS: In a mixed method prospective study, we enrolled 1) non-laboring healthy term pregnant women to wear the device for 30 min and 2) non-study clinicians to observe its use. The battery-powered prototype uses Doppler technology to measure fetal cardiotocographs (CTG), which are displayed via an android device and wirelessly transmit to cloud storage where they are accessible via a password protected website. Prototype functionality was assessed by the ability to obtain and transmit a 30-min CTG. Three obstetricians independently rated CTGs for readability and agreement between raters was calculated. All participants completed interviews on acceptability. RESULTS: Fifty pregnant women and 7 clinicians were enrolled. 46 (92.0%) CTGs were successfully recorded and stored. Mean scores for readability were 4.71, 4.71 and 4.83 (out of 5) with high agreement (intra class correlation 0.84; 95% CI 0.74 to 0.91). All pregnant women reported liking or really liking the device, as well as high levels of comfort, flexibility and usefulness of the prototype; all would recommend it to others. Clinicians described the prototype as portable, flexible, easy-to-use and a time saver. Adequate education for clinicians and women also seemed to improve correct usage and minimise concerns on safety of the device. CONCLUSIONS: This prototype wireless FHR monitor functioned well in a low-resource setting and was found to be acceptable and useful to both pregnant women and clinicians. The device also seemed to have potential to improve the experience of the users compared with standard of care and expand monitoring capacity in settings where bulky, wired or traditional equipment are unreliable. Further research needs to investigate the potential impact and cost of such innovations to improve perinatal outcomes.

Ghana randomized air pollution and health study (GRAPHS): study protocol for a randomized controlled trial.

BACKGROUND: Household air pollution exposure is a major health risk, but validated interventions remain elusive. METHODS/DESIGN: The Ghana Randomized Air Pollution and Health Study (GRAPHS) is a cluster-randomized trial that evaluates the efficacy of clean fuels (liquefied petroleum gas, or LPG) and efficient biomass cookstoves in the Brong-Ahafo region of central Ghana. We recruit pregnant women into LPG, efficient cookstove, and control arms and track birth weight and physician-assessed severe pneumonia incidence in the first year of life. A woman is eligible to participate if she is in the first or second trimester of pregnancy and carrying a live singleton fetus, if she is the primary cook, and if she does not smoke. We hypothesize that babies born to intervention mothers will weigh more and will have fewer cases of physician-assessed severe pneumonia in the first year of life. Additionally, an extensive personal air pollution exposure monitoring effort opens the way for exposure-response analyses, which we will present alongside intention-to-treat analyses. Major funding was provided by the National Institute of Environmental Health Sciences, The Thrasher Research Fund, and the Global Alliance for Clean Cookstoves. DISCUSSION: Household air pollution exposure is a major health risk that requires well-tested interventions. GRAPHS will provide important new evidence on the efficacy of both efficient biomass cookstoves and LPG, and will thus help inform health and energy policies in developing countries. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov on 13 April 2011 with the identifier NCT01335490 .

An integrated approach for vascular health: a call to action.

Vascular diseases such as stroke, myocardial infarction, most causes of heart failure, dementia, peripheral arterial disease, certain kidney, and many lung and eye conditions are a result of disorders in the blood vessels (large and small) throughout the entire human body. Vascular diseases are the leading cause of preventable death and disability in Canada. Most vascular diseases share common risk factors (high blood pressure, diabetes, dyslipidemia, and obesity), which can be influenced by modifiable health behaviours such as unhealthy diet, smoking, lack of physical activity, and stress. Ninety percent of Canadians face an increased risk, which could be modified by managing these health behaviours and risk factors. Canada's aging population, combined with alarming trends in obesity, physical inactivity, high blood pressure, and diabetes are expected to further increase the social and economic effect of vascular diseases in the coming decades, unless there are major changes in health policy. Even more concerning is the increase in vascular risk factors among Canada's youth, and ethnically diverse populations. Vascular diseases affect not only the patient, but also place burdens on their spouses, families, friends, and communities. Tremendous potential exists to reduce the effects of vascular diseases through healthy public policy, supporting Canadians to make healthy lifestyle changes, and coordinating efforts across the continuum of care in a patient-focused manner. Vascular health requires partnerships for action across many sectors including government, health care practitioners, academia, not-for-profit organizations, and the private sector. The health sector alone cannot solve this problem.

Molecular and phytochemical investigation of Angelica dahurica and Angelica pubescentis essential oils and their biological activity against Aedes aegypti, Stephanitis pyrioides, and Colletotrichum species.

