Meaningful Options Research Articles

‘Voluntary’ prison labour in the Netherlands

As of 2021, work in prisons in the Netherlands is voluntary, at least to some extent. In this article, I examine the protection of working prisoners’ labour rights after the shift to a voluntary work scheme for prisoners in the Netherlands. Work in Dutch prisons may be freely chosen to some extent, but the Dutch scheme for work in prison raises questions about offenders’ rehabilitation. Having work opportunities while in prison is said to contribute to the learning of skills, promote rehabilitation and societal reintegration and provide prisoners with income. However, prisoners in the Dutch prison perform their work for low pay and have limited meaningful options for the work they perform. This has a profound impact on their time in prison and on their reintegration into the labour market after having served their sentences. I argue that these issues demand an in-depth examination if prisoners’ rights are to be protected. I describe working prisoners’ labour rights in the Netherlands and address the normative question of the rights that working prisoners should have based on the principle that imprisonment itself is the punishment and that extensions of prison sentences in society are illegitimate. My proposal for considering the amendment of the approach to prison labour in the Netherlands aims to be useful for the analysis of prison labour in general.

Integrated post-acquisition data processing strategy for rapid steroid sulfate characterization in Toad gall-bladder

LC–MS serves as a workhorse for chemical profile characterization of Chinese medicinal materials (CMMs) attributing to the ability of measuring fruitful MS/MS spectral information. However, it is laborious to extract the information belonging to the compounds-of-interest from the massive data matrixes even employing those well-defined post-acquisition data processing strategies. Here, efforts were devoted to propose an integrated strategy allowing rapid chemical homologs-focused data filtering through integrating the fit-for-purpose existing strategies, such as molecular weight imprinting (MWI), diagnostic fragment ion filtering (DFIF), neutral loss filtering (NLF), and isotope pattern filtering (IPF). Homologs-focused chemical characterization of a precious CMM namely Toad gall-bladder (Chinese name: Chandan) that is rich of diverse effective steroid sulfates, particularly bufogenin sulfates, bile acid sulfates and bilichol sulfates, was employed as a proof-of-concept. Recombinant human SULT2A1-catalyzed in vitro metabolism was undertaken to generate eight bufogenin sulfates to facilitate summarizing MS/MS spectral behaviors. After in-house data library construction and MS1 and MS2 spectral acquisition, data filtering was conducted as follows: 1) MWI and IPF was utilized in combination to capture deprotonated molecular ions and the 34S isotopic ions for the sulfates of those reported steroids; 2) m/z 79.9568 (SO3−·) and 96.9596 (HSO4−) were applied to DFIF; and 3) SO3 (79.9568 Da) served as the feature to achieve NLF. Those captured MS/MS information subsequently participated in tentatively structural annotation through applying those empirical mass fragmentation rules. As a result, 71 compounds including 7 bufogenin sulfates, 17 bile acid sulfates, 13 bilichol sulfates and a C-23 steroid sulfate were detected from Toad gall-bladder and thereof, 39 ones received plausible identities assignment. Above all, the steroid sulfates in Toad gall-bladder were profiled in depth, and more importantly, the proposed strategy should be a meaningful option for, but not limited to, submetabolome characterization in CMMs.

High-efficiency selective removal of U(VI) by phosphate-functionalized graphitic carbon nitride activated using guanidine phosphate

Given the efficient reaction of P-containing species with radionuclide U(VI), phosphate-modified carbon nitrides (GPCNs) were prepared with enhanced surface areas (16.9–102.0 m2/g) and abundant phosphate groups (15.8–9.1 at% of P) and applied to capture aquatic U(VI). GPCNs presented a fast equilibrium of 8 h, efficient capture capability (maximum 333.5 mg/g at pH 5.0 and T 278 K), excellent selectivity and favorable reusability. The enrichment of U(VI) from the artificial nuclide wastewater (101.5 mg/g) and seawater (89.3 mg/g) were evaluated. Spectroscopic studies proved that the formation of hydrogen uranite was dominant for the high-efficiency selective sorption of U(VI). Under the illumination of visible-light, GPCNs showed a ∼4.9-fold faster kinetics for the photocatalytic reduction of U(VI) than CNs. Moreover, the origin of the photocatalytic activity of GPCNs including the role of phosphate modification was also discussed in detail. This study provided a valuable reference for the facile preparation of porous phosphate-modified carbon nitrides as well as a meaningful option for the extraction of radionuclides from aqueous solutions.

