Differences in Breastfeeding Duration by Maternal HIV Status: A Pooled Analysis of Nationally Representative Surveys in Sub-Saharan Africa.

BACKGROUND: Breastfeeding improves child survival but is a source of mother-to-child HIV transmission among women with unsuppressed HIV infection. Estimated HIV incidence in children is sensitive to breastfeeding duration among mothers living with HIV (MLHIV). Breastfeeding duration may vary according to maternal HIV status. SETTING: Sub-Saharan Africa. METHODS: We analyzed pooled data from nationally representative household surveys conducted during 2003-2019 that included HIV testing and elicited breastfeeding practices. We fitted survival models of breastfeeding duration by country, year, and maternal HIV status for 4 sub-Saharan African regions (Eastern, Central, Southern, and Western). RESULTS: Data were obtained from 65 surveys in 31 countries. In 2010, breastfeeding in the first month of life ("initial breastfeeding") among MLHIV ranged from 69.1% (95% credible interval: 68-79.9) in Southern Africa to 93.4% (92.7-98.0) in Western Africa. Median breastfeeding duration among MLHIV was the shortest in Southern Africa at 15.6 (14.2-16.3) months and the longest in Eastern Africa at 22.0 (21.7-22.5) months. By comparison, HIV-negative mothers were more likely to breastfeed initially (91.0%-98.7% across regions) and for longer duration (median 18.3-24.6 months across regions). Initial breastfeeding and median breastfeeding duration decreased during 2005-2015 in most regions and did not increase in any region regardless of maternal HIV status. CONCLUSIONS: MLHIV in sub-Saharan Africa are less likely to breastfeed initially and stop breastfeeding sooner than HIV-negative mothers. Since 2020, UNAIDS-supported HIV estimates have accounted for this shorter breastfeeding exposure among HIV-exposed children. MLHIV need support to enable optimal breastfeeding practices and to adhere to antiretroviral therapy for HIV treatment and prevention of postnatal mother-to-child transmission.

PET in vivo generators 134Ce and 140Nd on an internalizing monoclonal antibody probe.

The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.

Updates to Spectrum's case surveillance and vital registration tool for HIV estimates and projections.

INTRODUCTION: The Case Surveillance and Vital Registration (CSAVR) model within Spectrum estimates HIV incidence trends from surveillance data on numbers of new HIV diagnoses and HIV-related deaths. This article describes developments of the CSAVR tool to more flexibly model diagnosis rates over time, estimate incidence patterns by sex and age group and by key population group. METHODS: We modelled HIV diagnosis rate trends as a mixture of three factors, including temporal and opportunistic infection components. The tool was expanded to estimate incidence rate ratios by sex and age for countries with disaggregated reporting of new HIV diagnoses and AIDS deaths, and to account for information on key populations such as men who have sex with men (MSM), males who inject drugs (MWID), female sex workers (FSW) and females who inject drugs (FWID). We used a Bayesian framework to calibrate the tool in 71 high-income or low-HIV burden countries. RESULTS: Across countries, an estimated median 89% (interquartile range [IQR]: 78%-96%) of HIV-positive adults knew their status in 2019. Mean CD4 counts at diagnosis were stable over time, with a median of 456 cells/µl (IQR: 391-508) across countries in 2019. In European countries reporting new HIV diagnoses among key populations, median estimated proportions of males that are MSM and MWID was 1.3% (IQR: 0.9%-2.0%) and 0.56% (IQR: 0.51%-0.64%), respectively. The median estimated proportions of females that are FSW and FWID were 0.36% (IQR: 0.27%-0.45%) and 0.14 (IQR: 0.13%-0.15%), respectively. HIV incidence per 100 person-years increased among MSM, with median estimates reaching 0.43 (IQR: 0.29-1.73) in 2019, but remained stable in MWID, FSW and FWID, at around 0.12 (IQR: 0.04-1.9), 0.09 (IQR: 0.06-0.69) and 0.13% (IQR: 0.08%-0.91%) in 2019, respectively. Knowledge of HIV status among HIV-positive adults gradually increased since the early 1990s to exceed 75% in more than 75% of countries in 2019 among each key population. CONCLUSIONS: CSAVR offers an approach to using routine surveillance and vital registration data to estimate and project trends in both HIV incidence and knowledge of HIV status.