In this study, Angelica dahurica and Angelica pubescentis root essential oils were investigated as pest management perspectives, and root samples were also analyzed genetically using the nuclear ribosomal internal transcribed spacer (ITS) region as a DNA barcode marker. A. pubescentis root essential oil demonstrated weak antifungal activity against Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides, whereas A. dahurica root essential oil did not show antifungal activity. Conversely, A. dahurica root essential oil demonstrated better biting deterrent and insecticidal activity against yellow fever mosquito, Aedes aegypti, and azalea lace bugs, Stephanitis pyrioides, than A. pubescentis root oil. The major compounds in the A. dahurica oil were found as α-pinene (46.3%), sabinene (9.3%), myrcene (5.5%), 1-dodecanol (5.2%), and terpinen-4-ol (4.9%). α-Pinene (37.6%), p-cymene (11.6%), limonene (8.7%), and cryptone (6.7%) were the major compounds found in the A. pubescentis oil. In mosquito bioassays, 1-dodecanol and 1-tridecanol showed antibiting deterrent activity similar to the positive control DEET (N,N-diethyl-3-methylbenzamide) at 25 nmol/cm(2) against Ae. aegypti, whereas only 1-tridecanol showed repellent activity in human-based cloth patch bioassay with minimum effective dosages (MED) of 0.086 ± 0.089 mg/cm(2) (DEET = 0.007 ± 0.003 mg/cm(2)). In larval bioassays, 1-tridecanol was more toxic with an LC50 value of 2.1 ppm than 1-dodecanol having an LC50 value of 5.2 ppm against 1-day-old Ae. aegypti larvae. 1-Dodecanol and 1-tridecanol could be useful for the natural mosquito control agents.

Insecticidal and biting deterrent activity of rose-scented geranium (Pelargonium spp.) essential oils and individual compounds against Stephanitis pyrioides and Aedes aegypti.

BACKGROUND: Rose-scented geranium, Pelargonium spp., essential oils from the cultivars 'Bourbon', 'China', 'Egypt', 'Rober's Lemon Rose' and 'Frensham' were analyzed by GC-FID and GC-MS. A total of 136 compounds were identified from five essential oils, constituting 85.5-99.7% of the oils. Essential oils and pure compounds were evaluated for their insecticidal activity against Stephanitis pyrioides and larvicidal and biting deterrent activity against Aedes aegypti. RESULTS: All five geranium oils were toxic to S. pyrioides, and four of these five were more potent than malathion and neem. Trans-nerolidol (LD50 = 13.4 ppm) was the most toxic compound against one-day-old Ae. aegypti larvae, followed by geraniol (49.3 ppm), citronellol (49.9 ppm) and geranyl formate (58.5 ppm). Essential oil of cultivar 'Egypt' at 100 µg cm(-2) [biting deterrent index (BDI) = 0.8] showed the highest biting deterrent activity, followed by cultivars 'Frensham' (BDI = 0.76), 'China' (BDI = 0.72), 'Rober's Lemon Rose' (BDI = 0.63) and 'Bourbon' (BDI = 0.45) essential oils. Among the pure compounds, the biting deterrent activity of geranic acid (BDI = 0.99) was not significantly different from that of N,N-diethyl-m-toluamide (DEET). CONCLUSION: Essential oils and pure compounds showed insecticidal activity against S. pyrioides and Ae. aegypti. The high biting deterrent activity of geranic acid points to the need for further research.

Antifungal and insecticidal activity of two Juniperus essential oils.

Essential oils of two Tibetan Junipers Juniperus saltuaria and J. squamata var. fargesii (Cupressaceae) were obtained by distilling dried leaves and branches using a Clevenger apparatus. Sixty-seven compounds from J. saltuaria and 58 from J. squamata var. fargesii were identified by gas chromatography-mass spectrometry (GC-MS). Both essential oils contained similar ratios of four abundant monoterpenoids: 44 and 35% sabinene, 13 and 9% elemol, 8 and 7% terpinen-4-ol, and 4 and 17% alpha-pinene, respectively. These oils had antifungal activity based on a direct bioautography assay of Colletotrichum acutatum, C. fragariae, and C. gloeosporioides, and insecticidal activity based on serial-time mortality bioassay of azalea lace bugs, Stephanitis pyrioides. Antifungal activity of Juniperus oils was weak when compared with commercial fungicides such as benomyl and captan. Whole Juniperus oils at quarter the dosage used against Colletotrichum species were more insecticidal than 10 mg/mL malathion, killing > or =70-90% adult lace bugs after 4 hours of exposure. Rf values of 0.18 for J. saltuaria oil and 0.19 for J. squamata oil indicated lipophilic monoterpenes which were the putative sources of biological activity.

In vitro analysis of the herbal compound Essiac.

