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There is increasing recognition regarding the potential of Higher Education Institutions (HEIs) to be significant Anchor institutions capable of impacting the wellbeing of the local communities where they are situated. Subsequently, more universities are prioritising their social and civic responsibility by embedding a research ethos based on closer engagement with their locality, within their key institutional processes. However, demonstrating the social value of community engagement in a meaningful way is difficult, particularly the type of intangible benefits such as relationship building and co-production of knowledge that are forged through collaboration. We present results of a pilot study which applied a Socially Modified Economic Valuation (SMEV) approach to three very different case study projects within a University-Community partnership initiative situated in Belfast, Northern Ireland, to help evaluate how well the university’s civic and social obligations are being fulfilled. Two sets of potential social weights were derived. The first was based on the official Deprivation Index and the second on a combination of desirable ‘social’ and ‘strategy’ goals. Findings showed that the social valuation element of SMEV may potentially be crucially important in assisting with nuanced interpretation of social value across different communities in different places.

Abstract Membrane fouling significantly reduces membrane permeability, leading to higher operational expenses. In situ monitoring of membrane fouling can potentially be used to reduce operation cost by optimizing operational parameters and cleaning conditions. In this study, a platinum wire with a diameter of 20 µm was attached to the surface of a ceramic ultrafiltration membrane, and by measuring the voltage across the wire while applying an AC current, the amplitude of the third harmonic wave, the so-called 3ω signal, was obtained. Results showed increasing 3ω signals during formation of fouling layers, which correlates directly to the hydraulic resistance of the formed fouling layer in semi-dead end filtration of polymeric core shell particles and crossflow filtration of diluted milk. This is explained by the insulating effect of the fouling layers which reduces heat convection by crossflow and the different thermal conductivity in the fouling layer compared with the feed. After membrane cleaning, the permeability and the magnitude of the 3ω signal were partly restored, showing that the 3ω method can be used to monitor the effect of cleaning. The frequency of the AC current was varied so it was possible to measure the heat conductivity in the fouling layer (high frequency) and heat convection due to cross-flow (low frequency). This may potentially be used to get information of the type of fouling (heat conductivity) and thickness of the fouling layer (AC frequency where heat conductivity becomes dominating).

Abstract Background Preterm infants have a risk of health and developmental problems emerging after discharge. This indicates the need for a comprehensive follow-up to enable early identification of these problems. In this paper, we introduce a follow-up tool “ePIPARI – web-based follow-up for preterm infants”. Our future aim is to investigate whether ePIPARI is a feasible tool in the follow-up of preterm infants and whether it can identify children and parents in need of clinical interventions. Methods ePIPARI includes eight assessment points (at term age and at 1, 2, 4, 8, 12, 18, and 24 months of corrected age) when the child´s health and growth, eating and feeding, neurodevelopment, and parental well-being are evaluated. ePIPARI consists of several widely used, standardized questionnaires, in addition to questions typically presented to parents in clinical follow-up visits. It also provides video guidance and written information about age-appropriate neurodevelopment for the parents. Parents of children born before 34 weeks of gestation during years 2019–2022 are being invited to participate in the ePIPARI study, in which web-based follow-up with ePIPARI is compared to clinical follow-up. In addition, the parents of children born before 32 weeks of gestation, who reached the corrected age of two years during 2019–2021 were invited to participate for the assessment point of 24 months of ePIPARI. The parents are asked to fill in the online questionnaires two weeks prior to each clinical follow-up visit. Discussion The web-based tool, ePIPARI, was developed to acquire a sensitive and specific tool to detect infants and parents in need of further support and clinical interventions. This tool could allow individualized adjustments of the frequency and content of the clinical visits. Trial registration ClinicalTrials.cov, NCT05238168 . Registered 11 April 2022 – Retrospectively registered.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit a (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In [COPA.sup.R1142X] and [COPA.sup.R1058C] fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-[kappa]B signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling., Introduction The COPA gene encodes coatomer protein complex subunit [alpha] (COPA) (1). COPA was described in 1991 as a coat subunit of Golgi derived non-clathrin-coated vesicles, later termed 'coatomer' (2, [...]

