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Multiple studies have demonstrated that cancer cells with microsatellite instability (MSI) are intolerant to loss of the Werner syndrome helicase (WRN), whereas microsatellite-stable (MSS) cancer cells are not. Therefore, WRN represents a promising new synthetic lethal target for developing drugs to treat cancers with MSI. Given the uncertainty of how effective inhibitors of WRN activity will prove in clinical trials, and the likelihood of tumours developing resistance to WRN inhibitors, alternative strategies for impeding WRN function are needed. Proteolysis-targeting chimeras (PROTACs) are heterobifunctional small molecules that target specific proteins for degradation. Here, we engineered the WRN locus so that the gene product is fused to a bromodomain (Bd)-tag, enabling conditional WRN degradation with the AGB-1 PROTAC specific for the Bd-tag. Our data revealed that WRN degradation is highly toxic in MSI but not MSS cell lines. In MSI cells, WRN degradation caused G2/M arrest, chromosome breakage and ATM kinase activation. We also describe a multi-colour cell-based platform for facile testing of selective toxicity in MSI versus MSS cell lines. Together, our data show that a degrader approach is a potentially powerful way of targeting WRN in MSI cancers and paves the way for the development of WRN-specific PROTAC compounds. [ABSTRACT FROM AUTHOR]

The electrochemical carbon dioxide reduction reaction (CO2RR) is a promising approach for reducing atmospheric carbon dioxide (CO2) emissions, allowing harmful CO2 to be converted into more valuable carbon‐based products. On one hand, single carbon (C1) products have been obtained with high efficiency and show great promise for industrial CO2 capture. However, multi‐carbon (C2+) products possess high market value and have demonstrated significant promise as potential products for CO2RR. Due to CO2RR's multiple pathways with similar equilibrium potentials, the extended reaction mechanisms necessary to form C2+ products continue to reduce the overall selectivity of CO2‐to‐C2+ electroconversion. Meanwhile, CO2RR as a whole faces many challenges relating to system optimization, owing to an intolerance for low surface pH, systemic stability and utilization issues, and a competing side reaction in the form of the H2 evolution reaction (HER). Ethylene (C2H4) remains incredibly valuable within the chemical industry; however, the current established method for producing ethylene (steam cracking) contributes to the emission of CO2 into the atmosphere. Thus, strategies to significantly increase the efficiency of this technology are essential. This review will discuss the vital factors influencing CO2RR in forming C2H4 products and summarize the recent advancements in ethylene electrosynthesis. [ABSTRACT FROM AUTHOR]

Introduction: Chatbot Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence-powered language model chatbot able to help otolaryngologists in practice and research. The ability of ChatGPT in generating patient-centered information related to laryngopharyngeal reflux disease (LPRD) was evaluated. Methods: Twenty-five questions dedicated to definition, clinical presentation, diagnosis, and treatment of LPRD were developed from the Dubai definition and management of LPRD consensus and recent reviews. Questions about the four aforementioned categories were entered into ChatGPT-4. Four board-certified laryngologists evaluated the accuracy of ChatGPT-4 with a 5-point Likert scale. Interrater reliability was evaluated. Results: The mean scores (SD) of ChatGPT-4 answers for definition, clinical presentation, additional examination, and treatments were 4.13 (0.52), 4.50 (0.72), 3.75 (0.61), and 4.18 (0.47), respectively. Experts reported high interrater reliability for sub-scores (ICC = 0.973). The lowest performances of ChatGPT-4 were on answers about the most prevalent LPR signs, the most reliable objective tool for the diagnosis (hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH)), and the criteria for the diagnosis of LPR using HEMII-pH. Conclusion: ChatGPT-4 may provide adequate information on the definition of LPR, differences compared to GERD (gastroesophageal reflux disease), and clinical presentation. Information provided upon extra-laryngeal manifestations and HEMII-pH may need further optimization. Regarding the recent trends identifying increasing patient use of internet sources for self-education, the findings of the present study may help draw attention to ChatGPT-4's accuracy on the topic of LPR. [ABSTRACT FROM AUTHOR]

