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Purpose Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). Methods This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). Results Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). Conclusion There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Disruptions to developmental cell signaling pathways and transcriptional cascades have been implicated in tumor initiation, maintenance and progression. Resurgence of aberrant neurodevelopmental programs in the context of brain tumors highlights the numerous parallels that exist between developmental and oncologic mechanisms. A deeper understanding of how dysregulated developmental factors contribute to brain tumor oncogenesis and disease progression will help to identify potential therapeutic targets for these malignancies. In this review, we summarize the current literature concerning developmental signaling cascades and neurodevelopmentally-regulated transcriptional programs. We also examine their respective contributions towards tumor initiation, maintenance, and progression in both pediatric and adult brain tumors and highlight relevant differentiation therapies and putative candidates for prospective treatments.

We develop a complete local theory for CR embedded submanifolds of CR manifolds in a way which parallels the Ricci calculus for Riemannian submanifold theory. We define a normal tractor bundle in the ambient standard tractor bundle along the submanifold and show that the orthogonal complement of this bundle is not canonically isomorphic to the standard tractor bundle of the submanifold. By determining the subtle relationship between submanifold and ambient CR density bundles we are able to invariantly relate these two tractor bundles, and hence to invariantly relate the normal Cartan connections of the submanifold and ambient manifold by a tractor analogue of the Gauss formula. This leads also to CR analogues of the Gauss, Codazzi, and Ricci equations. The tractor Gauss formula includes two basic invariants of a CR embedding which, along with the submanifold and ambient curvatures, capture the jet data of the structure of a CR embedding. These objects therefore form the basic building blocks for the construction of local invariants of the embedding. From this basis we develop a broad calculus for the construction of the invariants and invariant differential operators of CR embedded submanifolds. The CR invariant tractor calculus of CR embeddings is developed concretely in terms of the Tanaka-Webster calculus of an arbitrary (suitably adapted) ambient contact form. This enables straightforward and explicit calculation of the pseudohermitian invariants of the embedding which are also CR invariant. These are extremely difficult to find and compute by more naïve methods. We conclude by establishing a CR analogue of the classical Bonnet theorem in Riemannian submanifold theory.

Background Cancer treatment requires substantial demands on patients and their caregivers. Mobile apps can provide support for self‐management during oncology treatment, but few have been rigorously evaluated. Methods A 3‐month randomized controlled trial was conducted at a large cancer center to evaluate the efficacy of an app (LivingWith®) that provides self‐management support during cancer treatment on quality of life and health care utilization. Patients in chemotherapy treatment were randomized into the intervention (n = 113) and control group (n = 111). Intervention group participants agreed to use the app weekly for 3 months, and all participants completed a survey at enrollment and after 3 months to evaluate changes in quality of life and health care utilization. Results Retention rate was 75.4% with 169 participants completing the follow‐up survey. The intervention group reported 0.74 fewer medical office visits (p = 0.043) and 0.24 fewer visits with a mental health professional (p = 0.061) during the 3 and month intervention compared with controls. There were no significant changes by study group in quality of life, or emergency room and urgent care visits. Among intervention participants, 75.3% reported using the app and on average, used it 11.7 times during the 3‐month intervention. Reasons for not using the app among intervention participants included lack of time, lack of interest in apps, and usability challenges. Conclusions and Relevance Apps are inexpensive and scalable tools that can provide additional support for individuals coping with complex cancer treatments. This trial provides evidence that a well‐designed oncology support app used during chemotherapy resulted in fewer clinic visits. Still, nearly a quarter of participants randomized to the intervention arm reported never using the app due to personal preference and usability challenges, which points to future opportunities for calibrating target user population and improving user‐centered design. Clinicaltrials.gov identifier: NCT04331678. This randomized controlled trial of oncology patients provides evidence that a well‐designed oncology support mobile app used during chemotherapy resulted in fewer clinic visits.

