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Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365. All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine. No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. NCT02218125.

Secretary of Labor Elizabeth Dole has declared war against those who violate child labor laws. While her leadership should be commended, much more needs to be done if the interests of education and work are to be balanced in the lives of young people. Dole's strike has caught child labor exploiters off guard. Service sector employers of young people have been put on notice that the federal government is no longer willing to tolerate the abuses that are increasingly pervasive in our fast-paced society. Already, according to news accounts, the service sector is maneuvering to change child labor regulations. Any changes should be approved only after careful analysis and consideration of the facts. Dole's action has effectively expanded the enforcement of child labor laws to a new category of exploitation. Enforcement resources previously had been deployed to stop exploitation in places like garment-district sweatshops in large cities. The new category is the convenience-driven service industry-especially fast food operators, convenience stores and service stations. Dole's initiative could not come at a more opportune time.

Gene therapy with elivaldogene autotemcel (eli-cel) consisting of autologous CD34+ cells transduced with lentiviral vector containing complementary DNA (Lenti-D) has shown efficacy in clinical studies for the treatment of cerebral adrenoleukodystrophy. However, the risk of oncogenesis with eli-cel is unclear. We performed integration-site analysis, genetic studies, flow cytometry, and morphologic studies in peripheral-blood and bone marrow samples from patients who received eli-cel therapy in two completed phase 2-3 studies (ALD-102 and ALD-104) and an ongoing follow-up study (LTF-304) involving the patients in both ALD-102 and ALD-104. Hematologic cancer developed in 7 of 67 patients after the receipt of eli-cel (1 of 32 patients in the ALD-102 study and 6 of 35 patients in the ALD-104 study): myelodysplastic syndrome (MDS) with unilineage dysplasia in 2 patients at 14 and 26 months; MDS with excess blasts in 3 patients at 28, 42, and 92 months; MDS in 1 patient at 36 months; and acute myeloid leukemia (AML) in 1 patient at 57 months. In the 6 patients with available data, predominant clones contained lentiviral vector insertions at multiple loci, including at either (MDS and EVI1 complex protein EVI1 [ecotropic virus integration site 1], in 5 patients) or (positive regulatory domain zinc finger protein 16, in 1 patient). Several patients had cytopenias, and most had vector insertions in multiple genes within the same clone; 6 of the 7 patients also had somatic mutations ( , , , or , or ), and 1 of the 7 patients had monosomy 7. Of the 5 patients with MDS with excess blasts or MDS with unilineage dysplasia who underwent allogeneic hematopoietic stem-cell transplantation (HSCT), 4 patients remain free of MDS without recurrence of symptoms of cerebral adrenoleukodystrophy, and 1 patient died from presumed graft-versus-host disease 20 months after HSCT (49 months after receiving eli-cel). The patient with AML is alive and had full donor chimerism after HSCT; the patient with the most recent case of MDS is alive and awaiting HSCT. Hematologic cancer developed in a subgroup of patients who were treated with eli-cel; the cases are associated with clonal vector insertions within oncogenes and clonal evolution with acquisition of somatic genetic defects. (Funded by Bluebird Bio; ALD-102, ALD-104, and LTF-304 ClinicalTrials.gov numbers, NCT01896102, NCT03852498, and NCT02698579, respectively.).

Cannabis is the most prevalently used psychoactive substance in the United States. Cannabis has conflicting federal and state legal status in the US, however medical and recreational cannabis use are increasing. When assessing health outcomes, cannabis use classification has been modeled largely as current use status (never/former/current) or cumulative use (joint-years). These methods do not describe longitudinal patterns of use which may have unique relationships with health outcomes. We used cannabis use data spanning 30 years from the Coronary Artery Risk Development in Young Adults Cohort (CARDIA) to create trajectories of current cannabis use during young and middle adulthood. We identified 5 unique patterns of the probability of cannabis use during young and middle adulthood in the CARDIA Cohort. To support the cannabis probability trajectories, we qualitatively examined cumulative cannabis use as joint-years for each trajectory group. Trajectory group 5 had high probability of consistent cannabis use (0.8–0.9% probability of use) and had the highest number of joint-years (0.6 +/− 0.4). Trajectory group 1 who had a lower probability of cannabis use (0.05–0% probability of use) with the lowest number of joint-years (0.1 +/− 0.1).