Irish Catholic primary education operates within a context increasingly marked by detraditionalisation and secularisation. As religious belief and identity recedes in Ireland, Catholic schools face challenges in enabling the children they serve to develop a personal relationship with God and nurturing their faith formation and development, an important element of the mission of the Catholic school. At the same time, mindfulness practice has grown exponentially in popularity across many sectors of society, including in Irish education. A growing body of research supports mindfulness practice in schools, citing benefits such as improved academic performance and enhanced wellbeing. This review examines the development of mindfulness practice in Irish Catholic primary schools. Curricular reform in primary education regarding the growing role of wellbeing is explored. The review also addresses opportunities and challenges to mindfulness practice in these schools. [ABSTRACT FROM AUTHOR]

This article contends that James Baldwin's exploration of racism and resistance to it in The Fire Next Time may be put into conversation with Ludwig Wittgenstein's consideration of fundamental epistemic commitments in On Certainty. Out of this constructive engagement, I argue that white supremacism in the United States may be interpreted as being like a Wittgensteinian grounding or "hinge" commitment and that this viewpoint illuminates some of the ways in which white supremacism may interact with various kinds of religious commitments. This combined analysis depicts, first, the extent to which fundamental commitments about race deeply affect people, including the formation of their ethical and civic values, existential and religious commitments, and range of empathetic capacity and, second, similarities between Baldwin and Wittgenstein when it comes to their contentions that there is ethical value in the clarification of language and work on oneself. [ABSTRACT FROM AUTHOR]

A reservoir computer is a type of dynamical system arranged to do computation. Typically, a reservoir computer is constructed by connecting a large number of nonlinear nodes in a network that includes recurrent connections. In order to achieve accurate results, the reservoir usually contains hundreds to thousands of nodes. This high dimensionality makes it difficult to analyze the reservoir computer using tools from the dynamical systems theory. Additionally, the need to create and connect large numbers of nonlinear nodes makes it difficult to design and build analog reservoir computers that can be faster and consume less power than digital reservoir computers. We demonstrate here that a reservoir computer may be divided into two parts: a small set of nonlinear nodes (the reservoir) and a separate set of time-shifted reservoir output signals. The time-shifted output signals serve to increase the rank and memory of the reservoir computer, and the set of nonlinear nodes may create an embedding of the input dynamical system. We use this time-shifting technique to obtain excellent performance from an opto-electronic delay-based reservoir computer with only a small number of virtual nodes. Because only a few nonlinear nodes are required, construction of a reservoir computer becomes much easier, and delay-based reservoir computers can operate at much higher speeds. [ABSTRACT FROM AUTHOR]

Objective: To study the management of laryngopharyngeal reflux (LPR) among the subspecialties of practicing otolaryngology-head and neck surgeons and their trainees. Methods: A survey was sent to over 8000 otolaryngologists (OTOHNS) over 65 countries, utilizing membership lists of participating otolaryngological societies. The outcomes were answers to questions regarding LPR knowledge and practice patterns, and included queries about its definition, prevalence, clinical presentation, diagnosis, and treatment. Results: Of the 824 respondents, 658 practiced in one specific otolaryngologic subspecialty. The symptoms and findings thought to be the most related to LPR varied significantly between subspecialists. Extra-laryngeal findings were considered less by laryngologists while more experienced OTOHNS did not often consider digestive complaints. Compared with colleagues, otologists, rhinologists and laryngologists were less aware of the involvement of LPR in otological, rhinological and laryngological disorders, respectively. Irrespective of subspecialty, OTOHNS consider symptoms and signs and a positive response to empirical therapeutic trial to establish a LPR diagnosis. Awareness regarding the usefulness of impedance pH-studies is low in all groups. The therapeutic approach significantly varies between groups, although all were in agreement for the treatment duration. The management of non-responder patients demonstrated significant differences among laryngologists who performed additional examinations. The majority of participants (37.1%) admitted to being less than knowledgeable about LPR management. Conclusions: LPR knowledge and management vary significantly across otolaryngology subspecialties. International guidelines on LPR management appear necessary to improve knowledge and management of LPR across all subspecialties of otolaryngology. [ABSTRACT FROM AUTHOR]

