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When fabricating magnetic components for micro-electro-mechanical systems, the intrinsic material properties as well as the magnetic anisotropy of the deposited material and the fabricated devices must be adjusted to the application. This work focuses on electrochemically deposited cobalt phosphorus layers from a sulfate-based electrolyte to be used as hard magnetic scales in position measurement systems. In preliminary tests round discs (5 mm diameter, 20 or 10 μm height) were fabricated, showing the influence of three process parameters (current density, pH-value and temperature) on the chemical composition and the magnetic behavior of the deposited cobalt phosphorus. Hereby deposition parameters to produce hard magnetic cobalt phosphorus are defined. Deposits with up to 6 wt.-% phosphorus show hard magnetic behavior, whereas deposits with more than 6 wt.-% show soft magnetic behavior. This is correlated with a transition from crystalline to amorphous structures. In further investigations arrays of micro scales (40 μm width, 10 μm height) were fabricated to show the influence of direct current and pulsed current on the properties of the deposits. Pulsed current increases coercive field strength by about 40 %, resulting in maximum values of 23 kA/m (in-plane) and 14 kA/m (out-of-plane). Remanence increases by about 30 %, resulting in maximum values of 0.40 T (in-plane) and 0.2 T (out-of-plane). Pulse plating changes preferred orientation from (110) to (100) and slightly increases grain size by about 20 %, resulting in an average grain size of 25 nm.

Medial patellofemoral ligament (MPFL) reconstruction with allograft is the current standard surgical treatment for recurrent lateral patellar instability. The authors describe a technique for MPFL repair that is augmented with a reinforced bioinductive implant inserted using a double-bundle patella docking technique. The tensile strength of the implant provides resistance to patellar translation during healing, offering a notable advantage to historically described MPFL repair techniques and paralleling the benefits of allograft over autograft when used for MPFL reconstruction.

Objective: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD). Methods: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201–400 mg/day (n = 51, 48.5%) and 401–650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring. Results: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups. Conclusion: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

Research indicates multiple causes of declining total fertility rate (TFR) in developing countries, including reduced child mortality, improved education and economy, family planning programmes and female empowerment. However, public opinions about the causes have rarely been studied. Using surveys in 2022 in Sweden and Nigeria, we compare answers of educated citizens to the question of why fertility (birth rate) has fallen in developing countries (also in Nigeria). In Sweden, 72 per cent of respondents suggested improved living conditions, including economy and education, lower infant mortality and generally progressive development. In contrast, in Nigeria 66 per cent of the respondents suggested that poverty, bad socioeconomic conditions and poor health cause declining birth rates. Birth rates were thus assumed to be falling mainly because the conditions in Nigeria are generally getting worse, not better. A contributing reason for the difference of opinions between the countries may be social norms for large families in Nigeria. Few Swedish respondents suggested family planning (1.9% of answers) but this answer was more common in Nigeria (5.9%). In Sweden, women answered contraceptive use (17%) more often than did men (4.5%), while in Nigeria the contraception answer hardly differed between men (6.1%) and women (5.7%). Only minor differences in opinion existed between the southern and northern (Muslim-dominated) states in Nigeria, among educated respondents that participated in this survey. We recommend more, and extended surveys.

Spontaneous uterine rupture in unscarred uteri complicated by pulmonary emboli is a rare event with major maternal morbidity and mortality.This is a case of a 32-year-old woman, G1P0, at term, with no pertinent past medical/surgical history, who underwent an emergency cesarean delivery for failed induction of labor complicated by uterine rupture. Post-operatively, the patient was tachycardic and hypoxic. CT arteriogram revealed massive bilateral pulmonary emboli, and she was transferred for specialist care. An emergency pulmonary embolectomy and implantation of an extracorporeal right ventricular assist device were performed. Once the patient was clinically stable, an evaluation for thrombophilias and collagen disorders was done, and was positive for a variant of unknown significance in the ELN gene (c.205G > C).This case report highlights a potential connection between uterine ruptures, hemorrhage, and multiple, large pulmonary emboli. The authors propose a multidisciplinary discussion and evaluation to identify risk factors and biologic causes for these rare but life-threatening complications.