Estimating and projecting the number of new HIV diagnoses and incidence in Spectrum's case surveillance and vital registration tool.

OBJECTIVE: The Joint United Nations Programme on HIV/AIDS-supported Spectrum software package is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with case surveillance and vital registration data, such as historical trends in the number of newly diagnosed infections or AIDS-related deaths. This article describes development and application of the case surveillance and vital registration (CSAVR) tool for the 2019 estimate round. METHODS: Incidence in CSAVR is either estimated directly using single logistic, double logistic, or spline functions, or indirectly via the 'r-logistic' model, which represents the (log-transformed) per-capita transmission rate using a logistic function. The propensity to get diagnosed is assumed to be monotonic, following a Gamma cumulative distribution function and proportional to mortality as a function of time since infection. Model parameters are estimated from a combination of historical surveillance data on newly reported HIV cases, mean CD4 at HIV diagnosis and estimates of AIDS-related deaths from vital registration systems. Bayesian calibration is used to identify the best fitting incidence trend and uncertainty bounds. RESULTS: We used CSAVR to estimate HIV incidence, number of new diagnoses, mean CD4 at diagnosis and the proportion undiagnosed in 31 European, Latin American, Middle Eastern, and Asian-Pacific countries. The spline model appeared to provide the best fit in most countries (45%), followed by the r-logistic (25%), double logistic (25%), and single logistic models. The proportion of HIV-positive people who knew their status increased from about 0.31 [interquartile range (IQR): 0.10-0.45] in 1990 to about 0.77 (IQR: 0.50-0.89) in 2017. The mean CD4 at diagnosis appeared to be stable, at around 410 cells/µl (IQR: 224-567) in 1990 and 373 cells/µl (IQR: 174-475) by 2017. CONCLUSION: Robust case surveillance and vital registration data are routinely available in many middle-income and high-income countries while HIV seroprevalence surveillance and survey data may be scarce. In these countries, CSAVR offers a simpler, improved approach to estimating and projecting trends in both HIV incidence and knowledge of HIV status.

135La as an Auger-electron emitter for targeted internal radiotherapy.

135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 ± 19 MBq µA-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the 135La with an effective molar activity of 70 ± 20 GBq µmol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.

Improvements in Spectrum's fit to program data tool.

OBJECTIVE: The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round. METHODS: In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty. RESULTS: The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better. CONCLUSION: Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

Cyclotron produced 44gSc from natural calcium.

(44g)Sc was produced by 16MeV proton irradiation of unenriched calcium metal with radionuclidic purity greater than 95%. The thick target yield at saturation for (44g)Sc was 213 MBq/µA, dwarfing the yields of contaminants (43)Sc,(44 m)Sc, (47)Sc and (48)Sc for practical bombardment times of 1-2h. Scandium was isolated from the dissolved calcium target by filtration, and reconstituted in small volumes of dilute HCl. Reactions with the chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) indicated a reactivity of 54 ± 14 Gbq/µmol at end-of-bombardment.

Very high specific activity 66/68Ga from zinc targets for PET.

This work describes the production of very high specific activity (66/68)Ga from (nat)Zn(p,n) and (66)Zn(p,n) using proton irradiations between 7 and 16 MeV, with emphasis on (66)Ga for use with common bifunctional chelates. Principal radiometallic impurities are (65)Zn from (p,x) and (67)Ga from (p,n). Separation of radiogallium from target material is accomplished with cation exchange chromatography in hydrochloric acid solution. Efficient recycling of Zn target material is possible using electrodeposition of Zn from its chloride form, but these measures are not necessary to achieve high specific activity or near-quantitative radiolabeling yields from natural targets. Inductively coupled plasma mass spectroscopy (ICP-MS) measures less than 2 ppb non-radioactive gallium in the final product, and the reactivity of (66)Ga with common bifunctional chelates, decay corrected to the end of irradiation, is 740 GBq/µmol (20 Ci/µmol) using natural zinc as a target material. Recycling enriched (66)Zn targets increased the reactivity of (66)Ga with common bifunctional chelates.