Early-life adversity (ELA) is a risk factor for internalizing psychopathology (IP). ELA is also linked to alterations in neural phenotypes of emotion processing and maladaptive emotion regulatory strategies, such as ruminative brooding, in adulthood. We therefore expected that ELA would predict cortical brain activation to emotional faces in transdiagnostic IP and in turn, mediate the extent of rumination amongst patients with IPs and ELA (IP + ELA). One hundred and thirty-two individuals, including 102 treatment-seeking adults with heterogeneous IPs and 30 healthy controls (HCs) performed an Emotional Face-Matching Task during functional magnetic resonance imaging. Whole-brain analyses compared HC (n = 30), IP (n = 52), and IP + ELA (n = 50) neural responses to emotional (angry, fearful, happy, and sad) faces v. shapes, controlling for depression and anxiety symptoms. Parameter estimates of activation were extracted for significant between-group differences and tested as a mediator of ruminative brooding in IP + ELA. IP + ELA demonstrated increased activation in the superior frontal gyrus and anterior cingulate cortex (fear), superior parietal lobule, precuneus, posterior cingulate, and inferior temporal gyrus (fear only), and cuneus (fear and angry). These regions were preferentially correlated with ruminative brooding in IP + ELA, many of which mediated the link between IP + ELA and ruminative brooding. Results provide evidence that ELA history amongst IP patients augments engagement of brain regions involved in emotion processing, above and beyond what is accounted for by current symptoms. Though longitudinal designs are needed, alterations in the neural correlates of maladaptive processing of socio-emotional information may be a common pathway by which ELA poses risk for psychopathology.

The mesodermal germ layer is patterned into mediolateral subtypes by signaling factors including BMP and FGF. How these pathways are integrated to induce specific mediolateral cell fates is not well understood. We used mesoderm derived from post-gastrulation neuromesodermal progenitors (NMPs), which undergo a binary mediolateral patterning decision, as a simplified model to understand how FGF acts together with BMP to impart mediolateral fate. Using zebrafish and mouse NMPs, we identify an evolutionarily conserved mechanism of BMP and FGF-mediated mediolateral mesodermal patterning that occurs through modulation of basic helix-loop-helix (bHLH) transcription factor activity. BMP imparts lateral fate through induction of Id helix loop helix (HLH) proteins, which antagonize bHLH transcription factors, induced by FGF signaling, that specify medial fate. We extend our analysis of zebrafish development to show that bHLH activity is responsible for the mediolateral patterning of the entire mesodermal germ layer.

Linking health care for a mother and her baby promotes greater efficiency, lower costs, reduces duplication of resources, and maximises the effect on their health and survival in the same way investments in family planning and reproductive health improve health and wellbeing of women and their children.8 The investment case is strong, since the return on investment includes not only averted deaths (maternal, newborn, and stillbirth), but also improved child neurodevelopmental outcomes and reduced maternal morbidities.9 There have long been calls to integrate maternal and newborn baby health priorities.

