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Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda.A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression.A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%).Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

The origin of calcium production in the first stars (Pop III stars), which formed out of the primordial matter of the Big Bang, and their fates, remain most fascinating mysteries in astrophysics. Advanced nuclear burning and supernovae were thought to be the dominant source of the Ca production seen in all stars. Here we report on a qualitatively different path to Ca production through break-out from the "warm" carbon-nitrogen-oxygen (CNO) cycle. We extend direct measurement of the $^{19}$F($p$, $\gamma$)$^{20}$Ne break-out reaction down to an unprecedentedly low energy point of 186 keV and discover a key resonance at 225 keV. In the domain of astrophysical interest, at around 0.1 giga kelvin, this thermonuclear $^{19}$F($p$,$\gamma$)$^{20}$Ne rate is up to a factor of 7.4 larger than the previous recommended rate. Our stellar models show a stronger break-out during stellar hydrogen burning than thought before, and may reveal the nature of Ca production in Pop III stars imprinted on the oldest known ultra-iron poor star, SMSS0313-6708. This result from the China Jinping Underground Laboratory, the deepest laboratory in the world, offering an environment with extremely low cosmic-ray induced background, has far-reaching implications on our understanding of how the first stars evolve and die. Our rate showcases the impact that faint Pop III star supernovae can have on the nucleosynthesis observed in the oldest known stars and first galaxies, key mission targets of the James Webb Space Telescope., Comment: 32 pages, 8 figures, 6 tables

The interplay and correlation between the $$^{22}$$ 22 Ne$$(\alpha ,\gamma )^{26}$$ ( α , γ ) 26 Mg and the competing $$^{22}$$ 22 Ne$$(\alpha ,n)^{25}$$ ( α , n ) 25 Mg reaction plays an important role for the interpretation of the $$^{22}$$ 22 Ne$$(\alpha ,n)^{25}$$ ( α , n ) 25 Mg reaction as a neutron source in the s- and n-processes. This paper provides a summary and new data on the $$\alpha $$ α -cluster and single-particle structure of the compound nucleus $$^{26}$$ 26 Mg and the impact on the reaction rate of these two competing processes in stellar helium burning environments.

Purpose 1.7 billion children lack access to surgical care, particularly in low- and middle-income countries (LMIC). The pediatric surgical workforce density (PSWD), an indicator of surgical access, correlates with survival of complex pediatric surgical problems. To determine if PSWD also correlates with population-level health outcomes for children, we compared PSWD with pediatric-specific mortality rates and determined the PSWD associated with improved survival. Methods Using medical licensing registries, pediatric surgeons practicing in 26 countries between 2015 and 2019 were identified. Countries’ PSWD was calculated as the ratio of pediatric surgeons per 100,000 children. The correlation between neonatal, infant and under 5 mortality rates and PSWD was assessed using Spearman’s correlations and piecewise linear regression models. Results Four LIC, eight L-MIC, ten UMIC and four HIC countries, containing 420 million children, were analyzed. The median PSWD by income group was 0.03 (LIC), 0.12 (L-MIC), 1.34 (UMIC) and 2.13 (HIC). PSWD strongly correlated with neonatal (0.78, p 0.37. Currently, PSWD in LMICs is inadequate to meet UN Sustainable Development Goal 3.2 for child mortality.

PURPOSE In describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development. METHODS We retrospectively reviewed all patients with BCR-ABL–positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test. RESULTS One hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days ( P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis ( P = .056) and imatinib initiation ( P = .170) was not significantly different. CONCLUSION Coupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

ObjectivesOlder adults under-enroll in early phase cancer clinical trials. There are limited data on their trial experiences, which hampers our ability to understand potential reasons and responses to under-enrollment. We aimed to explore older adults' experiences and deliberations with phase 1 trials.Materials and methodsWe analyzed 101 in-depth interviews with 39 adults (average 2.6 interviews per participant) about their experiences with phase 1 trials. All respondents were ≥ 65 years and had advanced cancer. Interviews lasted 60-90 min and were audio-recorded, transcribed, and analyzed to identify respondents' understanding of clinical research, perceptions of early phase trials, and experiences with enrollment.ResultsClinical trial participation was an interactive process that unfolded over time. Older adults relied on ongoing guidance and discussion with their oncologist to navigate the process. Respondents were generally interested in life-prolonging therapies, including enrollment in early phase clinical trials, but did not necessarily state this explicitly to their oncologist. While respondents did not mention age as a limitation to trials participation, participants age > 70 were less enthusiastic about participation and more often discussed their quality of life and weighed benefits of trial participation in the context of their remaining months of life.ConclusionEarly phase clinical trial enrollment is complex, and older adults rely on their oncologist to navigate this process. Acknowledging this complexity through shared decision-making may ensure that older adults have appropriate opportunities to enroll in early phase clinical trials and guard against inappropriate under-enrollment.

