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BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.

Description of the subject. This research note discusses the results of measurements of particulate matter concentrations inside a pig fattening facility. Objectives. The objectives of the present study were to investigate the correlations between the different size fractions of indoor particulate matter (PM) inside a pig fattening facility and to investigate the evolution of particle size distribution (PSD) through a fattening period and between two housing systems and two cleaning protocols. Method. Data from two consecutive fattening periods in a commercial pig barn were used. Results. Very high correlations were found between PM10 and PM2.5 indoor concentrations. Depending on the measuring instrument, high or low correlations were found between PM1 and PM10 or PM2.5 indoor concentrations. No differences in PSD could be found between the two housing systems or the two cleaning protocols. Conclusions. The results from the present study showed high correlations between the indoor concentrations of PM10 and PM2.5. In the present study, no differences in PSD were found.

Climate change has rapidly altered marine ecosystems and is expected to continue to push systems and species beyond historical baselines into novel conditions. Projecting responses of organisms and populations to these novel environmental conditions often requires extrapolations beyond observed conditions, challenging the predictive limits of statistical modeling capabilities. Bioenergetics modeling provides the mechanistic basis for projecting climate change effects on marine living resources in novel conditions, has a long history of development, and has been applied widely to fish and other taxa. We provide our perspective on 4 opportunities that will advance the ability of bioenergetics-based models to depict changes in the productivity and distribution of fishes and other marine organisms, leading to more robust projections of climate impacts. These are (1) improved depiction of bioenergetics processes to derive realistic individual-level response(s) to complex changes in environmental conditions, (2) innovations in scaling individual-level bioenergetics to project responses at the population and food web levels, (3) more realistic coupling between spatial dynamics and bioenergetics to better represent the local- to regional-scale differences in the effects of climate change on the spatial distributions of organisms, and (4) innovations in model validation to ensure that the next generation of bioenergetics-based models can be used with known and sufficient confidence. Our focus on specific opportunities will enable critical advancements in bioenergetics modeling and position the modeling community to make more accurate and robust projections of the effects of climate change on individuals, populations, food webs, and ecosystems.

The placenta supports the metabolic and respiratory requirements of the fetus. Placental disorders, caused by various pathophysiological mechanisms, may result in adverse pregnancy and neonatal outcomes. Knowledge gaps remain in the understanding, reporting and interpretation of placental pathology relating to clinical conditions. This project aimed to collaboratively identify the most important unanswered research questions related to placental pathology. An international Priority Setting Partnership (PSP) was conducted, involving (perinatal) pathologists, obstetricians, paediatrician-neonatologists, midwives, and scientists with expertise in placental pathology. In the first survey, participants identified their three most important unanswered research questions. Afterwards literature was reviewed for evidence on the proposed questions. In a second survey, participants ranked the most important questions from an initial long-list. The top-ranked questions were then discussed and finalized in a 1-h online consensus workshop. Ninety participants completed the first survey. The majority of stakeholders were perinatal pathologists (n = 39 (43.3 %) and most were based in Europe (n = 43 (47.8 %). 270 questions were submitted; after review, these were subdivided into 32 overarching questions. The second ranking survey was completed by 53 participants. Twenty-five participants attended the online workshop, which reached consensus on the top 10. The questions focus, among others, on causes, recurrence risk, consistency of reporting, diagnosing tools and potential use of artificial intelligence. Following this international PSP, the top 10 prioritized research questions on placental pathology have been identified. This will inform the research agenda for funders and policy-makers, and is intended to improve care for patients suffering from placental insufficiency. • In this international Priority Setting Partnership, consensus was reached on the top 10 prioritized research questions on placental pathology. •Topics include causes of placental lesions, recurrence risk, consistency in reporting, diagnostic tools and the potential role of artificial intelligence. •The prioritized research questions will inform the research agenda, funders and policymakers, accelerating research on placental pathology. [ABSTRACT FROM AUTHOR]