BACKGROUND: Despite the recommendation of the Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative, little research has been published on the widely used herbal compound Essiac. We aimed to address this deficiency by conducting a series of assays to determine some of the purported activities of Essiac in vitro. MATERIALS AND METHODS: The activity of Essiac was measured using established assays to assess anti-oxidant, fibrinolytic, anti-microbial, anti-inflammatory, immune modulation, cell-specific cytotoxicity, and impact on cytochrome P450 (CYP450) enzyme pathways. RESULTS: Essiac exhibited significant antioxidant activity in the ABTS assay. A 20-fold dilution of Essiac also exhibited significant immunomodulatory effects, specifically through stimulation of granulocyte phagocytosis, increases in CD8+ cell activation, and moderately inhibiting inflammatory pathways. Essiac exhibited significant cell-specific cytotoxicity towards ovarian epithelial carcinoma cells (A2780). Importantly, a 20-fold dilution of Essiac showed significant inhibition of several CYP450 enzymes, most notably CYP1A2 (37%) and CYP2C19 (24%). Essiac demonstrated dose-dependent inhibition of clot fibrinolysis. CONCLUSION: In vitro analysis of Essiac indicates significant antioxidant and immunomodulatory properties, as well as neoplastic cell specific cytotoxicity consistent with the historical properties ascribed to this compound. Importantly, significant CYP450 and fibrinolysis inhibition were also observed. This is the first comprehensive investigation of the in vitro effects of Essiac.

An in vivo analysis of the herbal compound essiac.

BACKGROUND: Essiac is a herbal compound that has been in common use with cancer patients in North America for over 80 years. Despite its relatively widespread use, there are no peer-reviewed published reports of in vivo studies regarding the use of this compound. MATERIALS AND METHODS: Essiac was administered orally to test animals prior to all experiments. Standard assays to test protection from ethanol-induced gastric ulceration and carbon tetrachloride-induced hepatic injury were performed on Wistar rats. Assays of postglucose-load serum glucose and cellular and humoral immune modulation were conducted on ICR and BALB/C mice, respectively. RESULTS: Essiac demonstrated a modest gastric protective effect via reduction of ethanol-induced gastric ulceration. However, Essiac did not demonstrate significant hepatoprotective, hypoglycemic or immunomodulatory properties. CONCLUSION: Essiac, administered in established in vivo experimental models, did not significantly demonstrate its purported physiological modifying effects.

Universal access -- but when? Treating the right patient at the right time: access to electrophysiology services in Canada.

The Canadian Cardiovascular Society Access to Care Working Group has published a series of commentaries on access to cardiovascular care in Canada. The present article reviews the evidence for timely access to electrophysiology services. Using the best available evidence along with expert consensus by the Canadian Heart Rhythm Society, the panel proposed a series of benchmarks for access to the full scope of electrophysiology services, from initial consultation through to operative procedures. The proposed benchmarks are presented herein.

Insecticidal activity of 23 essential oils and their major compounds against adult Lipaphis pseudobrassicae (Davis) (Aphididae: Homoptera).

Essential oils from 23 species of plants comprising 14 genera and 4 plant families were obtained by Clevenger-type water distillation. The major compounds in these essential oils were identified with GC-MS and their insecticidal activity against adult turnip aphids, Lipaphis pseudobrassicae (Davis), tested with dosage-mortality bioassays. We examined mortality only for viviparous adults because sizeable aphid populations on crucifer (Brassicaceae) hosts are largely produced by these wingless, parthenogenic females. Twenty-two of the oils were directly applied to aphid females in randomized blocks at concentrations of 0.0, 1.0, 2.5, 5.0 and 10.0 mg ml(-1). Essential oils mixed with a non-toxic emulsifying agent, dimethyl sulfoxide (DMSO), more easily penetrated the waxy insect cuticle. Probit analysis and LC(50) at three different exposures showed aphids were quickly incapacitated and killed by aliphatic aldehydes, phenols and monocyclic terpenes contained in Bifora and Satureja oils and at applied concentrations as low as 0.3 to 1.0 mg ml(-1). Only enough Pimpinella isaurica oil and its three phenylpropanoid fractions were available for testing at a single concentration of 10 mg ml(-1). We could not spare any additional P. isaurica oil for testing at other concentrations. Phenylpropanoids isolated from P. isaurica oil when recombined or left naturally blended in the oil were highly bioactive against L. pseudobrassicae at 10 mg ml(-1).

Nectar robbery by bees Xylocopa virginica and Apis mellifera contributes to the pollination of rabbiteye blueberry.