Proposed mechanisms for the production of calcium in the first stars (population III stars)-primordial stars that formed out of the matter of the Big Bang-are at odds with observations

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

We present a precise measurement of the asymptotic normalization coefficient (ANC) for the 16O ground state (GS) through the 12C(11B, 7Li)16O transfer reaction using the Quadrupole‐3‐Dipole (Q3D) magnetic spectrograph. The present work sheds light on the existing discrepancy of more than 2 orders of magnitude between the previously reported GS ANC values. This ANC is believed to have a strong effect on the 12C(α, γ)16O reaction rate by constraining the external capture to the 16O ground state, which can interfere with the high-energy tail of the 2+ subthreshold state. Based on the new ANC, we determine the astrophysical S-factor and the stellar rate of the 12C(α, γ)16O reaction. An increase of up to 21% in the total reaction rate is found within the temperature range of astrophysical relevance compared with the previous recommendation of a recent review. Finally, we evaluate the impact of our new rate on the pair-instability mass gap for black holes (BH) by evolving massive helium core stars using the MESA stellar evolution code. The updated 12C(α, γ)16O reaction rate decreases the lower and upper edges of the BH gap about 12% and 5%, respectively.

In the United States of America, government responses to the COVID-19 pandemic have brought into focus conflicts between public health activities and religious liberty. State and local governments utilized familiar and long-established public health measures to combat this pandemic, including surveillance, testing, reporting, contact tracing, sanitation, closure, isolation, quarantine, and social distancing.2 Closure orders have had significant effects on religious believers and their places of worship. In addition to disrupting regular worship assemblies, public health orders also disrupted other important religious services, including baptisms and Eucharistic celebrations, weddings and funerals, last rites and pastoral counseling, religious education and charitable works. Many jurisdictions enforced public health measures even-handedly against religious and secular institutions, and some state and municipal governments displayed attentive sensitivity to the unique concerns of faith communities. In some instances, however, governments adopted overly restrictive measures or enforced measures unequally against religious institutions. Litigation was instituted in many jurisdictions, with litigants bringing claims under federal and state law.3 Courts, including the United States Supreme Court, have issued rulings in many cases. This paper examines conflicts between public health orders and religious liberty that arose in the United States during the COVID-19 pandemic, and it argues that the strict-scrutiny standard, rather than the rational-basis standard or a com-parable standard, is the appropriate standard to protect religious liberty from infringement by government orders in the current public health crisis. It explores these conflicts by considering several of the judicial rulings. However, before turning to these cases, this paper considers several constitutional background issues and the public health enterprise. KEYWORDS: public health, measures, religious freedom, COVID-19 pandemic&nbsp

Products of the 5-lipoxygenase metabolic pathway may be important mediators of inflammation in canine skin. Pharmacologic blockade of this pathway may therefore decrease clinical signs associated with canine atopy. To test this hypothesis, 31 dogs were entered on a randomized, double-blind, placebo-controlled, crossover trial to assess the efficacy of an investigational oral 5-lipoxygenase inhibitor (WY-50295) in treating canine atopy. Dogs were treated for 11 days with the drug and 11 days with the placebo, in random order, with a 3-day washout period between the treatment periods. Clinical signs were assessed daily by the owner in all 31 dogs, using a subjective scoring scale. Twelve of the dogs were additionally evaluated at intervals by the investigators and similarly scored. Analysis of variance revealed no significant differences (P > 0.05) in owner or investigator scores assigned during placebo treatment, drug treatment, and no treatment periods. In an end-of-study evaluation, 24.1 per cent of owners reported satisfactory response to placebo capsules and 17.2 per cent reported satisfactory response to the drug, demonstrating a strong placebo effect. Short-duration treatment with WY-50295 did not appear to be effective in reducing clinical signs of atopy.