Background: We used a quality improvement framework to transform two-day and in-person advanced communication training (ACT) course into a remote ACT (Re-ACT) format to help clinicians improve serious illness conversation (SIC) skills.Measures: We assessed the reach, impact, and costs of Re-ACT and compared these measures to in-person ACT courses.Interventions: About 45-60 minutes of synchronous, remote sessions consisting of a didactic introduction to SIC skills, tailored to the SARS-Cov-2 (COVID-19) crisis, and a live demonstration of SICs with patient-actors.Outcomes: The transition to Re-ACT sessions resulted in reaching a greater number of clinicians in less time, although depth of content and opportunities for skill practice decreased. Although both formats were well received, Re-ACT respondents felt less prepared than ACT respondents to use SIC skills. The costs of Re-ACT were significantly less than in-person ACT courses.Conclusions/lessons Learned: We provided effective and well-received SIC training during a time of crisis. Future work should further define the optimal mix of in-person and remote experiences to teach SIC skills. [ABSTRACT FROM AUTHOR]

Carbon 1s photoelectron spectra for 2-butyne (CH3C≡CCH3) measured in the photon energy range from threshold to 150 eV above threshold show oscillations in the intensity ratio C2,3/C1,4. Similar oscillations have been seen in chloroethanes, where the effect has been attributed to EXAFS-type scattering from the substituent chlorine atoms. In 2-butyne, however, there is no high-Z atom to provide a scattering center and, hence, oscillations of the magnitude observed are surprising. The results have been analyzed in terms of two different theoretical models: a density-functional model with B-spline atom-centered functions to represent the continuum electrons and a multiple-scattering model using muffin-tin potentials to represent the scattering centers. Both methods give a reasonable description of the energy dependence of the intensity ratios. [ABSTRACT FROM AUTHOR]

N6-methyladenosine is the most prominent RNA modification in mammals. Here, we study mouse skin embryogenesis to tackle m6A's functions and physiological importance. We first landscape the m6A modifications on skin epithelial progenitor mRNAs. Contrasting with in vivo ribosomal profiling, we unearth a correlation between m6A modification in coding sequences and enhanced translation, particularly of key morphogenetic signaling pathways. Tapping physiological relevance, we show that m6A loss profoundly alters these cues and perturbs cellular fate choices and tissue architecture in all skin lineages. By single-cell transcriptomics and bioinformatics, both signaling and canonical translation pathways show significant downregulation after m6A loss. Interestingly, however, many highly m6A-modified mRNAs are markedly upregulated upon m6A loss, and they encode RNA-methylation, RNA-processing and RNA-metabolism factors. Together, our findings suggest that m6A functions to enhance translation of key morphogenetic regulators, while also destabilizing sentinel mRNAs that are primed to activate rescue pathways when m6A levels drop. [ABSTRACT FROM AUTHOR]

The article explores the different forms of reticence in philosophical and ethical discourses in Confucius' "Analects" and the philosophy of Austrian-British philosopher Ludwig Wittgenstein. Topics covered include the explicit and implicit discussion of reticence in the "Analects" and the various forms of reticence in the "Analects" and in the philosophy of Wittgenstein.

Comparative transcriptomics between differentiating human pluripotent stem cells (hPSCs) and developing mouse neurons offers a powerful approach to compare genetic and epigenetic pathways in human and mouse neurons. To analyze human Purkinje cell (PC) differentiation, we optimized a protocol to generate human pluripotent stem cell-derived Purkinje cells (hPSC-PCs) that formed synapses when cultured with mouse cerebellar glia and granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. To directly compare global gene expression of hPSC-PCs with developing mouse PCs, we used translating ribosomal affinity purification (TRAP). As a first step, we used Tg(Pcp2-L10a-Egfp) TRAP mice to profile actively transcribed genes in developing postnatal mouse PCs and used metagene projection to identify the most salient patterns of PC gene expression over time. We then created a transgenic Pcp2- L10a-Egfp TRAP hPSC line to profile gene expression in differentiating hPSC-PCs, finding that the key gene expression pathways of differentiated hPSC-PCs most closely matched those of late juvenile mouse PCs (P21). Comparative bioinformatics identified classical PC gene signatures as well as novel mitochondrial and autophagy gene pathways during the differentiation of both mouse and human PCs. In addition, we identified genes expressed in hPSC-PCs but not mouse PCs and confirmed protein expression of a novel human PC gene, CD40LG, expressed in both hPSC-PCs and native human cerebellar tissue. This study therefore provides a direct comparison of hPSC-PC and mouse PC gene expression and a robust method for generating differentiated hPSC-PCs with human-specific gene expression for modeling developmental and degenerative cerebellar disorders. [ABSTRACT FROM AUTHOR]