Abstract Background This study presents an intervention designed to foster the implementation of health promotion programs within District Municipality Community Centers (DMCCs) in Jerusalem, and the creation of a peer network of healthy settings with a shared aspiration of collaborating and implementing health-promoting policies at the community level. We also present the evaluation strategy, based on the EQUIHP and RE-AIM frameworks. Methods Twenty DMCCs completed our program. This evaluation research involved a comprehensive seminar during the first year for DMCCs coordinators, teaching them the principles of health promotion. An educational kit was distributed during the second year. The evaluation strategy included a process evaluation and annual evaluations based on the EQUIHP and RE-AIM frameworks. The EQUIHP tool was divided into four dimensions of evaluation: 1) Framework of health promotion principles, 2) Project development and implementation, 3) Project management, and 4) Sustainability; while the RE-AIM domains included: 1)Reach, 2)Effectiveness, 3)Adoption, 4)Implementation and 5)Maintenance. Results The program led to high responsiveness among DMCCs and to the implementation of diverse health promotion initiatives, with a participation of approximately 29,191 residents. The EQUIHP evaluation showed an improvement in program quality in Year 2. The final RE-AIM evaluation presented a total median score of 0.61 for all domains, where 0 was non-performance and 1.0 was full performance. The ‘Framework of health promotion principles’ and ‘Reach’ components received the highest median score (0.83, 1.0 and 0.87), while the ‘Sustainability and ‘Maintenance’ components received the lowest (0.5). Conclusions This innovative program adapts the Healthy Cities approach (initiated by the World Health Organization in 1986) to the development of community center health-promoting settings within the larger municipal framework, training local community center staff members to assess and address local health concerns and build community capacity. The local focus and efforts may help community actors to create health promotion programs more likely to be adopted, feasible in the ‘real-world’ and able to produce public health impact in the communities where people live. Moreover, collaboration and cooperation among DMCCs may lead to a broader community health vision, forging coalitions that can advocate more powerfully for health promotion. Trial registration NIH trial registration number: NCT04470960. Retrospectively registered on: 14/07/2020.

Background: Antenatal care provides unique opportunities to assess severe acute respiratory syndrome coronavirus 2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. We estimated seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid immunoglobulin G) among pregnant people, and evaluated transplacental transfer efficiency. Objective and design: We conducted a cross-sectional study to measure severe acute respiratory syndrome coronavirus 2 seroprevalence, and a prospective cohort study to longitudinally measure anti-nucleocapsid immunoglobulin G responses and transplacental transfer of maternally derived anti-nucleocapsid antibodies. Methods: We screened pregnant people for the seroprevalence study between 9 December 2020 and 19 June 2021 for anti-nucleocapsid immunoglobulin G in Seattle, Washington. We enrolled anti-nucleocapsid immunoglobulin G positive people from the seroprevalence study or identified through medical records with positive reverse transcription polymerase chain reaction or antigen positive results in a prospective cohort between 9 December 2020 and 9 August 2022. Results: In the cross-sectional study (N = 1284), 5% (N = 65) tested severe acute respiratory syndrome coronavirus 2 anti-nucleocapsid immunoglobulin G positive, including 39 (60%) without prior positive reverse transcription polymerase chain reaction results and 42 (65%) without symptoms. In the prospective cohort study (N = 107 total; N = 65 from the seroprevalence study), 86 (N = 80%) had anti-nucleocapsid immunoglobulin G positive results during pregnancy. Among 63 participants with delivery samples and prior anti-nucleocapsid positive results, 29 (46%) were anti-nucleocapsid immunoglobulin G negative by delivery. Of 34 remaining anti-nucleocapsid immunoglobulin G positive at delivery with paired cord blood, 19 (56%) had efficient transplacental anti-nucleocapsid immunoglobulin G antibody transfer. Median time from first anti-nucleocapsid immunoglobulin G positive to below positive antibody threshold was 19 weeks and did not differ by prior positive reverse transcription polymerase chain reaction status. Conclusions: Maternally derived severe acute respiratory syndrome coronavirus 2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants.

Subsequent recall is improved if students try to recall target material during study (self-testing) versus simply re-reading it. This effect is consistent with the notion of "desirable difficulties." If the learning experience involves difficulties that induce extra effort, then retention may be improved. Not all difficulties are desirable, however. Difficult-to-read ("disfluent") typefaces yield inconsistent results. A new disfluent font, Sans Forgetica, was developed and alleged to promote deeper processing and improve learning. Although it would be invaluable if changing the font could enhance learning, the few studies on Sans Forgetica have been inconsistent, and focused on short retention intervals (0-5 minutes). We investigated a 1-week interval to increase practical relevance and because some benefits only manifest after a delay. A testing-effect manipulation was also included. Students (N = 120) learned two passages via different methods (study then re-study vs. study then self-test). Half the students saw the passages in Times New Roman and half in Sans Forgetica. Recall test scores were higher for passages learned via self-testing than restudying, but the effect of font and the interaction were nonsignificant. We suggest that disfluency increases the local (orthographic) processing effort on each word but slowed reading might impair relational processing across words. In contrast, testing and generation effect manipulations often engage relational processing (question: answer; cue: target)--yielding subsequent benefits on cued-recall tests. We elaborate this suggestion to reconcile conflicting results across studies.

