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The growing demand for biological therapeutics has increased interest in large‐volume perfusion bioreactors, but the operation and scalability of perfusion membranes remain a challenge. This study evaluates perfusion cell culture performance and monoclonal antibody (mAb) productivity at various membrane fluxes (1.5–5 LMH), utilizing polyvinylidene difluoride (PVDF), polyethersulfone (PES), or polysulfone (PS) membranes in tangential flow filtration mode. At low flux, culture with PVDF membrane maintained higher cell culture growth, permeate titer (1.06–1.34 g/L) and sieving coefficients (≥83%) but showed lower permeate volumetric throughput and higher transmembrane pressure (TMP) (>1.50 psi) in the later part of the run compared to cultures with PES and PS membrane. However, as permeate flux increased, the total mass of product decreased by around 30% for cultures with PVDF membrane, while it remained consistent with PES and PS membrane, and at the highest flux studied, PES membrane generated 12% more product than PVDF membrane. This highlights that membrane selection for large‐volume perfusion bioreactors depends on the productivity and permeate flux required. Since operating large‐volume perfusion bioreactors at low flux would require several cell retention devices and a complex setup, PVDF membranes are suitable for low‐volume operations at low fluxes whereas PES membranes can be a desirable alternative for large‐volume higher demand products at higher fluxes. [ABSTRACT FROM AUTHOR]

Due to its ability to improve the most frequent clinical sequelae left by ischemia, repetitive transcranial magnetic stimulation has been considered a promising therapeutic strategy for stroke. Those improvements are associated with changes in neurons and their synaptic liaisons. However, the hypothesis that this technique modulates astrocytes, potentiating their neuroprotective capabilities, was also raised. This study aims to identify the effects triggered by high‐frequency repetitive magnetic stimulation (HF‐rMS) on astrocytes that contribute to its neuroprotective effects. Neuron–glia and astrocyte cortical cultures subject to oxygen and glucose deprivation were used as an in vitro model of ischemia. Neuroprotection promoted by HF‐rMS was evaluated by analysis of markers of neuronal activity and morphometric analysis of neurons. Glial reactivity was determined by immunocytochemistry. The levels of growth factors in the astrocyte‐conditioned medium (CM) were assessed through a Growth Factor Array and glial‐derived neurotrophic factor (GDNF) expression was analyzed by RT‐PCR and Western blot. Our results show that neurons injured by ischemia can be rescued through the modulation of astrocytes by HF‐rMS. This modulation helps to maintain the number and length of neurites and increases the number of neurons expressing ERK1/2 and c‐Fos. Analysis of the astrocyte‐CM showed that HF‐rMS stimulated the release of several trophic factors by astrocytes. Moreover, GDNF was one of the released factors that contributed to the recovery mechanisms triggered by HF‐rMS. Our results show that modulation of astrocytes by HF‐rMS effectively rescues neurons injured by ischemia and suggest that by targeting astrocytes this approach can also be used to promote neuroprotection in other brain lesions. [ABSTRACT FROM AUTHOR]

Protein concentration determination is a necessary in‐process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off‐line to in‐line analysis. One solution to fulfill this process analytical technology need is an in‐line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor‐to‐sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in‐line IoR sensor for real‐time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing. [ABSTRACT FROM AUTHOR]

Summary: This paper describes statistical methodologies for removing the influence of operational effects from the dynamic responses of a telecommunications tower. The characterization of the dynamic responses of the structure, over a period of 3 months, was based on a continuous monitoring system that included accelerometers, anemometers and a meteorological station. The analysis of the results allowed identifying a significant number of critical events, for which the dynamic response under wind action is significantly amplified, as well as sporadic events, associated with high peak acceleration values, due to the influence of operational effects related to the movement of the lift, technical staff, and equipment. The automatic identification of critical events, based on extreme acceleration values, required the prior removal of operational effects from the records using two distinct methodologies, one based on the principal component analysis (PCA) and the other based on the crest factor (CF) and on autoregressive models (AR). Both methodologies showed efficiency and robustness in eliminating acceleration peaks due to operational effects; however, the methodology based on the CF and AR models proved to be computationally more efficient and resulted on a smaller number of false‐positive occurrences in the identification of critical events. The developed methodologies showed potential to be integrated in Structural Health Monitoring (SHM) systems to assess the structural safety and serviceability of telecommunications towers. [ABSTRACT FROM AUTHOR]

