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Abstract Three dimensional sensing is essential in order that machines may operate in and interact with complex dynamic environments. Solid-state beam scanning devices are seen as being key to achieving required system specifications in terms of sensing range, resolution, refresh rate and cost. Integrated optical phased arrays fabricated on silicon wafers are a potential solution, but demonstrated devices with system-level performance currently rely on expensive widely tunable source lasers. Here, we combine silicon nitride photonics and micro-electromechanical system technologies, demonstrating the integration of an active photonic beam-steering circuit into a piezoelectric actuated micro cantilever. An optical phased array, operating at a wavelength of 905 nm, provides output beam scanning over a range of 17° in one dimension, while the inclination of the entire circuit and consequently the angle of the output beam in a second dimension can be independently modified over a range of up to 40° using the piezoelectric actuator.

Summary: Our understanding and management of reproductive health and related disorders such as infertility, menstrual irregularities, and pituitary disorders depend on understanding the intricate sex-specific mechanisms governing prolactin secretion. Using ex vivo experiments in acute slices, in parallel with in vivo calcium imaging (GRIN lens technology), we found that dopamine neurons inhibiting PRL secretion (TIDA), organize as functional networks both in and ex vivo. We defined an index of efficiency of networking (Ieff) using the duration of calcium events and the ability to form plastic economic networks. It determined TIDA neurons’ ability to inhibit PRL secretion in vivo. Ieff variations in both sexes demonstrated TIDA neurons’ adaptability to physiological changes. A variation in the number of active neurons contributing to the network explains the sexual dimorphism in basal [PRL]blood secretion patterns. These sex-specific differences in neuronal activity and network organization contribute to the understanding of hormone regulation.

The karyotype of the IUCN least concern red-backed toadlet Pseudophryne (P.) coriacea (Keferstein, 1868) from the New South Wales Central Coast is described following tissue culture of toe clipping macerates and conventional DAPI staining. The diploid number is 2n = 24. The karyotype is represented by six large and five small chromosomal pairs and one very small chromosomal pair. The very small chromosome 12 is 12% the size of chromosome 1. One of the large chromosomes is subtelocentric, two of the large chromosomes are submetacentric and the remaining chromosomes are metacentric. The putative nucleolus organiser region (NOR) is observed on chromosome 4. The diploid number and location of the putative NOR correlates to that of the previously published IUCN critically endangered P. corroboree (Moore 1953) and unpublished descriptions of the P. coriacea karyotype. This is the first described cell culture of a species from the genus Pseudophryne Fitzinger, 1843, first published analysis of the P. coriacea karyotype and the first published analysis of centromeric allocation of this genus. Globally there exists a large inventory of tissue samples in cryobanks that are not associated with known recovery mechanisms such as basic cell culture techniques. Detailed cytogenetic analyses of these cryobanked samples are therefore not possible. This work therefore enables: (i) a comparison of the P. coriacea karyotype with that of the critically endangered P. corroboree and (ii) a benchmark for repeat and future cytogenetic and genomic analyses of cryostored samples of this genus.

Many cognitive problems can be decomposed into series of subproblems that are solved sequentially by the brain. When subproblems are solved, relevant intermediate results need to be stored by neurons and propagated to the next subproblem, until the overarching goal has been completed. We will here consider visual tasks, which can be decomposed into sequences of elemental visual operations. Experimental evidence suggests that intermediate results of the elemental operations are stored in working memory as an enhancement of neural activity in the visual cortex. The focus of enhanced activity is then available for subsequent operations to act upon. The main question at stake is how the elemental operations and their sequencing can emerge in neural networks that are trained with only rewards, in a reinforcement learning setting. We here propose a new recurrent neural network architecture that can learn composite visual tasks that require the application of successive elemental operations. Specifically, we selected three tasks for which electrophysiological recordings of monkeys' visual cortex are available. To train the networks, we used RELEARNN, a biologically plausible four-factor Hebbian learning rule, which is local both in time and space. We report that networks learn elemental operations, such as contour grouping and visual search, and execute sequences of operations, solely based on the characteristics of the visual stimuli and the reward structure of a task. After training was completed, the activity of the units of the neural network elicited by behaviorally relevant image items was stronger than that elicited by irrelevant ones, just as has been observed in the visual cortex of monkeys solving the same tasks. Relevant information that needed to be exchanged between subroutines was maintained as a focus of enhanced activity and passed on to the subsequent subroutines. Our results demonstrate how a biologically plausible learning rule can train a recurrent neural network on multistep visual tasks.