Abstract In 2020, 77% of malaria cases in the Americas were concentrated in Venezuela, Brazil, and Colombia. These countries are characterized by a heterogeneous malaria landscape and malaria hotspots. Furthermore, the political unrest in Venezuela has led to significant cross-border population movement. Hence, the aim of this study was to describe spatial patterns and identify significant climatic drivers of malaria transmission along the Venezuela-Brazil-Guyana border, focusing on Bolivar state, Venezuela and Roraima state, Brazil. Malaria case data, stratified by species from 2016 to 2018, were obtained from the Brazilian Malaria Epidemiology Surveillance Information System, the Guyana Vector Borne Diseases Program, the Venezuelan Ministry of Health, and civil society organizations. Spatial autocorrelation in malaria incidence was explored using Getis-Ord (Gi*) statistics. A Poisson regression model was developed with a conditional autoregressive prior structure and posterior parameters were estimated using the Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. There were 685,498 malaria cases during the study period. Plasmodium vivax was the predominant species (71.7%, 490,861). Malaria hotspots were located in eight municipalities along the Venezuela and Guyana international borders with Brazil. Plasmodium falciparum increased by 2.6% (95% credible interval [CrI] 2.1%, 2.8%) for one meter increase in altitude, decreased by 1.6% (95% CrI 1.5%, 2.3%) and 0.9% (95% CrI 0.7%, 2.4%) per 1 cm increase in 6-month lagged precipitation and each 1 °C increase of minimum temperature without lag. Each 1 °C increase of 1-month lagged maximum temperature increased P. falciparum by 0.6% (95% CrI 0.4%, 1.9%). P. vivax cases increased by 1.5% (95% CrI 1.3%, 1.6%) for one meter increase in altitude and decreased by 1.1% (95% CrI 1.0%, 1.2%) and 7.3% (95% CrI 6.7%, 9.7%) for each 1 cm increase of precipitation lagged at 6-months and 1 °C increase in minimum temperature lagged at 6-months. Each 1°C increase of two-month lagged maximum temperature increased P. vivax by 1.5% (95% CrI 0.6%, 7.1%). There was no significant residual spatial clustering after accounting for climatic covariates. Malaria hotspots were located along the Venezuela and Guyana international border with Roraima state, Brazil. In addition to population movement, climatic variables were important drivers of malaria transmission in these areas.

Abstract Background Roraima state is the northernmost state in Brazil and the primary border-crossing point between Brazil and Venezuela. The uncontrolled surge of malaria in Venezuela, coupled with mass migration of Venezuelans to neighbouring countries and the upward trend in informal mining in the state, pose a serious threat to the broader region, especially to migrant, indigenous and mining populations, jeopardizing malaria elimination efforts. This study describes changes in the epidemiological profile of malaria in Roraima state related to time, place and populations at risk from 2016 to 2020. Methods De-identified malaria surveillance data were obtained from the Malaria Epidemiological Surveillance System from 2016 to 2020. Pearson’s chi-square tested differences between imported and autochthonous cases. Multivariable logistic regression was used to identify risk factors for imported versus autochthonous cases by demographic characteristics. Results Odds of being an imported case were higher for Plasmodium falciparum cases (AOR = 2.08). However, as the number of cases from Venezuela decreased in 2020 following closure of the border, the proportion of P. falciparum cases increased markedly, from 6.24% in 2019 to 18.50% in 2020. Over the 5-year period, the odds of being an imported case among miners were about nine times higher than the general population (AOR = 8.99). The proportion of total malaria cases that were among indigenous people increased from 33.09% in 2016 to 54.83% in 2020. Indigenous children had a higher burden of malaria with over 40% of cases in children 0 to 9 years old, compared to 8% in non-indigenous children 0 to 9 years old. In some municipalities, place of infection differed from place of notification, with a large proportion of cases in these municipalities reporting in Boa Vista. Conclusions Malaria remains a serious threat in Roraima state, especially among high-risk populations, such as miners, migrants, and indigenous people. As malaria cases have increased among indigenous people and miners, and the proportion of P. falciparum cases has increased, elimination efforts require understanding of these risk factors to tailor interventions appropriately. Furthermore, cross-border surveillance systems need to be urgently strengthened at formal and unofficial border points, especially since the border with Venezuela reopened in July 2021.