This paper discusses how smallholder settlers on government-sponsored oil palm land settlement schemes in West New Britain Province, Papua New Guinea, have responded to rising land pressures since the late 1960s when the settlement schemes were established. After providing an overview of the oil palm industry in Papua New Guinea and key smallholder groups, the paper focuses on how settlers responded to land and income pressures through technical, social and institutional innovations. It is argued that while smallholders have experienced significant constraints and threats to their livelihoods, most have been able to exercise a fair degree of agency to improve their livelihoods. Institutional factors have also been critical to enhancing smallholders’ adaptive capacity in responding to rising land and economic pressures. Cet article examine les moyens par lesquels les petits exploitants agricoles installés sur les plantations de palmiers à huile soutenues par le gouvernement dans la province de West New Britain, en Papouasie-Nouvelle-Guinée, ont réagi aux pressions foncières croissantes depuis la fin des années 1960, date à laquelle les programmes de colonisation ont été mis en place. Après avoir présenté un aperçu de l’industrie du palmier à huile en Papouasie-Nouvelle-Guinée et les principaux groupes de petits exploitants, l’article se concentre sur la manière dont les colons ont répondu aux pressions foncières et démographiques par le biais d’innovations techniques, sociales et institutionnelles. Il montre que, si les petits exploitants ont subi des contraintes menaçant fortement leurs moyens de subsistance, la plupart ont pu exercer un certain degré d’autonomie pour les améliorer. Les facteurs institutionnels ont également été essentiels pour renforcer la capacité d’adaptation des petits exploitants à répondre aux pressions foncières et économiques croissantes.

Background Women undergoing treatment for breast cancer require frequent clinic visits for maintenance of therapy. With COVID-19 causing health care disruptions, it is important to learn about how this population’s access to health care has changed. This study compares self-reported health care utilization and changes in factors related to health care access among women treated at a cancer center in the mid-South US before and during the pandemic. Methods Participants ( N  = 306) part of a longitudinal study to improve adjuvant endocrine therapy (AET) adherence completed pre-intervention baseline surveys about their health care utilization prior to AET initiation. Questions about the impact of COVID-19 were added after the pandemic started assessing financial loss and factors related to care. Participants were categorized into three time periods based on the survey completion date: (1) pre-COVID (December 2018 to March 2020), (2) early COVID (April 2020 – December 2020), and later COVID (January 2021 to June 2021). Negative binomial regression analyses used to compare health care utilization at different phases of the pandemic controlling for patient characteristics. Results Adjusted analyses indicated office visits declined from pre-COVID, with an adjusted average of 17.7 visits, to 12.1 visits during the early COVID period ( p  = 0.01) and 9.9 visits during the later COVID period ( p  < 0.01). Hospitalizations declined from an adjusted average 0.45 admissions during early COVID to 0.21 during later COVID, after vaccines became available ( p  = 0.05). Among COVID period participants, the proportion reporting changes/gaps in health insurance coverage increased from 9.5% participants during early-COVID to 14.8% in the later-COVID period (p = 0.05). The proportion reporting financial loss due to the pandemic was similar during both COVID periods (34.3% early- and 37.7% later-COVID, p = 0.72). The proportion of participants reporting delaying care or refilling prescriptions decreased from 15.2% in early-COVID to 4.9% in the later-COVID period (p = 0.04). Conclusion COVID-19 caused disruptions to routine health care for women with breast cancer. Patients reported having fewer office visits at the start of the pandemic that continued to decrease even after vaccines were available. Fewer patients reported delaying in-person care as the pandemic progressed.

Background: Patients performing self-triage for chest pain need to pick an algorithm which includes questions pertinent to chest pain to triage accurately. Objective: Our study reviews patient self-triage choices and outcomes for patients who completed an online self-triage encounter before being triaged by a nurse for chest pain. Methods: Patients who underwent telephone nurse triage for chest pain, and also had an online self-triage encounter within the prior 24 hours were reviewed for the frequency with which they chose “chest pain” as their symptom to triage for during self-triage, whether they reported chest pain during the self-triage encounter (if asked as part of the algorithm for their chosen self-triage symptom) and whether the patient had any follow up evaluation within 1 week. Results: There were 70 self-triage and nurse triage dyads during the study period where triage nurses chose “chest pain” as the primary symptom to be triaged for during the telephone triage encounter. Of these, only 5 (7.1%) patients chose the “chest pain” self-triage option during online self-triage. During the self-triage encounter, 50 (71%) reported chest pain, 10 (14%) denied chest pain and 10 chose to self-triage their symptoms with an algorithm that did not include a question on whether chest pain was present. Of the 70 total dyads 59 (84%) had a follow up emergency department (40 patients) or office visit (19 patients) documented. Conclusion: Most patients chosen to be triaged for chest pain by triage nurses did not choose the online self-triage algorithm for chest pain even though the majority did report chest pain during their self-triage encounter (when asked). This is concerning from a safety perspective as a non-chest pain self-triage option chosen by the patient may not always ask about the presence or absence of chest pain and thus could increase the risk of being triaged inaccurately. Implications for improvement of self-triage could include diagrams for patients to choose the symptom area.