Although several compelling benefits for bioprocess intensification have been reported, the need for a streamlined integration of perfusion cultures with capture chromatography still remains unmet. Here, a robust solution is established by conducting tangential flow filtration‐based perfusion with a wide‐surface pore microfiltration membrane. The resulting integrated continuous bioprocess demonstrated negligible retention of antibody, DNA, and host cell proteins in the bioreactor with average sieving coefficients of 98 ± 1%, 124 ± 28%, and 109 ± 27%, respectively. Further discussion regarding the potential membrane fouling mechanisms is also provided by comparing two membranes with different surface pore structures and the same hollow fiber length, total membrane area, and chemistry. A cake‐growth profile is reported for the narrower surface pore, 0.65‐µm nominal retention perfusion membrane with final antibody sieving coefficients ≤70%. Whereas the sieving coefficient remained ≥85% during 40 culture days for the wide‐surface pore, 0.2‐µm nominal retention rating membrane. The wide‐surface pore structure, confirmed by scanning electron microscopy imaging, minimizes the formation of biomass deposits on the membrane surface and drastically improves product sieving. This study not only offers a robust alternative for integrated continuous bioprocess by eliminating additional filtration steps while overcoming sieving decay, but also provides insight into membranes' fouling mechanism. [ABSTRACT FROM AUTHOR]

Continuous countercurrent tangential chromatography (CCTC) enables steady‐state continuous bioprocessing with low‐pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest and postcapture polishing of mAb; however, these studies were performed with commercial chromatography resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20–25 µm) with lower cross‐linking was co‐developed with industrial partner Purolite and tested with CCTC. Due to increased binding capacity and faster kinetics, the resulting CCTC process showed more than a 2X increase in productivity, and a 2X reduction in buffer consumption over commercial protein A resins used in previous CCTC studies, as well as more than a 10X productivity increase versus conventional column operation. Single‐pass tangential flow filtration was integrated with the CCTC system, enabling simple control of eluate concentration. A scale‐up exercise was conducted to provide a quantitative comparison of CCTC and batch column chromatography. These results clearly demonstrate opportunities for using otherwise unpackable soft small particle size resins with CCTC as the core of a continuous bioprocessing platform. [ABSTRACT FROM AUTHOR]

As it is shown, this is a very low colorectal anastomosis; however it is important to have a loose and clean rectal stump to prevent tension and fat or muscle tissue from entering the anastomosis, respectively. The double-staple technique is a widely performed procedure for low anterior resection anastomosis, but it creates two points of intersection of the stapled lines, which are sites of structural fragility, predisposing to a greater risk of anastomotic leak. The video that we present here (Video S1) is intended to show an alternative to the performance of a laparoscopic single-staple anastomosis to avoid the intersection of the staple lines, with the execution of a zigzag suture in the rectal stump with 2/0 prolene. [Extracted from the article]

Bioprocess intensification can be achieved through high cell density perfusion cell culture with continuous protein capture integration. Protein passage and cell retention are commonly accomplished using tangential flow filtration systems consisting of microporous membranes. Significant challenges, including low efficiency and decaying product sieving over time, are commonly observed in these cell retention devices. Here, we demonstrate that a macroporous membrane overcomes the product sieving challenges when comparing to several other membrane chemistries and pore sizes within the microporous range. This way, variable chromatography column loading is avoided. The macroporous membrane yielded a 13,000 L/m2 volumetric throughput. The membrane's cut‐off size results in an increased permeate turbidity due to particles passage, such as cell debris, through pores ranging from 1 to 4 µm. In addition, successful chromatography column plugging mitigation was achieved by employing depth filtration before the chromatographic step. Depth filtration volumetric throughputs were between 600 and 1,000 L/m2. Combing a macroporous cell retention device with a depth filter not only provided an alternative to address the challenge of undesired long protein residence times in the bioreactor due to product sieving decay, but also exhibited a throughput increase, making the integration of multicolumn capture chromatography with a perfusion cell culture a more robust process. [ABSTRACT FROM AUTHOR]

Background: The health inequalities experienced by lesbian, gay, bisexual, trans and intersex (LGBTI) people are well documented with several reviews of global research summarizing key inequalities. These reviews also show how the health‐care needs of LGBTI people are often poorly understood whilst suggesting that targeted initiatives to reduce inequalities should involve LGBTI people. Objectives: To determine what is known about the health‐care inequalities faced by LGBTI people? What are the barriers faced by LGBTI people whilst accessing health care, and health professionals when providing care? What examples of promising practice exist? Design: Rapid reviews of grey literature were co‐produced with LGBTI people in 27 countries followed by a thematic analysis and synthesis across all data sets. The review included grey literature from each country that might not otherwise be accessible due to language barriers. Main results: Rapid reviews showed that LGBTI people faced various inequalities and barriers whilst accessing health care. Where heterosexuality, binary gender and assumed male/female sex characteristics were upheld as the norm, and where LGBTI people differed from these norms, discrimination could result. In consultations where LGBTI people feared discrimination and did not disclose their LGBTI status, health professionals lacked the information required for appropriate assessments. Conclusion: With greater understanding of sexual orientation (LGB people), gender identity (trans people) and sex characteristics (intersex people), combined with access to contemporary knowledge and training, health professionals can work in collaboration with researchers, policymakers and LGBTI people to develop systems that are better attuned to the needs of all service users. [ABSTRACT FROM AUTHOR]