Cross sections of the 36Ar(d,α)34mCl, 40Ar(d,α)38Cl, and 40Ar(d,p)41Ar nuclear reactions below 8.4 MeV.

We have measured the cross section for production of the medically interesting isotope (34m)Cl, along with (38)Cl and (41)Ar, using deuteron bombardments of (36)Ar and (40)Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas.

WE-C-217BCD-04: Multimodality Imaging of Breast Cancer Experimental Lung Metastasis.

PURPOSE: Metastatic breast cancer (MBC) is incurable. The clinical gold standard for assessing tumor microvessel density (MVD), an independent prognostic marker in MBC, is CD 105 staining. The goal of this study is to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging of CD105 expression in MBC (i.e. non-invasive measurement of MVD), as well as other applications such as early detection of metastasis, intraoperative guidance, etc. METHODS: TRC105, a chimeric anti-CD105 mAb, was dual-labeled with a NIRF dye and 89 Zr to yield 8 9 Zr-Df-TRC105-800CW. Luciferase-transfected 4T1 murine breast cancer cells were injected intravenously into female BALB/c mice to establish a lung MBC model. Bio luminescence imaging (BLI) was carried out to non- invasively monitor the lung tumor burden. Comprehensive in vivo/ex vivo studies were performed to investigate 8 9 Zr-Df-TRC105-800CW in this MBC model. Cetuximab was used as an isotype-matched control. RESULTS: Radiolabeled TRC105 has high tumor uptake in many tumor types in addition to MBC (e.g. pancreatic/prostate cancer and brain tumor), revealing broad clinical potential for TRC105-based agents. FACS analysis of HUVECs showed no difference in CD 105 binding between TRC105 and Df- TRC105-800CW. PET imaging revealed that 4T1 lung tumor uptake of 89 Zr-Df-TRC105-800CW was 8.7±1.4,10.9±0.5, and 9.7±1.1 %ID/g at 4, 24, and 48 h post-injection (n = 4), with excellent tumor contrast. Bio distribution studies, blocking, control studies with 8 9 Zr-Df-cetuximab- 800CW, ex vivo BLI/PET/NIRF imaging, and histology all confirmed CD 105 specificity of the tracer. NIRF imaging-guided removal of 4T1 tumors with Df-TRC105-800CW in a subcutaneous model was also straightforward. CONCLUSIONS: We report the first PET/NIRF imaging of CD105 expression in a MBC model. Broad clinical potential of TRC105- based agents was shown in many tumor types, which also enabled early detection of small metastases and provided intraoperative guidance for tumor removal.

[Pharmaco-economic aspects of perioperative pain management]. / Les aspects pharmacoéconomiques dans la gestion de la douleur périopératoire.

We present a reflection on pharmaco-economy of perioperative pain management. A real optimisation of expenses could be obtained if taking into consideration factors that augment and diminish costs of the process, due to the organisation of the process itself, due to optimisation of the information and decision's circuits. The cost of an analgesic is not significant when compared with the cost of entire process of pain management.

A superconducting beta spectrometer.

We have designed and constructed a superconducting beta spectrometer with a momentum resolution of about 2% and a peak solid angle of 0.5 sr. The performance of the spectrometer is described and the results of calibrations with line sources are presented.

Nonequilibrium functional renormalization group for interacting quantum systems.

We propose a nonequilibrium version of functional renormalization within the Keldysh formalism by introducing a complex-valued flow parameter in the Fermi or Bose functions of each reservoir. Our cutoff scheme provides a unified approach to equilibrium and nonequilibrium situations. We apply it to nonequilibrium transport through an interacting quantum wire coupled to two reservoirs and show that the nonequilibrium occupation induces new power law exponents for the conductance.

Effects of a branched p-nonylphenol isomer (4(3',6'-dimethyl-3'-heptyl)-phenol) on embryogenesis in Lymnae stagnalis L.