Honey bees, Apis mellifera L., probe for nectar from robbery slits previously made by male carpenter bees, Xylocopa virginica (L.), at the flowers of rabbiteye blueberry, Vaccinium ashei Reade. This relationship between primary nectar robbers (carpenter bees) and secondary nectar thieves (honey bees) is poorly understood but seemingly unfavorable for V. ashei pollination. We designed two studies to measure the impact of nectar robbers on V. ashei pollination. First, counting the amount of pollen on stigmas (stigmatic pollen loading) showed that nectar robbers delivered fewer blueberry tetrads per stigma after single floral visits than did our benchmark pollinator, the southeastern blueberry bee, Habropoda laboriosa (F.), a recognized effective pollinator of blueberries. Increasing numbers of floral visits by carpenter bee and honey bee robbers yielded larger stigmatic loads. As few as three robbery visits were equivalent to one legitimate visit by a pollen-collecting H. laboriosa female. More than three robbery visits per flower slightly depressed stigmatic pollen loads. In our second study, a survey of 10 commercial blueberry farms demonstrated that corolla slitting by carpenter bees (i.e., robbery) has no appreciable affect on overall V. ashei fruit set. Our observations demonstrate male carpenter bees are benign or even potentially beneficial floral visitors of V ashei. Their robbery of blueberry flowers in the southeast may attract more honey bee pollinators to the crop.

Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines.

A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin receptor subtypes. The target compounds were evaluated using in vivo behavioral assays for hallucinogen-like and 5-HT(1A) agonist activity and in vitro radioligand competition assays for their affinity at 5-HT(2A), 5-HT(2C), and 5-HT(1A) receptor sites. Functional activity at the 5-HT(2A) receptor was determined for all compounds. In addition, for some compounds functional activity was determined at the 5-HT(1A) receptor. Hallucinogen-like activity, evaluated in the two-lever drug discrimination paradigm using LSD-trained rats, was attenuated or abolished for all of the fluorinated analogues. One of the tryptamines, 4-fluoro-5-methoxy-DMT (6), displayed high 5-HT(1A) agonist activity, with potency greater than that of the 5-HT(1A) agonist 8-OH-DPAT. The ED(50) of 6 in the two-lever drug discrimination paradigm using rats trained to discriminate the 5-HT(1A) agonist LY293284 was 0.17 micromol/kg, and the K(i) at [(3)H]8-OH-DPAT-labeled 5-HT(1A) receptors was 0.23 nM. The results indicate that fluorination of hallucinogenic tryptamines generally has little effect on 5-HT(2A/2C) receptor affinity or intrinsic activity. Affinity at the 5-HT(1A) receptor was reduced, however, in all but one example, and all of the compounds tested were full agonists but with reduced functional potency at this serotonin receptor subtype. The one notable exception was 4-fluoro-5-methoxy-DMT (6), which had markedly enhanced 5-HT(1A) receptor affinity and functional potency. Although it is generally considered that hallucinogenic activity results from 5-HT(2A) receptor activation, the present results suggest a possible role for involvement of the 5-HT(1A) receptor with tryptamines.

Strategic choices for medical group practices.

This is the sixth in a series of articles (1) describing how to identify, assess, diagnose and strategically manage key medical group practice (MGP) stakeholders and (2) interpreting the results from the Facing the Uncertain Future (FUF) study. This article continues (from the previous article in this series) the discussion of the vital strategic stakeholder management process of choosing the most effective strategies for key stake holders based on two strategic priorities: reducing stakeholders potential for threat and enhancing their potential for cooperation. From this critical strategic priority-setting process. strategies are classified as either involving, collaborating, defending, or monitoring. Using data from the FUF project, four medical group practice (MCP) stakeholders are analyzed. These are the integrated delivery system/network (lDS/N) itself as well as its components: physicians, hospitals and managed care organizations (MCOs). The FUF project's MGP executive respondents believe these four stakeholders will be some of the most important MGP stakeholders in the year 2000. The FUF study was conducted jointly between the Center for Research in Ambulatory Health Care Administration (CRAHCA), the research and development arm of the Medical Group Management Association (MGMA), Englewood. Colo., and The Institute for Management and Leadership Research (IMLR). College of Business Administration at Texas Tech University, Lubbock, Texas. MGMA s American College of Medical Practice Executives (ACMPE), faculty of Texas Tech University's Ph.D. and M.BA programs in Health Organization Management (HOM), and faculty from the University of Alabama at Birmingham collaborated on the project. Abbott Laboratories. Abbott Park. Ill., provided funding for the FUF project The administration of Round One was completed in the fall of 1994. The administration of Round Two was completed in the summer of 1995. Selected Round One (i.e.. health care experts) and Round Two (i.e., MGP executives) results have previously been presented in educational programs and publications.

The problematic fit of diagnosis and strategy for medical group stakeholders--including IDS/Ns.

This article extends stakeholder management theory using data from 270 medical practice executives to identify key stakeholders and determine the "fit" between stakeholder diagnosis and stakeholder management strategy. Four optimal and 12 suboptimal situations are identified.