Abstract Globally, cross-border importation of malaria has become a challenge to malaria elimination. The border areas between Brazil and Venezuela have experienced high numbers of imported cases due to increased population movement and migration out of Venezuela. This study aimed to identify risk factors for imported malaria and delineate imported malaria hotspots in Roraima, Brazil and Bolivar, Venezuela between 2016 and 2018. Data on malaria surveillance cases from Roraima, Brazil and Bolivar, Venezuela from 2016 to 2018 were obtained from national surveillance systems: the Brazilian Malaria Epidemiology Surveillance Information System (SIVEP-Malaria), the Venezuelan Ministry of Health and other non-government organizations. A multivariable logistic regression model was used to identify the risk factors for imported malaria. Spatial autocorrelation in malaria incidence was explored using Getis-Ord (Gi*) statistics. During the study period, there were 11,270 (24.3%) and 4072 (0.7%) imported malaria cases in Roraima, Brazil and Bolivar, Venezuela, respectively. In the multivariable logistic regression for Roraima, men were 28% less likely to be an imported case compared to women (Adjusted Odds Ratio [AOR] = 0.72; 95% confidence interval [CI] 0.665, 0.781). Ages 20–29 and 30–39 were 90% (AOR = 1.90; 95% CI 1.649, 2.181) and 54% (AOR = 1.54; 95% CI 1.331, 1.782) more likely to be an imported case compared to the 0–9 year age group, respectively. Imported cases were 197 times (AOR = 197.03; 95% CI 175.094, 221.712) more likely to occur in miners than those working in agriculture and domestic work. In Bolivar, cases aged 10–19 (AOR = 1.75; 95% CI 1.389, 2.192), 20–29 (AOR = 2.48; 95% CI 1.957, 3.144), and 30–39 (AOR = 2.29; 95% CI 1.803, 2.913) were at higher risk of being an imported case than those in the 0–9 year old group, with older age groups having a slightly higher risk compared to Roraima. Compared to agriculture and domestic workers, tourism, timber and fishing workers (AOR = 6.38; 95% CI 4.393, 9.254) and miners (AOR = 7.03; 95% CI 4.903, 10.092) were between six and seven times more likely to be an imported case. Spatial analysis showed the risk was higher along the international border in the municipalities of Roraima, Brazil. To achieve malaria elimination, cross-border populations in the hotspot municipalities will need targeted intervention strategies tailored to occupation, age and mobility status. Furthermore, all stakeholders, including implementers, policymakers, and donors, should support and explore the introduction of novel approaches to address these hard-to-reach populations with the most cost-effective interventions.

We explored online dissertation chairs' perceptions of trust in the mentor-mentee relationship, as trust was identified as a crucial factor in the success of doctoral students. Through the implementation of a multiple-case study, and a qualitative, online questionnaire, and through qualitative data analysis, we discovered 16 chairs' perceptions of trust and that student vulnerability is an important part of the relationship that chairs consistently work to alleviate. Findings point to the importance for chairs to establish trust through feedback, consistency, and personal connections with students. Second, chairs perceived student vulnerability to include both students' discussion of their academic skills (or lack thereof) and their willingness to share personal information. Chairs were very resourceful in enacting strategies to alleviate all types of student vulnerability, including recognizing student strengths and pointing to the positives of vulnerability and by offering scholarly resources for students to develop their academic strengths.

Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine. Approaches being explored include subunit vaccines and outer membrane vesicles (OMVs), but an ideal candidate remains elusive. Meningococcal OMV-based vaccines have been associated with reduced rates of gonorrhea in retrospective epidemiologic studies, and with accelerated gonococcal clearance in mouse vaginal colonization models. Cross-protection is attributed to shared antigens and possibly cross-reactive, bactericidal antibodies. Using a Candidate Antigen Selection Strategy (CASS) based on the gonococcal transcriptome during human mucosal infection, we identified new potential vaccine targets that, when used to immunize mice, induced the production of antibodies with bactericidal activity against N. gonorrhoeae strains. The current study determined antigen recognition by human sera from N. gonorrhoeae-infected subjects, evaluated their potential as a multi-antigen (combination) vaccine in mice and examined the impact of different adjuvants (Alum or Alum+MPLA) on functional antibody responses to N. gonorrhoeae. Our results indicated that a stronger Th1 immune response component induced by Alum+MPLA led to antibodies with improved bactericidal activity. In conclusion, a combination of CASS-derived antigens may be promising for developing effective gonococcal vaccines.