Abstract Background A significant proportion of Canadian adults is impacted by chronic noncommunicable diseases. These conditions may be improved by peer-led health promotion interventions that target modifiable risk factors; however, to date, there is mixed evidence on the effectiveness of these interventions. Unlike other health promotion programs, Hans Kai is grounded in a holistic model of health that simultaneously addresses multiple determinants of health at different levels of human ecology. In Hans Kai, a set of informational sessions that are delivered in a group setting by healthcare professionals are followed by regular peer-led group meetings in a self-governed support group setting that is designed to promote implementation of newly learned health competences. The Hans Kai trial described here aims to evaluate the efficacy of the Hans Kai program in promoting the health and wellbeing of its participants and investigate the experiences of the Hans Kai participants and facilitators. Methods This research will involve a mixed methods trial combining an experimental component with a qualitative component. The experimental component will involve a 6-month 2-group parallel superiority randomized controlled trial (RCT) in which 105 participants will be randomly assigned to two conditions, an intervention group (n = 70) that will participate in the Hans Kai program and a control group (n = 35) that will have access to standard care using a computer-generated random sequence; blinding will not occur. The RCT will test the impact of the program on several health outcomes and will be followed by a 12–18-month observational follow-up study that will provide data on the long-term durability of the 6-month RCT health outcomes. The qualitative component will investigate the experiences of program participants (n = 30) and facilitators (n = 15) to identify the main strengths and limitations of Hans Kai, uncover potential implementation issues, and elucidate the mechanisms through which the program works. The population of interest will include adults aged 18 + with or without chronic health conditions who self-report an interest in taking control of their own health and improving their lifestyle. In the RCT, all outcomes of interest will be measured using a multi-method approach, involving self-report questionnaires and objective indicators, and within-subject mean changes in outcomes over time between the two groups will be compared to address the RCT aims. Similarly, in the qualitative component, a multi-method approach, involving in-depth individual interviews, photovoice, and online surveys, will be used to reach a deeper and more nuanced understanding of the program strengths, how the program works, and for which people it is more effective. Adaptable components of the program will also be investigated and modified according to the feedback provided by the RCT participants. In the mixed methods integration of evidence, the qualitative findings will be used to explain the quantitative RCT results. Discussion The RCT findings will help support the further development and use of Hans Kai as well as other peer-led health promotion interventions. Trial registration United Stated Clinical Trial Registry ClinicalTrials.gov (registration# NCT03949725; Protocol version 2, June 22nd, 2022).

Abstract Background Potassium regulation in the body is primarily done in the kidney. In addition to this, hyperkalemia, occurs in approximately 10% of individuals with chronic kidney disease (CKD) and is associated with elevated all-cause mortality. Individuals with CKD are often told to restrict dietary potassium (K), however, this recommendation is based on low quality evidence. Reduced quality of life, limited dietary choices and nutritional deficiencies are all potential negative outcomes that may occur when restricting dietary K in CKD patients. There is a need for randomized controlled trials investigating the impact of dietary K modification on serum K concentrations in people with CKD. Methods A randomized 2-period crossover design comparing a liberalized K fruit and vegetable diet where participants will be required to consume ~ 3500 mg of dietary K daily, to a standard K restricted diet where participants will be required to consume

Abstract Background Monepantel is an anti‐helminthic drug that also has anti‐cancer properties. Despite several studies over the years, the molecular target of monepantel in mammalian cells is still unknown, and its mechanism‐of‐action is not fully understood, though effects on cell cycle, mTOR signalling and autophagy have been implicated. Methods Viability assays were performed on >20 solid cancer cell cells, and apoptosis assays were performed on a subset of these, including 3D cultures. Genetic deletion of BAX/BAK and ATG were used to establish roles of apoptosis and autophagy in killing activity. RNA‐sequencing was performed on four cell lines after monepantel treatment, and differentially regulated genes were confirmed by Western blotting. Results We showed that monepantel has anti‐proliferative activity on a broad range of cancer cell lines. In some, this was associated with induction of apoptosis which was confirmed using a BAX/BAK‐deficient cell line. However, proliferation is still inhibited in these cells following monepantel treatment, indicating cell‐cycle disruption as the major anti‐cancer effect. Previous studies have also indicated autophagic cell death occurs following monepantel treatment. We showed autophagy induction in multiple cell lines; however, deletion of a key autophagy regulator ATG7 had minimal impact on monepantel’s anti‐proliferative activity, suggesting autophagy is associated with, but not required for its anti‐tumour effects. Transcriptomic analysis of four cell lines treated with monepantel revealed downregulation of many genes involved in the cell cycle, and upregulation of genes linked to ATF4‐mediated ER stress responses, especially those involved in amino‐acid metabolism and protein synthesis. Conclusions As these outcomes are all associated with mTOR signalling, cell cycle and autophagy, we now provide a likely triggering mechanism for the anti‐cancer activity of monepantel.