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

Background Women with breast cancer in sub-Saharan Africa are commonly diagnosed at advanced stages. In Tanzania, more than 80% of women are diagnosed with stage III or IV disease, and mortality rates are high. This study explored factors contributing to delayed diagnostic evaluation among women with breast cancer in Tanzania. Methods A qualitative study was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Twelve women with symptomatic pathologically proven breast cancer were recruited. In-depth, semi-structured interviews were conducted in Swahili. Interviews explored the women’s journey from symptom recognition to diagnosis, including the influence of breast cancer knowledge and pre-conceptions, health seeking behaviors, psychosocial factors, preference for alternative treatments, and the contribution of culture and norms. Audio-recorded interviews were transcribed and translated into English. Thematic analysis was facilitated by a cloud-based qualitative analysis software. Results All women reported that their first breast symptom was a self-identified lump or swelling. Major themes for factors contributing to delayed diagnostic presentation of breast cancer included lack of basic knowledge and awareness of breast cancer and misconceptions about the disease. Participants faced barriers with their local primary healthcare providers, including symptom mismanagement and delayed referrals for diagnostic evaluation. Other barriers included financial hardships, fear and stigma of cancer, and use of traditional medicine. The advice and influence of family members and friends played key roles in healthcare-seeking behaviors, serving as both facilitators and barriers. Conclusion Lack of basic knowledge and awareness of breast cancer, stigma, financial barriers, and local healthcare system barriers were common factors contributing to delayed diagnostic presentation of breast cancer. The influence of friends and family also played key roles as both facilitators and barriers. This information will inform the development of educational intervention strategies to address these barriers and improve earlier diagnosis of symptomatic breast cancer in Tanzania.

Using ground-based gravitational-wave detectors, we probe the mass function of intermediate-mass black holes (IMBHs) wherein we also include BHs in the upper mass gap $\sim 60-130~M_\odot$. Employing the projected sensitivity of the upcoming LIGO and Virgo fourth observing (O4) run, we perform Bayesian analysis on quasi-circular non-precessing, spinning IMBH binaries (IMBHBs) with total masses $50\mbox{--} 500\, M_\odot$, mass ratios 1.25, 4, and 10, and dimensionless spins up to 0.95, and estimate the precision with which the source-frame parameters can be measured. We find that, at $2\sigma$, the mass of the heavier component of IMBHBs can be constrained with an uncertainty of $\sim 10-40\%$ at a signal-to-noise ratio of $20$. Focusing on the stellar-mass gap with new tabulations of the $^{12}\text{C}(\alpha, \gamma)^{16} \text{O}$ reaction rate and its uncertanties, we evolve massive helium core stars using \MESA\, to establish the lower and upper edge of the mass gap as $\simeq$\,59$^{+34}_{-13}$\,$M_{\odot}$ and $\simeq$\,139$^{+30}_{-14}$\,$M_{\odot}$ respectively, where the error bars give the mass range that follows from the $\pm 3\sigma$ uncertainty in the $^{12}\text{C}(\alpha, \gamma) ^{16} \text{O}$ nuclear reaction rate. We find that high resolution of the tabulated reaction rate and fine temporal resolution are necessary to resolve the peak of the BH mass spectrum. We then study IMBHBs with components lying in the mass gap and show that the O4 run will be able to robustly identify most such systems. Finally, we re-analyse GW190521 with a state-of-the-art aligned-spin waveform model, finding that the primary mass lies in the mass gap with 90\% credibility., Comment: 29 pages, 18 figures

Allergen immunotherapy is currently the only causal treatment for allergic diseases in human beings and animals. It aims to re-direct the immune system into a tolerogenic or desensitized state. Requirements include clinical efficacy, safety, and schedules optimizing patient or owner compliance. To achieve these goals, specific allergens can be formulated with adjuvants that prolong tissue deposition and support uptake by antigen presenting cells, and/or provide a beneficial immunomodulatory action. Here, we depict adjuvant formulations being investigated for human and veterinary allergen immunotherapy.

PURPOSE Serious illness communication (SIC) in cancer care describes conversations between clinicians, patients, and families about prognosis and treatment decisions. Cultural context influences SIC. Researchers have studied SIC across diverse settings in Africa. We aimed to describe and synthesize the heterogeneous body of research on SIC practices, preferences, and needs in Africa to identify research and training priorities. METHODS Our search strategy identified studies that focused on SIC within cancer or palliative care in Africa. Following PRISMA guidelines, a systematic literature search was performed using PubMed, Embase, Web of Science, CINAHL, African Index Medicus, and PsycINFO, yielding 1811 unique titles. After sequential review of abstracts, full text, and cited references, 42 articles met inclusion criteria. Quantitative and qualitative data describing study characteristics, aims, methods, and findings were abstracted and analyzed using descriptive statistics and thematic analysis. Critical appraisal was performed using the Mixed Methods Appraisal Tool. RESULTS The 42 included articles were published from 1997-2021, half since 2017, representing 16 countries and all African Union regions: West (33%), East (29%), South (21%), North (12%), and Central (5%). Most study designs were qualitative (45%) or quantitative surveys (50%). Study participants included patients (35%), family caregivers (18%), doctors (18%), nurses (12%), and/or other (11%). Study aims focused on disclosure of diagnosis (27%) or prognosis (20%), breaking bad news (15%), general patient-clinician communication (12%), truth-telling (8%), shared decision-making (7%), information needs/preferences (5%), and/or advance care planning (5%). Despite diverse contexts, common themes emerged. Study authors frequently recommended communication skills training. Critical appraisal demonstrated high quality of studies overall. CONCLUSION Research on SIC in Africa has increased in recent years. Most studies have focused on information delivery by clinicians; fewer on eliciting information from patients (eg, shared decision-making, advanced care planning). Significant opportunities exist for further study and for communication skills training.