Abstract: Background: One of the most significant challenges facing the provision of health care in present societies is the fact that the largest growing segment of the patient population is comprised of individual and culturally diverse people. However, the impact of this diversity on clinician–client interactions has only been examined recently. This study addresses the issues of culture and diversity in psychotherapy processes in Portugal. Methods: The study used an analogue experimental design, in a qualitative analogue study. The sample included 31 psychotherapists of varied years of experience and theoretical training background. Cultural diversity competences were measured with a semi‐structured interview, through case conceptualisation and intervention planning by watching four minute video case vignettes with stigmatised group clients (varying on migration background, religion, race and sexual orientation), and all female college students presenting the same complaint. Two cases (of four) were presented to each psychotherapist (at random, controlling for presentation order). Interviews addressed case conceptualisation of each of the clients, as well as questions on how the participants typically integrated diversity in psychotherapy practice. Transcripts of the interviews were analysed incorporating features of thematic content analysis and Consensual Qualitative Research. Findings: Results showed that awareness, knowledge and skills were identified mostly at a level of blindness (n = 519; 70.5%) and precompetence (n = 172; 23.5%), while only a few units of analysis were categorised as competent (n = 43; 6.0%). Conclusions: This study highlights the importance of individual and cultural diversity competence training for clinicians, particularly in Europe, given its current migratory context, and encourages the promotion of diversity‐sensitive approaches in mental health care. [ABSTRACT FROM AUTHOR]

ABSTRACT Purification processes for monoclonal Immunoglobulin G (IgG) typically employ protein A chromatography as a capture step to remove most of the impurities. One major concern of the post-protein A chromatography processes is the co-elution of some of the host cell proteins (HCPs) with IgG in the capture step. In this work, a novel method for IgG elution in protein A chromatography that reduces the co-elution of HCPs is presented where a two-step pH gradient is self-formed inside a protein A chromatography column. The complexities involved in using an internally produced pH gradient in a protein A chromatography column employing adsorbed buffering species are discussed though equation-based modeling. Under the conditions employed, ELISA assays show a 60% reduction in the HCPs co-eluting with the IgG fraction when using the method as compared to conventional protein A elution without affecting the IgG yield. Evidence is also obtained which indicates that the amount of leached protein A present in free solution in the purified product is reduced by the new method. Biotechnol. Bioeng. 2017;114: 154-162. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Summary: This article describes the experimental evaluation of the dynamic effects induced by wind on a high‐rise telecommunications tower based on a permanent monitoring system. Monte da Virgem telecommunications tower is located near the city of Porto (Portugal), and its structure consists in a reinforced concrete shaft and a steel mast, with a total height of 177 m. The monitoring system includes accelerometers, anemometers, and a meteorological station, allowing the characterization of the maximum accelerations of the structure and wind regimes during a period of 6 months. The analysis of the results enabled identifying specific events, denominated as critical events, for which the dynamic response of the tower under wind actions appears significantly amplified due to wind aeroelastic instability phenomena in the steel mast. The automatic identification of the critical events was based on the application to the acceleration's records of an autoregressive model and estimation of its optimal order number based on a singular value decomposition. The results proved the robustness and efficiency of the proposed technique in identifying the number, duration, and maximum amplitude of accelerations associated to the critical events, envisaging its potential integration in structural health monitoring systems. [ABSTRACT FROM AUTHOR]

Introduction Consistent use of PrEP reduces HIV transmission from sexual practices amongst men who have sex with men (MSM) up to 92% []. Lisbon MSM cohort study estimates point that 59.3% of their participants at entrance (1593 HIV negative MSM enrolled between April 2011 and May 2013) were eligible for PrEP [], according to the 2014 USA PrEP guidelines []. Studies about PrEP acceptability and implementation support policies aimed at increasing and rolling out its use. Hence, the exploratory study about PrEP acceptability in MSM at Lisbon. Materials and Methods A street-based intercept survey, adapted from Mantell et al. study [], was the one used on MSM attending the 2014 Lisbon pride fair. The survey included socio-demographic data, PrEP awareness and readiness to use it, probability of MSM's social network to also use it, promptness to join PrEP-related studies, type of PrEP warranted and condomless anal sex practice in the last six months. Results A total of 110 HIV negative Portuguese MSM responded, with a median age of 33% and 84% of them identified themselves as gay. A majority of MSM were unaware of PrEP (59%); those that were aware, had heard of it trough CheckpointLx (31%), internet (22%) or health professionals (20%). 66% were likely or very likely to participate in PrEP-related studies. 57% of MSM were likely or very likely to use PrEP if available and reported that some, if not almost all of their social network, will do it too (70%). Type of PrEP preferred was oral, a pill a day (43%), followed by oral, intermittent intake (32%). Overall 41% of MSM had condomless anal sex practice in the last six months. Conclusions In this MSM Portuguese sample, a general willingness to adopt PrEP was predominant, specially the oral daily intake. Forty-one percent of participants had had condomless anal sex practice in the last six months and therefore fitted within the criteria to be on Pre-Exposure Prophylaxis (PrEP), according to MSM Risk Index in 2014 USA PrEP guidelines. PrEP, when available in Portugal, should be a powerful tool for HIV prevention in this key population. [ABSTRACT FROM AUTHOR]