Abstract Background Hypertensive disorders of pregnancy are a leading cause of maternal and fetal morbidity and mortality and a significant risk factor for future cardiovascular disease development in women. This study aimed to explore lifestyle wellness-related variables and how they impact the risk of hypertension in pregnancy. Methods This is a secondary analysis of data from the prospective cohort study Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b). Data was collected through questionnaires, clinical evaluations, and medical records review at 8 academic medical centers in the United States. Four study visits were scheduled throughout the participant’s pregnancy (visits one–four): 60–136, 160–216, and 220–296 weeks gestation and birth. A series of statistical modeling and logistical regression were performed using 15 lifestyle variables related to sleep, nutrition, resilience, illness avoidance, and physical activity were selected as predictor variables with an outcome variable of hypertension. Results Of 9289 nulliparous participants considered for inclusion in our analyses, 1464 had any HDP during study participation, and 554 participants had complete data available for the study and were included in our final sample. Results were statistically significant at a level of p

Gonadotropes in the pituitary secrete follicle-stimulating hormone and luteinizing hormone to control gonadal function and fertility, but whether they exert actions on extra-gonadal organs is not fully understood. Here the authors report that gonadotropes regulate liver steatosis independent of the ovaries in mice.

Background: Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective: This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design: A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting: Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants: Adult participants with G3-G5 CKD and metabolic acidosis. Measurements: Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods: A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations: Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions: This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration: This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Abstract Background Neurons are highly specialized cells with a complex morphology generated by various membrane trafficking steps. They contain Golgi outposts in dendrites, which are formed from somatic Golgi tubules. In trafficking membrane fusion is mediated by a specific combination of SNARE proteins. A functional SNARE complex contains four different helices, one from each SNARE subfamily (R-, Qa, Qb and Qc). Loss of the two Qb SNAREs vti1a and vti1b from the Golgi apparatus and endosomes leads to death at birth in mice with massive neurodegeneration in peripheral ganglia and defective axon tracts. Methods Hippocampal and cortical neurons were isolated from Vti1a −/− Vti1b −/− double deficient, Vti1a −/− Vti1b +/− , Vti1a +/− Vti1b −/− and Vti1a +/− Vti1b +/− double heterozygous embryos. Neurite outgrowth was determined in cortical neurons and after stimulation with several neurotrophic factors or the Rho-associated protein kinase ROCK inhibitor Y27632, which induces exocytosis of enlargeosomes, in hippocampal neurons. Moreover, postsynaptic densities were isolated from embryonic Vti1a −/− Vti1b −/− and Vti1a +/− Vti1b +/− control forebrains and analyzed by western blotting. Results Golgi outposts were present in Vti1a −/− Vti1b +/− and Vti1a +/− Vti1b −/− dendrites of hippocampal neurons but not detected in the absence of vti1a and vti1b. The length of neurites was significantly shorter in double deficient cortical neurons. These defects were not observed in Vti1a −/− Vti1b +/− and Vti1a +/− Vti1b −/− neurons. NGF, BDNF, NT-3, GDNF or Y27632 as stimulator of enlargeosome secretion did not increase the neurite length in double deficient hippocampal neurons. Vti1a −/− Vti1b −/− postsynaptic densities contained similar amounts of scaffold proteins, AMPA receptors and NMDA receptors compared to Vti1a +/− Vti1b +/− , but much more TrkB, which is the receptor for BDNF. Conclusion The absence of Golgi outposts did not affect the amount of AMPA and NMDA receptors in postsynaptic densities. Even though TrkB was enriched, BDNF was not able to stimulate neurite elongation in Vti1a −/− Vti1b −/− neurons. Vti1a or vti1b function as the missing Qb-SNARE together with VAMP-4 (R-SNARE), syntaxin 16 (Qa-SNARE) and syntaxin 6 (Qc-SNARE) in induced neurite outgrowth. Our data show the importance of vti1a or vti1b for two pathways of neurite elongation.