Telemedicine and the standard of care: a call for a new approach?

Telemedicine, understood as the provision of health care by a health professional to a patient who is physically not in the same location as the health professional, has many actual and potential benefits. It also has some disadvantages though, including a higher risk of misdiagnosis or another unfavorable outcome of certain remotely-provided services. In principle, the regime of legal liability for medical malpractice is the same for telemedicine as for traditional physical care. The general outline of the standard of care, which includes respect for medical science, the patient's individuality and objective possibilities, is abstract and flexible enough to be used for remote care without the need for redefinition. The quality of health care should be evaluated on the basis of the whole scale of risks and benefits it brings to a particular patient, including accessibility and comfort. In general, it should be permissible to provide a medical service remotely on the condition that its overall quality is at least as good as its comparable physical alternative. In other words, certain decrease in quality of some aspects of remote care can be compensated by other advantages. In terms of public health, support for telemedicine may bring a great improvement in the access to health care, and thus help significantly the individual members of the population. From the individual perspective, respect for personal autonomy implies that a patient should have every right to opt for a remote service, provided that there exists a true choice between meaningful options which is made on the basis of full information. If telemedicine is to fulfill its potential without sacrificing the protection of patients and their rights, reasonable guidelines for remote services need to be defined for particular medical fields, and for specific procedures within them. Among other issues, these guidelines must address the question of when it is necessary to refer the patient to physical care.

Effectiveness of Pregabalin in Treatment of Burning Mouth Syndrome

Background and Objectives Burning mouth syndrome (BMS) is a chronic pain disorder involving a burning sensation of the oral cavity without any identifiable oral lesion. According to the recent studies, the pathogenesis of BMS is presumed to be caused by a neuropathic condition. Gabapentin and pregabalin have been used for various neuropathic pains, but pregabalin has several pharmacokinetic advantages over gabapentin. To our best knowledge, there are no recent studies reported on the administration of pregabalin in treating BMS in Korea. Therefore, in this study, we investigated the therapeutic effect of pregabalin in treating BMS.Subjects and Method We chose as candidates 33 patients diagnosed as BMS and took pregabalin for more than four weeks. Pregabalin was administered at 75 mg once a day for 2 to 4 weeks at first, and then the dose was modified depending on whether or not symptoms improved. Effectiveness of treatment was evaluated in the way that the patients subjectively answered whether or not symptoms were improved.Results A total of 21 (63.6%) out of 33 patients were responsive to the treatment. Among those, at the last follow-up, 8 patients (38.1%) showed slight improvement, and 13 patients (61.9%) showed mostly improvement or disappearance of symptoms. The average time interval from starting pregabalin to the first symptom improvement was 50.1 days, and most patients showed symptom improvement within 8 weeks.Conclusion This study concludes that pregabalin can be added as a meaningful option in the treatment of BMS. The additional double-blind clinical study should be followed to further prove the effectiveness of pregabalin.

Status of Women in Neurosurgery: Results from a National Survey in Italy

Gender inequity in surgery has increasingly been a matter of debate. Contributions of female neurosurgeons to academic medicine and societies are poorly highlighted. The aim of this study was to evaluate several aspects of the professional and work-life balance of female neurosurgeons in Italy. Data of the female neurosurgical population were extracted from a general 83-item questionnaire administered to a total of 3242 respondents. The survey was composed of multiple-choice questions investigating demographics, surgical training and practice, satisfaction, mentorship, discrimination, and harassment. A total of 98 female neurosurgeons were included. Most responders were married or cohabiting (49%). Thirty-nine (43%) were planning to have children, and 15 of them (44%) stated the reason they still didn't have any was because of professional constraints. Seventy (71%) women were neurosurgeons with an academic position (residents or academics) and 28 (29%) were full-time attendings. Most of the female neurosurgeons are satisfied with their work: sometimes (35%), often (20%), and always or almost always (20%). Most of them (45%) stated they are rarely victims of harassment, but 66% think that they are treated differently because they are women. A similar rate for a poor and fulfilling work-life balance (34% and 35%, respectively) was detected. The majority of participants (89%) had encountered a role model during their career, but in only 11% of cases was that person female. Even though the rate of satisfaction among female neurosurgeons in Italy is high, some of them experienced gender discrimination, including incidents of sexual harassment and microaggressions. Policies including job sharing paradigms, consistent and meaningful options for parental leave, mentorship programs, equal and fair remuneration for equal work, and zero tolerance for harassment should be encouraged.