Fault slip during plate boundary earthquakes releases a portion of the shear stress accumulated due to frictional resistance to relative plate motions. Investigation of 101 large [moment magnitude (Mw) ≥ 7] subduction zone plate boundary mainshocks with consistently determined coseismic slip distributions establishes that 15 to 55% of all master event-relocated aftershocks with Mw ≥ 5.2 are located within the slip regions of the mainshock ruptures and few are located in peak slip regions, allowing for uncertainty in the slip models. For the preferred models, cumulative deficiency of aftershocks within the central three-quarters of the scaled slip regions ranges from 15 to 45%, increasing with the total number of observed aftershocks. The spatial gradients of the mainshock coseismic slip concentrate residual shear stress near the slip zone margins and increase stress outside the slip zone, driving both interplate and intraplate aftershock occurrence near the periphery of the mainshock slip. The shear stress reduction in large-slip regions during the mainshock is generally sufficient to preclude further significant rupture during the aftershock sequence, consistent with large-slip areas relocking and not rupturing again for a substantial time.

Abstract Background School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of World Vision Asia Pacific Region’s COVID-19 response-assessments in May–June 2020, this study examined whether adolescents’ study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender. Methods The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10–18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19. Results Participation in remote education was low (range: 0.5–20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36–0.55 (n = 5 countries) or play video games with a range of AOR: 0.55–0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45). Conclusions An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents’ psychosocial status is at higher risk when facing the challenges of this pandemic.

The frequency-magnitude distribution follows the Gutenberg-Richter empirical law, in which the scaling between small and large earthquakes is represented by the b-value. Laboratory experiments have shown that the b-value is related to fault mechanics with an inverse dependency to the differential stress, as was also inferred from observational datasets through relations with earthquake depth and style of faulting. In this study, we aim to obtain a better understanding of the geological structure and tectonics along the Dead Sea transform (DST), by examining relations of the b-value to three source parameters: the earthquake depth, the seismic moment release, and the predominant style of faulting. We analyse a regional earthquake catalogue of ∼20,300 earthquakes that were recorded between 1983 and 2020 in a regional rectangle between latitudes 27.5°N−35.5°N and longitudes 32°E−38°E. We convert the duration magnitudes, Md, to moment magnitudes, Mw, applying a new regional empirical relation, by that achieving a consistent magnitude type for the entire catalogue. Exploring the variations in the b-value for several regions along and near the DST, we find that the b-value increases from 0.93 to 1.19 as the dominant style of faulting changes from almost pure strike-slip, along the DST, to normal faulting at the Galilee, northern Israel. Focusing on the DST, our temporal analysis shows an inverse correlation between the b-value and the seismic moment release, whereas the spatial variations are more complex, showing combined dependencies on seismogenic depth and seismic moment release. We also identify seismic gaps that might be related to locking or creeping of sections along the DST and should be considered for hazard assessment. Furthermore, we observe a northward decreasing trend of the b-value along the DST, which we associate to an increase of the differential stress due to structural variations, from more extensional deformation in the south to more compressional deformation in the north.

Nano-computed tomography (nano-CT) based on scanning electron microscopy (SEM) is utilized for multimodal material characterization in one instrument. Since SEM-based CT uses geometrical magnification, X-ray targets can be adapted without any further changes to the system. This allows for designing targets with varying geometry and chemical composition to influence the X-ray focal spot, intensity and energy distribution with the aim to enhance the image quality. In this paper, three different target geometries with a varying volume are presented: bulk, foil and needle target. Based on the analyzed electron beam properties and X-ray beam path, the influence of the different target designs on X-ray imaging is investigated. With the obtained information, three targets for different applications are recommended. A platinum (Pt) bulk target tilted by 25° as an optimal combination of high photon flux and spatial resolution is used for fast CT scans and the investigation of high-absorbing or large sample volumes. To image low-absorbing materials, e.g., polymers or organic materials, a target material with a characteristic line energy right above the detector energy threshold is recommended. In the case of the observed system, we used a 30° tilted chromium (Cr) target, leading to a higher image contrast. To reach a maximum spatial resolution of about 100 nm, we recommend a tungsten (W) needle target with a tip diameter of about 100 nm.