Carbon 1s photoelectron spectra for CF[sub 4] and CO have been measured at several photon energies near the carbon 1s threshold. The spectra have been analyzed in terms of the vibrational structure and the natural linewidth. For CO the vibrational structure shows evidence for anharmonicity in both the energy spacing and the intensity. Analysis of the results using an anharmonic model gives an equilibrium bond length for core-ionized CO that is 4.85 pm shorter than that of neutral CO. For CF[sub 4], the vibrational structure is very weak, and the analysis shows that the change in equilibrium CF bond length upon ionization is no more than 0.54 pm. Ab initio theoretical calculations give results in accord with these bond-length changes. The unusually small bond-length contraction in CF[sub 4] can be understood in terms of nonbonded fluorine—fluorine repulsion. The natural linewidth for core-ionized CO, 95 ± 5 meV, is essentially the same as that of CH[sub 4]. This result is in contrast with expectations based on the one-center model of Auger decay and earlier predictions based on semiempirical molecular orbital theory. More recent calculations indicate, however, that there is only a small difference between CO and CH[sub 4], in agreement with the observed result. For CF[sub 4], the natural linewidth is 77±6 meV. This value differs from that for CH[sub 4] in the direction expected from the electronegativities of hydrogen and fluorine, but is greater than the prediction based on semiempirical theory. The natural linewidth for CO with a carbon 1s electron excited to the 2π resonance is 83 meV, which is significantly less than is found for core-ionized CO. Although this difference is supported by theoretical calculations, the direction of the difference is counterintuitive. An overview is presented of the current state of experimental and theoretical knowledge on carbon 1s linewidths. [ABSTRACT FROM AUTHOR]

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage–specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type–specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell–progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages. [ABSTRACT FROM AUTHOR]

During late mitosis and the early G1 phase, the origins of replication are licensed by binding to double hexamers of MCM2-7. In this study, we investigated how licensing and proliferative commitment are coupled in the epithelium of the small intestine. We developed a method for identifying cells in intact tissue containing DNA-bound MCM2-7. Interphase cells above the transit-amplifying compartment had no DNA-bound MCM2-7, but still expressed the MCM2-7 protein, suggesting that licensing is inhibited immediately upon differentiation. Strikingly, we found most proliferative Lgr5+ stem cells are in an unlicensed state. This suggests that the elongated cell-cycle of intestinal stem cells is caused by an increased G1 length, characterized by dormant periods with unlicensed origins. Significantly, the unlicensed state is lost in Apc-mutant epithelium, which lacks a functional restriction point, causing licensing immediately upon G1 entry. We propose that the unlicensed G1 phase of intestinal stem cells creates a temporal window when proliferative fate decisions can be made. [ABSTRACT FROM AUTHOR]

Objectives: Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. Methods: Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. Results: Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 (P < .05), for a delta VHI-10 of 8.3, or 30.9% improvement. Twelve of the 15 (80%) showed a clinically significant improvement (delta VHI-10 >5). Conclusions: A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation. [ABSTRACT FROM AUTHOR]