Comparison of neoadjuvant regimens for resectable gastroesophageal junction cancer: a systematic review of randomized clinical trials across three decades.

The optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors. We performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches. We identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47-100% and the 3-year OS ranged 6-66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8-80.6%] to surgery alone (60.9%; 95% CI: 60.4-61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6-64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT. Preoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study.

Insights into enhanced elimination of U(VI) and Eu(III) by amidoxime-functionalized Ti3C2Tx MXenes

Although two-dimensional transition metal carbides and carbonitrides (MXenes) are becoming increasingly popular in contaminant remediation field, the preparation of MXene nanosheets that can efficiently eliminate the target pollutants still deserves in-depth investigation. Here we produced amidoxime Ti3C2Tx nanosheets (TC-AO), which were efficient radionuclide adsorbents with high stability and positive affinity, by introducing the amidoxime group into the Ti3C2Tx MXene surface through grafting by diazonium salt. The high stability and abundant functional groups of TC-AO were demonstrated by different characterization techniques such as scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analyzer (TGA), and X-ray photoelectron spectroscopy (XPS). Multiple factors affecting the radionuclide removal performance were explored, including reaction time, temperature, pH, ionic strength, anions and cations. The experimental results demonstrated that the radionuclide uptake by TC-AO was a heat-absorbing, spontaneous single-molecule chemisorption process and was consistent with the pseudo-secondary and Langmuir models. When pH < 6, the mechanism of uranium removal was inner complexation, and as the pH continued to increase, uranium removal shifted to outer complexation. Furthermore, the results certificated that TC-AO exhibited fast reaction kinetics (reaching equilibrium in about 20 min), excellent removal efficiency (279.57 mg U·g−1 and 73.99 mg Eu·g−1), outstanding selectivity and good stability. The studies showed that TC-AO had good stability and functionality, which was not only valuable for the design of MXene based adsorbents, but also provided a meaningful option for the extraction of radioactive pollutants from wastewater.

Dwarfs on the Shoulders of Giants: Bayesian Analysis With Informative Priors in Elite Sports Research and Decision Making.

While sample sizes in elite sports are necessarily small, so are the effects that may be relevant. This conundrum is complicated by an understandable reluctance of athletes to comply with extensive study requirements. In Bayesian analyses, pre-existing knowledge (e.g., from sub-elite trials) can be formally included to supplement scarce data. Moreover, some design specifics for small sample research extend to the extreme case of a single subject. This provides the basis for actionable feedback (e.g., about individual responses) thereby incentivising participation. As a proof-of-concept, we conducted a replicated cross-over trial on the effect of cold-water immersion (CWI) on sprint performance recovery in soccer players. Times for 30 m linear sprint and the initial 5 m section, respectively, were measured by light gates before and 24 h after induction of fatigue. Data were analysed by Bayesian and by standard frequentist methods. Informative priors are based on a published metaanalysis. Seven players completed the trial. Sprint performance was 4.156 ± 0.193 s for 30 m linear sprint and 0.978 ± 0.064 s for the initial 5 m section. CWI improved recovery of sprint time for the initial 5 m section (difference to control: −0.060 ± 0.060 s, p = 0.004) but not for the full 30 m sprint (0.002 ± 0.115 s, p = 0.959), with general agreement between Bayesian and frequentist interval estimates. On the individual level, relevant differences between analytical approaches were present for most players. Changes in the two performance measures are correlated (p = 0.009) with a fairly good reproducibility of individual response patterns. Bayesian analyses with informative priors may be a practicable and meaningful option particularly for very small samples and when the analytical aim is decision making (use / don't use in the specific setting) rather than generalizable inference.

Software-Defined Networking Meets Software-Defined Radio in Mobile ad hoc Networks: State of the Art and Future Directions