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy are sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results although promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimizing AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts will further improve compliance and efficacy of this proven treatment modality.

Rates of erosion over time provide a valuable tool for gauging tectonic and climatic drivers of landscape evolution. Here, we measure 10Be archived in quartz sediment from the Fish Creek-Vallecito basin to resolve a time-series of catchment averaged erosion rates and to test the hypothesis that aridity and increased climate variation after ca. 3 Ma led to an increase in erosion rates in this semi-arid, ice-free setting. The Fish Creek-Vallecito basin, located east of the Peninsular Ranges in southern California, is an ideal setting to derive a Plio-Pleistocene paleo-erosion rate record. The basin has a rapid sediment accumulation rate, a detailed magnetostratigraphic age record, and its stratigraphy has been exposed through recent, rapid uplift and erosion. A well-defined source region of uniform lithology and low erosion rate provides a high, reproducible 10Be signal. We find that paleo-erosion rates were remarkably consistent between 1 and 4 Ma, averaging 38 ± 24 m/Myr (2σ). Modern catchment averaged erosion rates are similar to the paleo-erosion rates. The uniformity of erosion over the past 4 Myr indicates the landscape was not significantly affected by late Pliocene global climate change, nor was it affected by a local long-term increase in aridity.

Green foxtail [Setaria viridis (L) Beauv.] and yellow foxtail [Setaria pumila (Poir.) Roem. & Schult.] are among the most abundant and troublesome annual grass weeds in cereal crops in the Northern Plains of the United States and the Prairie Provinces of Canada. Greenhouse and laboratory experiments were conducted to examine the differential responses of both weed species to foliar applications of the new triazolopyrimidine sulfonamide acetolactate synthase-inhibiting herbicide, pyroxsulam, and to determine the mechanism(s) of differential weed control. Foliar applications of pyroxsulam resulted in >90% control of yellow foxtail at rates between 7.5 and 15 g ai ha–1, whereas the same rates resulted in a reduced efficacy on green foxtail (≤81%). The absorption and translocation of [14C]pyroxsulam in green and yellow foxtail were similar and could not explain the differential whole-plant efficacy. Studies with [14C]pyroxsulam revealed a higher percentage of absorbed pyroxsulam was metabolized into an inacti...

Carbon and oxygen burning reactions, in particular, $^{12}$C+$^{12}$C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-$\gamma$ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for $^{12}$C+$^{12}$C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed., Comment: accepted for publication in Phys. Rev. Lett

The ^{12}C(α,γ)^{16}O reaction is one of the most crucial reactions in nuclear astrophysics. The E2 external capture to the ^{16}O ground state (GS) has not been emphasized in previous analyses but may make a significant contribution to the ^{12}C(α,γ)^{16}O cross section depending on the value of the GS asymptotic normalization coefficient (ANC). In the present work, we determine this ANC to be 337±45 fm^{-1/2} through the ^{12}C(^{11}B,^{7}Li)^{16}O reaction using a high-precision magnetic spectrograph. This sheds light on the existing large discrepancy of more than 2 orders of magnitude between the previously reported ANC values. Based on the new ANC, we experimentally constrain the GS external capture and show that through interference with the high energy tail of the 2^{+} subthreshold state, a substantial enhancement in the GS S_{E2}(300) factor can be obtained (70±7 keV b) compared to that of a recent review (45 keV b), resulting in an increase of the total S factor from 140 to 162 keV b, which is now in good agreement with the value obtained by reproducing supernova nucleosynthesis calculations with the solar-system abundances. This work emphasizes that the external capture contribution for the ground state transition cannot be neglected in future analyses of the ^{12}C(α,γ)^{16}O reaction.