The tertiary branched alkyl-chain isomers of p-nonylphenol (NP) are perceived to have more estrogenic potency than its constituent secondary and primary straight alkyl-chain isomers. Investigations with single tertiary branched isomers of NP can therefore contribute toward the elucidation of the mechanisms of toxicity and estrogenicity of NP. A single tertiary branched alkyl-chain isomer (4(3',6'-dimethyl-3'-heptyl)-phenol) was used in studies to determine its effects on embryonic growth and mortality in Lymnaea stagnalis L. Egg masses were exposed to the test compound for 20 days in a static waterborne-exposure regime with an average NP concentration of 105 microg/L and water temperature range of 18-20 degrees C. Observations were made under a microscope and pictures were taken with a digital camera to determine the various developmental stages of growth, the duration of growth in each stage, embryo hatchability, and embryo mortality. The isomer was found to cause significant delay in all stages of growth and more significantly in the Morula and Veliger stages. An increase in embryo mortality, from the third day until the end of the experiment, was observed in exposed egg masses compared to controls. The hatching success of embryos was also significantly reduced by exposure, with 81% hatchability in exposed egg masses compared to 93% in the controls, after 18 days of continuous exposure. The encapsulating jelly strand that completely covers the rows of egg masses may have prevented the isomer residues from effectively penetrating into the embryos as shown by the observed low bioconcentration factors of the isomer in egg masses during exposure, resulting in unexpectedly lower observed estrogenic effects. However, this factor was not investigated. In vivo biotransformation of some of the residues of the isomer into catechol metabolites by the embryos during exposure could also result in the reduction of its estrogenic potential. To understand more fully the extent of toxicity and estrogenicity of this isomer, in vitro estrogenic assays are recommended. It would also be necessary to investigate its estrogenic effects on embryo development after in vivo maternal exposure.

In vivo metabolism and organ distribution of a branched 14C-nonylphenol isomer in pond snails, Lymnaea stagnalis L.

The branched isomers of p-nonylphenol (NP) are perceived to be more resistant to biodegradation in aquatic environments as well as to have more estrogen-like toxicity than the straight chain isomers. By use of GC-MS, some of them have been identified and found to exist in higher concentrations in the isomeric compound mixture than the straight chain isomers. The investigations of the distribution and metabolism of these branched isomers in aquatic organisms are therefore considered to be important in understanding the mechanisms of toxicity of NP. A single tertiary isomer of NP, 4(3'-,6'-dimethyl-3'-heptyl)-phenol, was synthesized in the laboratory and used in in vivo studies of its organ distribution and metabolism in Lymnaea stagnalis L., following a constant exposure of the organisms to 14C-NP isomer in water over a period of 8 days at an average exposure concentration of 105 ppb (range: 93-116 ppb). The results obtained clearly showed the distribution and bioconcentration of the isomer residues in various internal organs of Lymnaea after uptake in water and food. Analysis of the extracts of the organ tissues and faeces by HPLC and GC-MS after digestion with Pankreatin/beta-glucuronidase and nitric acid, respectively, showed that the isomer was metabolized by conjugation to glucuronic acid and hydroxylation to a catechol. The findings from these studies and their implications in the biotransformation and estrogenicity of NP in Lymnaea stagnalis L. are further discussed in detail in this paper.

Reproduction disturbances of Brachionus calyciflorus (rotifer) for the screening of environmental endocrine disrupters.

Rotifers and especially the Brachionus calyciflorus species have already shown advantages (e.g. good sensitivity, simplicity, ecological relevance, short generation time) for the chronic toxicity assessment of water pollutants. In this study, the B. calyciflorus three-day test was evaluated on ethinylestradiol, nonylphenol and testosterone for the determination of endocrine disrupting (reproductive) effects. Reproduction (intrinsic rate of population increase) and sex ratio (males/females and mictic females/amictic females) were explored and discussed as suitable endpoints. B. calyciflorus has shown a fair sensitivity to detect reproductive disrupting effects after exposure to ethinylestradiol, nonylphenol and testosterone. Population growth (intrinsic rate of population increase, r) and the ratio ovigerous females/ non-ovigerous females are both suitable endpoints, whereas the occurrence of males was not frequent enough to be used as endpoint.

Bisphosphonates are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase.