For inoperable esophageal adenocarcinoma (EAC), identifying patients likely to benefit from recently approved immunochemotherapy (ICI+CTX) treatments remains a key challenge. We address this using a uniquely designed window-of-opportunity trial (LUD2015-005), in which 35 inoperable EAC patients received first-line immune checkpoint inhibitors for four weeks (ICI-4W), followed by ICI+CTX. Comprehensive biomarker profiling, including generation of a 65,000-cell single-cell RNA-sequencing atlas of esophageal cancer, as well as multi-timepoint transcriptomic profiling of EAC during ICI-4W, reveals a novel T cell inflammation signature (INCITE) whose upregulation correlates with ICI-induced tumor shrinkage. Deconvolution of pre-treatment gastro-esophageal cancer transcriptomes using our single-cell atlas identifies high tumor monocyte content (TMC) as an unexpected ICI+CTX-specific predictor of greater overall survival (OS) in LUD2015-005 patients and of ICI response in prevalent gastric cancer subtypes from independent cohorts. Tumor mutational burden is an additional independent and additive predictor of LUD2015-005 OS. TMC can improve patient selection for emerging ICI+CTX therapies in gastro-esophageal cancer. [Display omitted] • An EAC immunochemotherapy (ICI+CTX) trial: four weeks of ICI (ICI-4W), then ICI+CTX • A T/NK cell gene signature (INCITE) is upregulated in patients responding to ICI • High tumor monocyte content and mutational burden predict ICI+CTX outcomes • This biomarker combination also shows promise for EBV-/MSS gastric cancer Carroll et al. report that four weeks of immune checkpoint inhibitors is sufficient to induce tumor shrinkage in esophageal adenocarcinoma patients upregulating the "INCITE" gene signature. Integration of single-cell RNA sequencing and bulk RNA sequencing through deconvolution identified tumor monocyte content and tumor mutational burden as independent and complementary predictive biomarkers for immunochemotherapy. [ABSTRACT FROM AUTHOR]

Background: First tarsometatarsal joint arthrodesis is a common procedure performed by podiatrists and orthopedic surgeons. There remains debate on how useful CT scans are in assessing fusion status in the post-operative patient. The purpose of our study was to determine the reliability among both orthopedic surgeons and radiologists in reviewing both postoperative radiographs and CT in order to determine if fusion had occurred in patients undergoing 1st tarsometatarsal arthrodesis. A secondary purpose of this study was to determine if CT offered improved inter- and intra-rater reliability when compared to plain radiographs. Methods: Patients who underwent 1st tarsometatarsal arthrodesis were retrospectively reviewed and those who underwent CT post-operatively for persistent pain were identified. Orthopedic surgeons and radiologists then analyzed the radiographs and CT of these patients for union with a threshold for union being set at 50% of the joint being fused. Imaging was then re-evaluated by the same provider 6 months later. Results: 24 patients were identified meeting inclusion criteria. Inter-rater reliability and intra-rater reliability for assessment of 1st tarsometatarsal arthrodesis were better with CT compared to radiographs; however, this association was not deemed reliable. Both imaging modalities were not able to assess union status confidently and reliably across reviewers, although CT scan had better intra-rater reliability. Conclusions: While CT is frequently used to assess fusion in patients who have underwent 1st tarsometatarsal arthrodesis, it was not found to be better than radiographs. Practitioners should reconsider the use CT as the gold standard when assessing fusion in this population. [ABSTRACT FROM AUTHOR]

Homeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particularly important in the intestinal epithelium where lineage tracing suggests that stochastic differentiation choices are intricately coupled to the position of a cell relative to a niche. To determine how position is achieved, we followed proliferating cells in intestinal organoids and discovered that the behaviour of mitotic sisters predicted long-term positioning. We found that, normally, 70%of sisters remainneighbours, while 30%losecontact and separate after cytokinesis. These post-mitotic placements predict longer term differences in positions assumed by sisters: adjacent sisters reach similar positions over time; in a pair of separating sisters, one remains close to its birthplace while the other is displaced upward. Computationally modelling crypt dynamics confirmed that post-mitotic separation leads to sisters reaching different compartments. We show that interkinetic nuclear migration, cell size and asymmetric tethering by a process extending from the basal side of cells contribute to separations. These processes are altered in adenomatous polyposis coli (Apc) mutant epithelia where separation is lost. We conclude that post-mitotic placement contributes to stochastic niche exit and, when defective, supports the clonal expansion of Apc mutant cells. [ABSTRACT FROM AUTHOR]