This paper presents the thermal behavior of non-resonant (quasi-static) piezoelectric biaxial MEMS scanners with Bragg reflectors. These scanners were developed for LIDAR (LIght Detection And Ranging) applications using a pulsed 1550 nm laser with an average power of 2 W. At this power, a standard metal (gold) reflector can overheat and be damaged. The Bragg reflector developed here has up to 24 times lower absorption than gold, which limits heating of the mirror. However, the use of such a reflector involves a technological process completely different from that used for gold and induces, for example, different final stresses on the mirror. In view of the high requirements for optical power, the behavior of this reflector in the event of an increase in temperature needs to be studied and compared with the results of previous studies using gold reflectors. This paper shows that the Bragg reflector remains functional as the temperature rises and undergoes no detrimental deformation even when heated to 200 °C. In addition, the 2D-projection model revealed a 5% variation in optical angle at temperatures up to 150 °C and stability of 2D scanning during one hour of continuous use at 150 °C. The results of this study demonstrate that a biaxial piezoelectric MEMS scanner equipped with Bragg reflector technology can reach a maximum temperature of 150 °C, which is of the same order of magnitude as can be reached by scanners with gold reflectors.

IntroductionWith the prevalence of obesity increasing, many weight-loss programs were created to aid in combating the trend. The Weight Loss Clinic (WLC) was created to provide personalized support for lifestyle changes using a multidisciplinary team with medical oversight. This study evaluated the clinically-managed weight loss program at the Wellness Institute.MethodsThis was a prospective evaluation of a newly established program between January 2019–August 2020. Participants who entered the weight loss program were approached to learn about the evaluation. A total of 41 participants were included. The primary outcomes included changes in body weight and achievement of more than 5% initial body weight loss. Outcome measures were collected pre-and post-program and the data was analyzed through paired t-tests on R studio.ResultsGreater body weight-loss was seen in completers pre-COVID-19 compared to those who completed during the pandemic (Mean, ±SD; 7.51 ± 6.24 kg n = 13 p

Summary: Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca2+ indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca2+]i transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca2+ channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca2+ subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals.

Abstract Duchenne muscular dystrophy is a severe neuromuscular disease causing a progressive muscle wasting due to mutations in the DMD gene that lead to the absence of dystrophin protein. Adeno-associated virus (AAV)-based therapies aiming to restore dystrophin in muscles, by either exon skipping or microdystrophin expression, are very promising. However, the absence of dystrophin induces cellular perturbations that hinder AAV therapy efficiency. We focused here on the impact of the necrosis-regeneration process leading to nuclear centralization in myofiber, a common feature of human myopathies, on AAV transduction efficiency. We generated centronucleated myofibers by cardiotoxin injection in wild-type muscles prior to AAV injection. Intramuscular injections of AAV1 vectors show that transgene expression was drastically reduced in regenerated muscles, even when the AAV injection occurred 10 months post-regeneration. We show also that AAV genomes were not lost from cardiotoxin regenerated muscle and were properly localised in the myofiber nuclei but were less transcribed leading to muscle transduction defect. A similar defect was observed in muscles of the DMD mouse model mdx. Therefore, the regeneration process per se could participate to the AAV-mediated transduction defect observed in dystrophic muscles which may limit AAV-based therapies.