Placental pathology lesions are common in early-onset fetal growth restriction (eoFGR). Therapeutic interventions to improve eoFGR outcomes are needed. In the international STRIDER trials (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) sildenafil didn't improve perinatal outcomes of eoFGR. We aimed to study the underlying placental pathology in the Dutch STRIDER trial and the effects of sildenafil on placental histopathology by describing the associations with sildenafil treatment, placental-dysfunction serum biomarkers and markers of oxidative stress. The Dutch STRIDER trial was a randomized controlled trial of sildenafil versus placebo in 216 singleton pregnancies complicated by eoFGR, included between 20+0- and 29+6-weeks' gestation. In 158 cases, placental histology was available. Lesions were classified independently by three perinatal pathologists blinded for clinical data, according to the international criteria of the Amsterdam Placental Workshop Group Consensus Statement. Blood samples taken at inclusion were analyzed for free thiols (FT), placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1, n = 85). The 'big four' placental lesions (maternal and fetal vascular malperfusion, and chronic or acute inflammatory lesions) were equally distributed in both groups. However, massive perivillous fibrin deposition (MPFD) and chronic histiocytic intervillositis (CHIV) were less common in the sildenafil-treated group compared to the placebo-treated group (p = 0.026 and p = 0.043). FT, PlGF and sFlt-1 at inclusion were not discriminative for placental lesions. Sildenafil had no effect on common placental lesions. The lower incidence of MPFD and CHIV after sildenafil exposure merits more research on the interaction between sildenafil and the immune system. • Sildenafil had no effect on the 'big four' placental lesions (maternal and fetal vascular malperfusion, and chronic or acute inflammatory lesions). • A lower occurrence of the rare placental lesions MPFD and CHIV were seen in cases with sildenafil compared to placebo. • Lower levels of FT at inclusion were not indicative of more severe placental pathology. • In this cohort, MVM is associated with a lower PLGF level and higher sFLT-1 level, which would be expected with placental insufficiency. [ABSTRACT FROM AUTHOR]

Background: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)--and associated prognostic factors--in meningioma and pituitary adenoma (PA) patients. Methods: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using onclinical and orthoptic examinations, which were performed every 3--4 months until palsy recovery, or at 18 months follow-up. Results: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P, 0.001). No significant protective or risk factors for recovery rate or time were identified. Conclusions: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs. [ABSTRACT FROM AUTHOR]

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Early utero-placental vascular development impacts placental development and function throughout pregnancy. We investigated whether impaired first-trimester utero-placental vascular development is associated with pathologic features of the postpartum placenta. In this prospective observational study of 65 ongoing pregnancies, we obtained three-dimensional power Doppler ultrasounds of the placenta at 7, 9 and 11 weeks of gestation. We applied VOCAL software to measure placental volume (PV), virtual reality based segmentation to measure utero-placental vascular volume (uPVV) and applied a skeletonization algorithm to generate the utero-placental vascular skeleton (uPVS). Vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-, crossing- or vessel point). Following delivery, placentas were measured and histologically examined according to the Amsterdam criteria to assess maternal vascular malperfusion (MVM). We used linear mixed models to estimate trajectories of PV, uPVV and uPVS development. Multivariable linear regression analysis with adjustments for confounders was used to evaluate associations between PV, uPVV and uPVS development and features of the postpartum placenta. We observed no associations between first-trimester PV development and measurements of the postpartum placenta. Increased first-trimester utero-placental vascular development, reflected by uPVV (β = 0.25 [0.01; 0.48]), uPVS end points (β = 0.25 [0.01; 0.48]), bifurcation points (β = 0.22 [0.05; 0.37]), crossing points (β = 0.29 [0.07; 0.52]) and vessel points (β = 0.09 [0.02; 0.17]) was positively associated with the postpartum placental diameter. uPVV was positively associated with postpartum placental weight. No associations were found with MVM. Development of the first-trimester utero-placental vasculature is associated with postpartum placental size, whereas placental tissue development contributes to a lesser extent. [Display omitted] • New imaging markers of early placental vascular development using 3D power Doppler. • Placental vascular imaging markers and histologic evaluation of the human placenta. • First-trimester vascular development is associated with postpartum placental size. [ABSTRACT FROM AUTHOR]

circumvallate placenta, placental abruption and acute chorioamnionitis separately are associated with unfavourable clinical outcomes. We aimed to determine the prevalence and define whether an association exists between the three abnormalities. 16,042 placenta pathology reports between 1997 and 2020 from a tertiary care centre in the Netherlands were retrospectively analysed. For the statistical analysis, the chi-square test and bootstrapping were used to evaluate an association. In our cohort the prevalence of circumvallate placenta is 2.2 %, placental abruption cases 4.0 % and acute chorioamnionitis 20.6 %. We observed a statistically significant association between all three placental abnormalities: circumvallate placenta, placental abruption and acute chorioamnionitis. In addition, there was also an association between circumvallate placenta and acute chorioamnionitis. Our results show that combined presence of circumvallate placenta, placental abruption and acute chorioamnionitis are associated in preterm birth (p = 0.001). A remarkable finding is that the combination of all three abnormalities (circumvallate placenta, placental abruption and acute chorioamnionitis) was not observed in term pregnancies >37 weeks. • Prevalence of circumvallate placenta 2.2 %, abruption 4.0 %, chorioamnionitis 20.6 %. • Significant association of all three abnormalities combined. • Association between circumvallate placenta and chorioamnionitis. • Combination of all three abnormalities was not observed pregnancies >37 wks. [ABSTRACT FROM AUTHOR]