Objectives: This study aimed to investigate the evolution of Plasmodium falciparum antimalarial drug resistance markers by comparing the pre- and post-adoption of artemisinin-based combination therapies (ACTs) in Yaounde, Cameroon. Methods: The molecular characterization of known antimalarial drug resistance markers (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and Pfk13) in P. falciparum-positive samples collected in 2014 and 2019-2020 was achieved using nested polymerase chain reaction, followed by targeted amplicon deep sequencing on the Illumina MiSeq platform. Data derived were compared with those published during the pre-ACT adoption period from 2004 to 2006. Results: A high prevalence of Pfmdr1 184F, Pfdhfr 51I/59R/108N, and Pfdhps 437G mutant alleles was observed during the post-ACT adoption period. The Pfcrt 76T and Pfmdr1 86Y mutant alleles significantly declined between 2004 and 2020 (P

Abstract Background The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab. Methods From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups. Results BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36–4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25–0.80) and BCSS (aHR 0.46, 95% CI 0.24–0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes. Conclusions In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

Background: In general, migrant women have a lower breast cancer (BC) incidence rate and higher BC mortality than autochthonous women. Further, migrant women show lower participation in the national BC screening program. To further investigate those aspects, we aimed to determine differences in incidence and tumor characteristics between autochthonous and migrant BC patients in Rotterdam, the Netherlands. Methods: We selected women diagnosed with BC in Rotterdam during 2012–2015 from the Netherlands Cancer Registry. Incidence rates were calculated by migrant status (i.e., women with or without migration background). Multivariable analyses revealed adjusted odds ratios (OR) and 95% confidence intervals (CI) on the association between migration status and patient and tumor characteristics, additionally stratified by screening attendance (yes/no). Results: In total 1372 autochthonous and 450 migrant BC patients were included for analysis. BC incidence was lower among migrants than among autochthonous women. Overall, migrant women were younger at BC diagnosis (53 vs. 64 years, p

[Propósito] O Novo Marco Legal do Saneamento Básico promoveu alterações significativas na Lei Federal nº 11.445/2007, dentre as quais previu-se o dever de os contratos de prestação de serviços de saneamento básico definirem metas que assegurem o atendimento de 99% da população com água potável e de 90% da população com coleta e tratamento de esgotos até 31 de dezembro de 2033. Para as empresas estatais, que hoje são responsáveis pela execução dos serviços de água e esgoto em aproximadamente 77% dos municípios brasileiros, a aferição da capacidade econômico-financeira e o aditamento dos contratos de programa para incorporação das novas metas representa um desafio tanto para os titulares dos serviços quanto para as próprias empresas, tendo em vista as peculiaridades dessa forma de prestação e dos contratos de programa, os quais estão, em regra, inseridos em uma prestação regionalizada dos serviços, com a prática do subsídio cruzado e de uma estrutura tarifária única para diversos municípios. [Metodologia/abordagem/design] Para analisar a possibilidade de incorporação das novas metas de universalização, deverá ser levado em conta o contexto em que os contratos de programa estão inseridos, bem como a superação dos entraves relacionados às medidas de reequilíbrio econômico-financeiro, como a vedação da prorrogação da vigência dos contratos de programa e a resistência política na definição de novos valores tarifários, de modo que a incorporação das novas metas de universalização seja concomitante à garantia do equilíbrio contratual, atendendo ao público com a prestação de um serviço eficiente, universal e com tarifas adequadas. [Resultados] Vislumbra-se um cenário incerto e de muita dificuldade para os contratos de programa existentes e para as próprias empresas estatais

Abstract Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.

Background and Purpose: Hippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT. Materials and Methods: HS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation. Results: The median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p

Currently there is a global lack of consensus about the best treatment for asymptomatic congenital pulmonary airway malformation (CPAM) patients. The somatic KRAS mutations commonly found in adult lung cancer combined with mucinous proliferations are sometimes found in CPAM. For this risk of developing malignancy, 70% of paediatric surgeons perform a resection for asymptomatic CPAM. In order to stratify these patients into high- and low-risk groups for developing malignancy, a minimally invasive diagnostic method is needed, for example targeted molecular imaging. A prerequisite for this technique is a cell membrane bound target. The aim of this study was to review the literature to identify potential targets for molecular imaging in CPAM patients and perform a first step to validate these findings. A systematic search was conducted to identify possible targets in CPAM and adenocarcinoma in situ (AIS) patients. The most interesting targets were evaluated with immunofluorescent staining in adjacent lung tissue, KRAS+ CPAM tissue and KRAS– CPAM tissue. In 185 included studies, 143 possible targets were described, of which 20 targets were upregulated and membrane-bound. Six of them were also upregulated in lung AIS tissue (CEACAM5, E-cadherin, EGFR, ERBB2, ITGA2 and MUC1) and as such of possible interest. Validating studies showed that MUC1 is a potential interesting target. This study provides an extensive overview of all known potential targets in CPAM that might identify those patients at risk for malignancy and conducted the first step towards validation, identifying MUC1 as the most promising target.