Outcomes: 1. Discuss the Palliative Care Education Curriculum (PCEC)—a collaboration between training programs and palliative care educators to customize primary palliative care (PPC) education to each training program's needs 2. Describe the PCEC Toolbox—a suite of tools including surveys and didactics that is easily adapted to the specific PPC educational needs of any training program All clinicians need basic palliative care (PC) skills to provide optimal patient care. The skills and knowledge that should be provided by non-PC specialists is commonly termed "primary palliative care " (PPC) and is distinct from "specialist PC," which includes more complex interventions provided by a specialty trained clinician. The goals of the Palliative Care Education Curriculum (PCEC) are threefold: 1) to design a suite of tools that PC educators can quickly and easily adapt to the specific PC educational needs of any training program, 2) to evaluate the PPC educational needs of individual training programs and create customized PCEC programs that regularly adjust to the input of the trainees and faculty, and 3) to create and foster a community of educators interested in improving PPC education within their specialty. During this concurrent session, we will first describe the PCEC Toolbox, which includes a needs assessment for initial and ongoing evaluation, adaptable didactics, and administrative infrastructure to keep the PCEC running smoothly. Second, we will review our experience with custom-made PCEC programs for seven unique training programs (Internal Medicine, Med-Peds, Urology, Critical Care, Physical Medicine & Rehab, Critical Care, Geriatrics, and Heart Failure) within one academic medical center and discuss our methods to guide targeted, incremental, programmatic adjustment. Third, we will discuss how PCEC is used to foster a community of educators interested in optimizing PPC skills and knowledge within their specialty. Finally, we will review data from 2 years of the PCEC program, discuss lessons learned, and consider the future of the current PCEC programs. We will also provide suggestions for adapting this model to participants' own institutions to expand PPC education more broadly. [ABSTRACT FROM AUTHOR]

The article compares the Confucian rectification of names, as represented by Roger Ames and Chad Hansen, and Wittgenstein's philosophical pursuit of clarity, arguing that the two may help shed light on each other. It reports the ethics of clarification presents difference between the two lies in perspicuity operating as an ultimate end for Wittgenstein, while for Confucianism rectification of names itself serves the ultimate end of renewal of social harmony.

Objectives: Prior studies demonstrate inconsistent diagnostic strategies for laryngopharyngeal reflux disease (LPR) patients who are offered laparoscopic Nissen fundoplication (Nissen). Superior symptom resolution outcomes are demonstrated in patients with accompanying typical gastroesophageal reflux (GERD) symptoms. This study aims to evaluate the efficacy of selecting patients with LPR complaints for Nissen using full column, dual pH impedance catheters (multichannel intraluminal impedance catheters [MII]). Methods: All patients who underwent Nissen for management of LPR symptoms refractory to at least 3 months of twice daily (BID) proton pump inhibitor (PPI) therapy with reflux symptom index (RSI) of 13 or higher and who had demonstrable reflux on MII were included. Pre- and (minimum) 16 week post-Nissen RSI scores as well as LPR-specific complaints were collected. Results: Eleven patients met criteria. Nine subjects (5 female, 4 male) had complete data. All 9 (100%) achieved improvement in RSI. The average pre-Nissen RSI was 31.7, and average post-Nissen RSI was 10 (P < .001). Six (67%) subjects dropped below an RSI of 13. Seven subjects (78%) had resolution of their primary LPR symptom, and 6 (67%) subjects had resolution of all LPR symptoms. Conclusions: Patients with LPR who are selected using dual pH and full column impedance are likely to demonstrate improvement in RSI following Nissen. [ABSTRACT FROM AUTHOR]

Planar cell polarity (PCP) or tissue polarity refers to the polarization of tissues perpendicular to the apical-basal axis. Most epithelia, including the vertebrate kidney, show signs of planar polarity. In the kidney, defects in planar polarity are attributed to several disease states including multiple forms of cystic kidney disease. Indeed, planar cell polarity has been shown to be essential for several cellular processes that appear to be necessary for establishing and maintaining tubule diameter. However, uncovering the genetic mechanisms underlying PCP in the kidney has been complicated as the roles of many of the main players are not conserved in flies and vice versa. Here, we review a number of cellular and molecular processes that can affect PCP of the kidney with a particular emphasis on the mechanisms that do not appear to be conserved in flies or that are not part of canonical determinants. [ABSTRACT FROM AUTHOR]