Abstract Background Rheumatic and musculoskeletal diseases (RMD) are associated with depression, fatigue, and disturbed sleep – symptoms that often impact behavior and activity. Patient reported outcomes (PROs) are a way of collecting information on the patient symptom experience directly from the individual. The purpose of this study was to measure and compare user smartphone sensor and activity data in adults with RMDs and assess associations with PROs. Methods We invited adults with RMDs enrolled in the FORWARD Databank to participate by installing a custom app on their smartphone and answering PROs (pain, global, HAQ-II) questions daily and weekly over 3 years. Passive data collected included mobility distance, unique calls and text messages, call durations, and number of missed calls. Confounders included sociodemographic, clinical, passive phone behavior, and seasonal factors. Kappa statistics between PRO and flares were computed to measure agreement. The agreement between daily and weekly VAS pain was estimated using the intraclass (ICC) correlation of a two-way random effect model. The relationship between the weekly PRO outcomes and the passive phone data was analyzed with a linear mixed-effect model (LMM), including a random intercept for participant and slope for time in the study with an unstructured covariate structure. Results Of the 446 participants, the mean (SD) age was 54 (12) years, most (65.5%) had rheumatoid arthritis (RA), the vast majority (91%) were female, and the US Northeast has the least representation (12%). Longer reaction times, interaction diversity, and higher mobility were associated with worse PROs while longer text messages were associated with better PROs. Participants in this study showed good levels of adherence which holds promise for future interventions using passive behavior measures in self-management and clinical follow-up. Conclusion This is the first study to examine passive smartphone behavior with PROs in RMDs and we found significant associations between these behaviors and important health outcomes of pain and function. As smartphone usage continues to change, future studies should validate and expand on our findings with a goal of finding changes in patient symptoms passively through mobile device monitoring.

With emerging resistance to frontline treatments, it is vital that new antimalarial drugs are identified to target Plasmodium falciparum. We have recently described a compound, MMV020291, as a specific inhibitor of red blood cell (RBC) invasion, and have generated analogues with improved potency. Here, we generated resistance to MMV020291 and performed whole genome sequencing of 3 MMV020291-resistant populations. This revealed 3 nonsynonymous single nucleotide polymorphisms in 2 genes; 2 in profilin (N154Y, K124N) and a third one in actin-1 (M356L). Using CRISPR-Cas9, we engineered these mutations into wild-type parasites, which rendered them resistant to MMV020291. We demonstrate that MMV020291 reduces actin polymerisation that is required by the merozoite stage parasites to invade RBCs. Additionally, the series inhibits the actin-1-dependent process of apicoplast segregation, leading to a delayed death phenotype. In vitro cosedimentation experiments using recombinant P. falciparum proteins indicate that potent MMV020291 analogues disrupt the formation of filamentous actin in the presence of profilin. Altogether, this study identifies the first compound series interfering with the actin-1/profilin interaction in P. falciparum and paves the way for future antimalarial development against the highly dynamic process of actin polymerisation.

Central integration of peripheral appetite-regulating signals ensures maintenance of energy homeostasis. Thus, plasticity of circulating molecule access to neuronal circuits involved in feeding behavior plays a key role in the adaptive response to metabolic changes. However, the mechanisms involved remain poorly understood despite their relevance for therapeutic development. Here, we investigated the role of median eminence mural cells, including smooth muscle cells and pericytes, in modulating gut hormone effects on orexigenic/anorexigenic circuits. We found that conditional activation of median eminence vascular cells impinged on local blood flow velocity and altered ghrelin-stimulated food intake by delaying ghrelin access to target neurons. Thus, activation of median eminence vascular cells modulates food intake in response to peripheral ghrelin by reducing local blood flow velocity and access to the metabolic brain.