We report the cloning and sequencing of a gene encoding the farnesyl pyrophosphate synthase of Trypanosoma cruzi. The protein (T. cruzi farnesyl pyrophosphate synthase, TcFPPS) is an attractive target for drug development, since the growth of T. cruzi is inhibited by carbocation transition state/reactive intermediate analogs of its substrates, the nitrogen-containing bisphosphonates currently in use in bone resorption therapy. The protein predicted from the nucleotide sequence of the gene has 362 amino acids and a molecular mass of 41.2 kDa. Several sequence motifs found in other FPPSs are present in TcFPPS. Heterologous expression of TcFPPS in Escherichia coli produced a functional enzyme that was inhibited by the nitrogen-containing bisphosphonates alendronate, pamidronate, homorisedronate, and risedronate but was less sensitive to the non-nitrogen-containing bisphosphonate etidronate, which, unlike the nitrogen-containing bisphosphonates, does not affect parasite growth. The protein contains a unique 11-mer insertion located near the active site, together with other sequence differences that may facilitate the development of novel anti-Chagasic agents.

Main problems of the Russian Orlan-M space suit utilization for EVAs on the ISS.

In the recent years the Russian Orlan-M space suits have been improved as applied to their operational requirements for the ISS. A special attention is paid to enhancement of EVA crew efficiency and safety. The paper considers the main problems regarding specific features of the Russian space suit operation in the ISS, and analyses measures on their solution. In particular, the problems associated with the following are considered: enhancement of the anthropometric range for the EVA crewmembers; use of some US EMU elements and unified NASA equipment elements; Orlan-M operation support in the wide range of the ISS thermal conditions; use of Simplified Aid For Extravehicular activity Rescue (SAFER) designed as a self-rescue device, which will be used for an EVA crewmember return in the event that he (she) breaks away inadvertently from the ISS surface. The paper states the main space suit differences with reference to solution of the above problems. The paper presents briefly the design of space suit arms developed for crewmembers with small anthropometric parameters, as well as peculiarities and test results for the gloves with enhanced thermal protection. Measures on further space suit development with the purpose to improve its performances are considered.

Evaluation of results for Schirmer tear tests conducted with and without application of a topical anesthetic in clinically normal dogs of 5 breeds.

OBJECTIVE: To evaluate, for clinically normal dogs, results of Schirmer tear tests in eyes without topical anesthetic (STT) and to detect differences associated with breed, sex, age, day, and time of day in eyes in which STT was performed after use of topical anesthetic (STTa). ANIMALS: 41 Beagles, 43 Labrador Retrievers, 25 Golden Retrievers, 26 English Springer Spaniels, and 22 Shetland Sheepdogs. PROCEDURE: Beagles had STT and STTa values measured twice daily for 5 days. Client-owned dogs of 4 other breeds had STT and STTa values measured once. RESULTS: Mean +/- SD values of Beagles for STT and STTa were 20.2 +/- 2.5 and 3.8 +/- 2.7 mm/min. Mean values for STT and STTa were as follows: Labrador Retriever, 22.9 +/- 4.1 and 9.6 +/- 3.8 mm/min; English Springer Spaniel; 20.7 +/- 3.2 and 5.4 +/- 3.4 mm/min; Golden Retriever, 21.8 + 3.7 and 8.8 +/- 3.1 mm/min; and Shetland Sheepdog, 15.8 +/- 1.8 and 3.6 +/- 2.8 mm/min. Overall mean values for STT and STTa were 20.2 +/- 3.0 and 6.2 +/- 3.1 mm/min. Differences for STT and STTa were detected among breeds, but significant differences were not associated with sex or age within each breed or in overall values for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results for the STT reported here compare favorably with reported values, except for results of Shetland Sheepdogs; however, results for the STTa differ dramatically from reported values. Clinicians should consider effects attributable to breed when evaluating results of STT and STTa in dogs.

Intraocular melanoma in an alpaca.

A case of primary intraocular melanoma in an alpaca is reported. This patient also presented with a mild normocytic, normochromic anemia and hypoproteinemia. These can be markers of an immunodeficiency syndrome associated with llamas. Although this patient did not appear to have clinical signs of this syndrome, its presence needed to be ruled out as animals affected with this syndrome are subject to recurrent severe debilitating diseases and death. To our knowledge, intraocular melanoma has not been previously reported in an alpaca.