Although a reliable method for detection of cancer cells in blood would be an important tool for diagnosis and monitoring of solid tumors in early stages, current technologies cannot reliably detect the extremely low concentrations of these rare cells. The preferred method of detection, automated digital microscopy (ADM), is too slow to scan the large substrate areas. Here we report an approach that uses fiber-optic array scanning technology (FAST), which applies laser-printing techniques to the rare-cell detection problem. With FAST cytometry, laser-printing optics are used to excite 300,000 cells per sec, and emission is collected in an extremely wide field of view, enabling a 500-fold speed-up over ADM with comparable sensitivity and superior specificity. The combination of FAST enrichment and ADM imaging has the performance required for reliable detection of early-stage cancer in blood.

deformations of the CR structure of a compact strictly pseudoconvex hypersurface M in C 2 are encoded by complex functions on M . In sharp contrast with the higher dimensional case, the natural integrability condition for 3-dimensional CR structures is vacuous, and generic deformations of a compact strictly pseudoconvex hypersurface M ⊆ C 2 are not embeddable even in C N for any N . A fundamental (and difficult) problem is to characterize when a complex function on M ⊆ C 2 gives rise to an actual deformation of M inside C 2 . In this paper we study the embeddability of families of deformations of a given embedded CR 3-manifold, and the structure of the space of embeddable CR structures on S 3 . We show that the space of embeddable deformations of the standard CR 3-sphere is a Frechet submanifold of C ∞ ( S 3 , C ) near the origin. We establish a modified version of the Cheng–Lee slice theorem in which we are able to characterize precisely the embeddable deformations in the slice (in terms of spherical harmonics). We also introduce a canonical family of embeddable deformations and corresponding embeddings starting with any infinitesimally embeddable deformation of the unit sphere in C 2 .

Introduction/Background*Malawi ranks as the country with the second highest CC incidence (72.9/100 000) and mortality (54.5/100 000).The facilities face serious challenges as the country has no functioning radiotherapy center, which leaves patients with Locally Advance Cervical Cancer (LACC) without curative options. We adopted NACT as a down-staging strategy for patients with LACC, to provide them curative options.The aim of the survey was to assess whether NACT is an effective strategy in being able to provide adequate surgery for stage IB3, IIA2, and IIB patients.MethodologyCohort analysis of data from women (>=18 y.o.) receiving a Radical Hysterectomy (RH) in MSF Malawian cancer program between December 2019 and March 2021.Initial and post-pathology FIGO staging were described and compared according to individual characteristics and therapy received.Comparisons of proportions were performed using the appropriate statistical test.All analyses were performed using Stata16 (Stata Corp).Data was extracted from Redcap Malawi and a Microsoft Excel database.Data analyses were performed using Excel and Stata 16 (version 16.1).Result(s)*Between December 1, 2019 and March 30, 2021, 97 women undergo RH at MSF Cervical Cancer project at Queen Elizabeth Central Hospital (QECH).Out of these patients, 47 received NACT.Among those patients, we observe a change in FIGO stage for 46 (p -value <0.005).NACT improved post-pathology FIGO stage for 42 patients (p-value<0.005): 17 patients had complete pathological response, and 25 presented with partial response.Four patients clinically worsened FIGO stage, requiring chemo radiation as treatment.There was a significant decrease in histopathology results for parametrium, LVSI, LN involvement, and margin involvement (p-value<0.005).According to Clavien-Dindo Classification 12 patients had post operative complications: 5 Grade I, 1 Grade II, 4 Grade III a, and 2 Grade III b. Two patients died after NACT and RH died (4.3%).Patients that received NACT in the MSF cohort had 17.3% less complications than non-NACT patients.Conclusion*In the absence of radiation therapy option, NACT seems to be an effective strategy in improving patient FIGO stage enough for adequate surgery.Long term follow up is required to assess its impact on disease free survival.