Background: People living with chronic kidney disease (CKD) have identified diet as an important aspect of their life and care. Understanding current consumption patterns in this population, and how they relate to patient perspectives of dietary recommendations, may help identify and design potential dietary intervention strategies in CKD. Objective: To investigate the dietary intake patterns of people with advanced-stage CKD, as well as subjective perspectives regarding dietary recommendations from participants and their caregivers. Design: Mixed-methods study with a sequential explanatory design. Setting: Manitoba, Canada. Participants: Individuals with late-stage CKD (CKD stages G4-G5, including dialysis) participating in the Canadian Frailty Observation and Interventions Trial (CanFIT). Methods: First, quantitative data were collected via a cross-sectional dietary assessment, using three 24-hour dietary recalls, a 36-question short diet questionnaire (SDQ), and a Nutrition Quality of Life (NQoL) tool (n = 59). Second, qualitative data were collected during 2 focus groups ( n 1 = 12 and n 2 = 7) held with a subsample of individuals who had completed the dietary surveys, along with their caregivers. Focus groups explored topics related to diet and CKD; transcribed data were analyzed thematically. In the interpretation stage, the qualitative findings were combined with the quantitative results to help explain the latter and reach a deeper understanding of the subjective experiences of adults with CKD. Results: Quantitatively, nearly all (48/51; 94%) participants (mean age 70.8 ± 10.8 years) reported energy intakes below recommendations and most (86%) did not achieve recommended fiber intake. In addition, 15/21 (71%) of patients on dialysis had low protein intake. Qualitatively, 2 themes were identified: (1) Lacking/Needing dietary guidance—incomplete “information overload,” and (2) Experiencing difficulty in adapting to restrictions. Within the former theme, participants spoke of getting too much information at once, often at the wrong time. Within the latter theme, participants spoke of a loss of appetite, and cheating on their dietary recommendations. Limitations: Potential recall bias recalling dietary patterns, small sample size limiting generalizability, self-selection bias. Conclusion: Despite the reported lifestyle changes made by individuals with CKD, which negatively impacted their lives, many had suboptimal nutrition, especially in terms of energy and fiber. In addition, those on dialysis were not eating enough protein, which could be due to changing dietary recommendations as CKD progresses. Qualitative findings provided additional insight into how requisite CKD-dietary changes were perceived and how participants coped with these changes. The timing and delivery of the dietary education within CKD care in Manitoba may not be working for people with CKD as they progress through the disease.

Abstract Background Chronic kidney disease (CKD) is associated with a reduced quality of life and an increased risk of kidney failure, cardiovascular events, and all-cause mortality. Accumulation of nitrogen-based uremic toxins leads to worsening of symptoms in individuals with CKD. Many uremic toxins, such as indoxyl and p-cresol sulphate, are produced exclusively by the gut microbiome through the proteolytic digestion of aromatic amino acids. Strategies to reduce the production of these toxins by the gut microbiome in individuals with CKD may lessen symptom burden and delay the onset of dialysis. One such strategy is to change the overall metabolism of the gut microbiome so that less uremic toxins are produced. This can be accomplished by manipulating the energy source available to the microbiome. Fermentable carbohydrates which reach the gut microbiome, like resistant starch (RS), have been shown to inhibit or reduce bacterial amino acid metabolism. This study aims to investigate the effects of resistant potato starch (RPS) as a prebiotic in individuals with CKD before the onset of dialysis. Methods This is a double-blind, randomized two-period crossover trial. Thirty-six eligible participants will consent to follow a 26-week study regimen. Participants will receive 2 sachets per day containing either 15 g of RPS (MSPrebiotic, resistant potato starch treatment) or 15 g cornstarch (Amioca TF, digestible starch control). Changes in blood uremic toxins will be investigated as the primary outcome. Secondary outcomes include the effect of RPS consumption on symptoms, quality of life and abundance, and diversity and functionality of the gut microbiome. Discussion This randomized trial will provide further insight into whether the consumption of RPS as a prebiotic will reduce uremic toxins and symptoms in individuals who have CKD. Trial registration ClinicalTrials.gov NCT04961164 . Registered on 14 July 2021

This paper presents the fabrication and characterization of a biaxial MEMS (MicroElectroMechanical System) scanner based on PZT (Lead Zirconate Titanate) which incorporates a low-absorption dielectric multilayer coating, i.e., a Bragg reflector. These 2 mm square MEMS mirrors, developed on 8-inch silicon wafers using VLSI (Very Large Scale Integration) technology are intended for long-range (>100 m) LIDAR (LIght Detection And Ranging) applications using a 2 W (average power) pulsed laser at 1550 nm. For this laser power, the use of a standard metal reflector leads to damaging overheating. To solve this problem, we have developed and optimised a physical sputtering (PVD) Bragg reflector deposition process compatible with our sol-gel piezoelectric motor. Experimental absorption measurements, performed at 1550 nm and show up to 24 times lower incident power absorption than the best metallic reflective coating (Au). Furthermore, we validated that the characteristics of the PZT, as well as the performance of the Bragg mirrors in terms of optical scanning angles, were identical to those of the Au reflector. These results open up the possibility of increasing the laser power beyond 2W for LIDAR applications or other applications requiring high optical power. Finally, a packaged 2D scanner was integrated into a LIDAR system and three-dimensional point cloud images were obtained, demonstrating the scanning stability and operability of these 2D MEMS mirrors.