An increasing number of individuals are being recruited to whole genome sequencing (WGS) research. When asked hypothetically, the majority of the public express willingness to participate in this type of research, yet little is known about how many individuals will actually consent to research participation or what they perceive the risks to be. The MedSeq Project is a clinical trial exploring WGS in clinical care. We documented primary reason(s) for declining participation and reviewed audio-recorded informed consent sessions to identify participants’ concerns. Of 514 individuals recruited, 173 (34%) actively declined, 205 (40%) enrolled, and the remaining 136 (26%) were ineligible, unresponsive or waitlisted. Although the majority of active decliners cited logistical barriers, 40% cited risks related to the ethical, legal, and social implications (ELSI) of WGS research. Participants similarly discussed ELSI-related concerns but felt the potential benefits of participation outweighed the risks. Findings provide insight into the perspectives of potential WGS research participants and identify potential barriers to participation. [ABSTRACT FROM AUTHOR]

Despite the growth in research in philosophy of religion over the past several decades, recent years have seen a number of critical studies of this subfield in an effort to redirect the methods and topics of inquiry. This article argues that in addition to problems of religious parochialism described by critics such as Wesley Wildman, the subfield is facing a problem of relevance. In responding to this problem, it suggests that philosophers of religion should do three things: first, be critically self-aware about their aims of inquiry; second, investigate concepts used by other philosophers, scientists, and religious studies scholars to identify and dispel confusion about religions; and third, following the model of applied ethics, work to clarify concepts and advance arguments of contemporary practical urgency. [ABSTRACT FROM AUTHOR]

We review some of the history and early work in the area of synchronization in chaotic systems. We start with our own discovery of the phenomenon, but go on to establish the historical timeline of this topic back to the earliest known paper. The topic of synchronization of chaotic systems has always been intriguing, since chaotic systems are known to resist synchronization because of their positive Lyapunov exponents. The convergence of the two systems to identical trajectories is a surprise. We show how people originally thought about this process and how the concept of synchronization changed over the years to a more geometric view using synchronization manifolds. We also show that building synchronizing systems leads naturally to engineering more complex systems whose constituents are chaotic, but which can be tuned to output various chaotic signals. We finally end up at a topic that is still in very active exploration today and that is synchronization of dynamical systems in networks of oscillators. [ABSTRACT FROM AUTHOR]

Background: The relevance of the Simpson grading system as a predictor of meningioma progression or recurrence in modern neurosurgical practice has recently been called into question. The aim of our study was to compare the risk of progression/recurrence of tumours that had been treated with different Simpson grade resections in a contemporary population of benign (WHO grade I) meningioma patients. Method: One hundred eighty-three patients with histologically confirmed WHO grade I meningioma were retrospectively analysed. All patients underwent first-time craniotomy as their initial therapy between 2004 and 2012. Univariate analysis was performed using log-rank testing and Kaplan-Meier analysis for progression/recurrence-free survival. Multivariate analysis was performed using Cox proportional hazards regression modelling. Results: The three-year progression/recurrence-free survival rates for patients receiving Simpson grade 1, 2 or 4 resections were 95 %, 87 % and 67 %, respectively. Simpson grade 4 resections progressed/recurred at a significantly greater rate than Simpson grade 1 resections (hazard ratio [HR] = 3.26, P = 0.04), whereas Simpson grade 2 resections did not progress/recur at a significantly greater rate than Simpson grade 1 resections (HR = 1.78, P = 0.29). Subtotal resections progressed/recurred at a significantly greater rate than gross-total resections (HR = 2.47, P = 0.03). Conclusions: Tumours that undergo subtotal resection are at a significantly greater risk of progression/recurrence than tumours that undergo gross-total resection. Gross-total resection should therefore be the aim of surgery. However, given modern access to follow-up imaging and stereotactic radiosurgery, these results should not be used to justify overly 'heroic' tumour resection. [ABSTRACT FROM AUTHOR]