Progress This paper is a narrative review that takes stock of the progress in addressing preterm birth over the past decade – notably on policies, national plans, innovation, evidence, social mobilisation, and community engagement – to inform future progress on preterm birth. At the global policy level, many countries have strongly supported collective initiatives and resolutions on maternal and newborn health relevant to preterm birth in multilateral fora, most recently through a World Health Assembly resolution calling for a revival amongst the global community on stalled progress for maternal, newborn and child health. Following the adoption of other global plans, like the Every Newborn Action Plan and Strategies for Ending Preventable Maternal Mortality, most countries set corresponding national mortality and coverage targets, and many have national and subnational policies and plans for integrated maternal and newborn health. Adequate financing remains a challenge, and sexual and reproductive health and rights of women and girls are being challenged globally. There have been significant advances in evidence-based interventions for preterm birth prevention and care, reflected in updated World Health Organization guidelines on antenatal, intrapartum and postpartum care, and care for small and sick newborns. The past decade has also seen progress in social mobilisation and community engagement, particularly parent groups and healthcare professional organisations advocating on issues surrounding preterm birth. Polycrisis and vulnerability There are, however, significant challenges that continue to hamper progress on preterm birth. Polycrisis – the interplay of overlapping economic, geopolitical, and environmental crises – compounds existing inequities, especially in places where health systems are already weak. Distinct and overlapping threats from conflict, climate change and the cost-of-living crisis present life-or-death challenges to those already facing extreme vulnerability, particularly women and girls, and small and sick newborns. Preterm birth: a marker of maternal and neonatal health progress in the coming decade The detrimental impacts of preterm birth are felt along the life course and across generations. The success of countries and the global community in preventing preterm births and ensuring high-quality care for mothers and preterm babies serves as a critical measure of progress – or failure – in advancing global efforts to improve maternal and newborn health. Plain language summary Countries have agreed on global plans and resolutions to improve maternal and newborn health. The World Health Assembly recently emphasized the need for renewed efforts in this area. Many countries have set national goals, but implementation remains a challenge as does funding. There have been advances in evidence-based interventions for preterm birth prevention and care, reflected in updated World Health Organization guidelines. Progress has also been made in community engagement, with parent groups and healthcare organisations as leading advocates. However, overlapping crises hinder progress, including conflicts, climate change, pandemics, and the cost-of-living crisis. These crises increase inequities and pose serious risks to women and newborns, especially where health systems are weak. Preterm birth is an important indicator of progress on maternal and neonatal health. How well countries and the global community address preterm birth and provide care for mothers and babies will show their overall success or failure in improving maternal and newborn health more broadly. Key findings • Over the past decade, global and national policy frameworks, targets and plans relevant to preterm birth have been adopted, though significant funding gaps remain. •  Knowledge of ‘what works’ to prevent and delay preterm birth and to care for babies who are born preterm has improved and is reflected in updated World Health Organization technical guidelines. •  The world has flatlined on preterm birth prevention resulting in renewed urgency to learn from and fully leverage knowledge gained over the past decade to accelerate progress in the next decade. •  Overlapping and compounding challenges of climate change, conflict, pandemics and the cost-of-living crisis pose significant direct and indirect risks for pregnant women and preterm babies and must be mitigated. •  Addressing preterm birth is a key component of integrated maternal and newborn health across the continuum of care and along the life course, and a key marker of progress.

(1) Background: Integrated standardized patient examinations (ISPEs) allow students to demonstrate competence with curricular learning and communication. Digital recordings of these experiences provide an objective permanent record, allowing students to review and improve their performance. Although recordings have been utilized as a tool in physical therapy education, no studies have described the impact of reviewing recordings of ISPE. This qualitative pilot study aimed to investigate student perceptions and learning after reviewing their recordings of ISPE. (2) Methods: Second-year Doctor of Physical Therapy students (n= 23) participated in the study by completing an anonymous online survey after reviewing their recordings from three ISPEs. Thematic analysis was used to identify codes and central themes from the survey data. (3) Results: The results showed that 95.6% of students found the video review process beneficial. Five themes emerged: (i) digital recordings provide an objective performance assessment, (ii) approaches to self-review vary, (iii) it provides an opportunity for growth, (iv) a holistic review is possible, and (v) students need structure and guidance in the process. (4) Conclusions: Study findings indicate that a review of the recordings of ISPEs facilitates the development of clinical skills for physical therapy students. Implementing an explicit framework for reviewing the recordings may enhance the process and facilitate further promotion of reflection-on-action.