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P

Recent studies have identified oncogenic lesions in Philadelphia chromosome-positive (Ph+)  acute lymphoblastic leukemia (ALL) and ABL1 kinase mutations that confer resistance to tyrosine kinase inhibitors. We sought to determine the prevalence and clinical impact of these lesions in patients on CALGB 10001, a previously reported Phase II study of imatinib, chemotherapy, and hematopoietic cell transplant in adult Ph + ALL. Of the 58 enrolled, 22 relapsed. By direct sequencing, an ABL1 kinase mutation known to induce imatinib resistance was present at relapse in 13 of 20. Using quantitative PCR assays, the mutations were detectable at diagnosis or early during treatment in most (62%) relapsed patients. Aberrations in IKZF1, CDKN2A/B, and PAX5 were assessed in 28 samples using SNP arrays and genomic DNA sequencing. Of these, 22 (79%) had IKZF1 deletion. The combination of IKZF1 deletion and p210 BCR-ABL1 (p

Abstract Background BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. Methods A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. Results Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. Conclusions The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.

SARS-CoV-2 was identified as the pathogenic agent causing the COVID-19 pandemic. Among the proteins codified by this virus, the Spike protein is one of the most-external and -exposed. A fragment of the Spike protein, named the receptor binding domain (RBD), interacts with the ACE2 receptors of human cells, allowing the entrance of the viruses. RBD has been proposed as an interesting protein for the development of diagnosis tools, treatment, and prevention of the disease. In this work, a method for recombinant RBD production using Pichia pastoris as a cell factory in a stirred-tank bioreactor (SRTB) up to 7 L was developed. Using a basal saline medium with glycerol, methanol, and compressed air in a four-stage procedure, around 500 mg/L of the raw RBD produced by yeasts (yRBD) and 206 mg/L of purified (>95%) RBD were obtained. Thereby, the proposed method represents a feasible, simple, scalable, and inexpensive procedure for the obtention of RBD for diagnosis kits and vaccines’ formulation.

Malaria was the leading cause of post-neonatal deaths in Mozambique in 2017. The use of insecticide treated nets (ITNs) is recognized as one of the most effective ways to reduce malaria mortality in children. No previous analyses have estimated changes in mortality attributable to the scale-up of ITNs, accounting for provincial differences in mortality rates and coverage of health interventions. Based upon annual provincial ownership coverage of ITNs, the Lives Saved Tool (LiST), a multi-cause mathematical model, estimated under-5 lives saved attributable to increased household ITN coverage in 10 provinces of Mozambique between 2012 and 2018, and projected lives saved from 2019 to 2025 if 2018 coverage levels are sustained. An estimated 14,040 under-5 child deaths were averted between 2012 and 2018. If 2018 coverage levels are maintained until 2025, an additional 33,277 child deaths could be avoided. If coverage reaches at least 85% in all ten provinces by 2022, then a projected 36,063 child lives can be saved. From 2012 to 2018, the estimated number of lives saved was highest in Zambezia and Tete provinces. Increases in ITN coverage can save a substantial number of child lives in Mozambique. Without continued investment, thousands of avoidable child deaths will occur.

The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article.

In April 2020, Vietnam initiated a country-wide lockdown to curb the spread of COVID-19. This secondary data analysis evaluates whether NGO-supported households (n = 3,431) reporting to be severely impacted by the lockdowns differ from those reporting a lesser impact, regarding food availability within households and at markets and affordability. 19.2% of respondents indicated that the pandemic had severely impacted their livelihoods. In the severely impacted group, there was a higher percentage of urban residents (25.3 vs. 8.6%; p < 0.001), households reporting decreased income (85.4 vs. 39.9%), and females (56.4 vs. 45.6%; p < 0.001) than in the less impacted group. Both groups reported similar availabilities of staple food groups at the household-level, but the availability of green vegetables was lower in the severely affected group (Adjusted OR [aOR] = 0.62, 95% CI: 0.38, 1.00) than in the less affected group. However, local market availability of hygiene items (aOR = 1.64, 95% CI: 1.13, 2.39) and essential medicines (aOR = 1.80, 95% CI: 1.29, 2.50) were higher for the more impacted group relative to the less impacted group. While the self-reported livelihood impact of COVID-19 was associated with a loss of income, the association of indicators of food availability within households and at markets, and essential item affordability, did not frequently differ. Self-determination of a severe economic impact may represent a relative change in the household's socioeconomic status from before the pandemic.