The aims of this survey article are to elaborate on cross-layer optimization, Software-Defined Networking (SDN) and Software-Defined Radio (SDR) as separate domains of wireless network design for which a unified view has not been adequately considered to date and present lessons learned, with a view towards the challenges associated with SDN-SDR interaction that would facilitate benefits in cross-layer optimization of mobile ad hoc networks (MANETs). We focus on MANETs because ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${i}$ </tex-math></inline-formula> ) they are still at the forefront of technology, and in some scenarios they are the only meaningful option for establishing communication; ( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ii</i> ) they expose the full potential and benefits of coexistence and interaction of SDN and SDR, in terms of optimizing key performance indicators. While SDN and SDR are mature technologies, their interaction and joint consideration have been largely overlooked. Current SDN approaches do not span the physical (PHY) and medium-access control (MAC) layers, but they rather concentrate on network-level routing and traffic flow optimization. As a result, PHY- and MAC-layer related parameters which notoriously affect key network performance metrics remain static or at best are adapted based on some heuristic or local approaches. On the other hand, the reach of SDR architectures is restricted to the PHY and MAC layers. We discuss the state of the art of cross-layer optimization, SDN and SDR, and current challenges associated with coexistence and interaction of SDN and SDR. Such an interaction would extend the span of SDN to PHY and MAC layers and lead to realizations of centralized approaches across all layers so as to control and optimize parameters, towards global network objectives. It would also create a bridge between centralized network control that is inherent in SDN and the distributed nature of MANETs, with the add-on features of flexible and fast PHY and MAC layer adaptation offered by SDR, for solid, autonomous and ultimately better network control implementations that span all layers, towards realizing and implementing the holy grail of real cross-layer optimization.

Do the distal femur and the proximal tibia have narrower aspect ratios in smaller knees? : A morphological analysis of osteoarthritic knees in the Japanese population using computed tomography

BackgroundWhether the distal femur and the proximal tibia have narrower aspect ratios in smaller knees has not been clarified. The purpose of this study was to confirm the dimensional characteristics of the distal femur and the proximal tibia using a novel method for consistently determining knee size. MethodsA total of 220 Japanese osteoarthritic knees (160 female and 60 male knees) were analyzed using computed tomography. The mediolateral (ML) and the anteroposterior (AP) dimensions of the distal femur (fML, fAP) and the proximal tibia (tML, tAP) were measured. The aspect ratios (ML/AP) of the distal femur (fML/fAP) and the proximal tibia (tML/tAP) were assessed against the product of AP × ML as a consistent determination of knee size. ResultsThe fML/fAP ratios positively correlated with knee size (fAP × fML) (r = 0.420, p < 0.001), only in the combined cohort, attributable to the narrower aspect ratios of female knees. No correlations were found between the tML/tAP ratios and knee size (tAP × tML) among females, males, nor all subjects (p = 0.299, 0.994, and 0.996, respectively). Aspect ratio correlations to knee size diverged between the three knee size indices, AP, ML, and AP × ML. ConclusionsAP × ML was the meaningful option for knee size indexing in our morphological analyses. The distal femur, but not the proximal tibia, was found to have a narrower aspect ratio in female knees in the Japanese population.

An integrative framework of innovative work behavior for employees in SMEs linking knowledge sharing, functional flexibility and psychological empowerment

PurposeThis study aims to propose a model based on knowledge sharing (KS) to explore that how functional flexibility (FF) and psychological empowerment (PE) plays a mediating role between KS and innovative work behavior (IWB) among employees of small and medium enterprises (SMEs).Design/methodology/approachCross-sectional plan was employed to investigate the hypothesized model. Survey instrument was used to collect data from 769 employees of SMEs through self-administered questionnaires. Furthermore, correlation and structural equation modeling approach was used for the analysis of collected data.FindingsThe findings revealed that KS has a significant positive relationship with IWB. Second, FF and PE fully mediate between KS and IWB.Originality/valueThis study offers empirical evidence how to flourish a mechanism of IWB among employees in SMEs. Furthermore, this study highlighted some facts that should be meaningful options for human resource managers to understand the nexus of KS, FF and PE for enhancing the IWB among workers in SMEs. Moreover, the study in hand provided significant implications for management by focusing on KS as a fundamental predictor for IWB via FF and PE.

How many patients with inflammatory rheumatic diseases have the technical prerequisites for video consultations and are also willing to use this to carry out visits by medical specialist visits?

HintergrundDie aktuell grassierende SARS-CoV-2-Pandemie und begrenzte Kapazitäten in der ambulanten rheumatologischen Versorgung werfen, auch angesichts der digitalen Revolution, Fragen nach möglichen Alternativen zu klinischen Visiten auf. Ob und inwieweit Patienten mit entzündlich rheumatischen Erkrankungen bereit und in der Lage sind, mit den neuen Medien wie etwa Videosprechstunden (VSS) umzugehen, ist unklar.MethodenMitten in der Pandemie wurden im Mai 2020 ambulante Patienten mit einem standardisierten Fragebogen systematisch befragt, um ihre Möglichkeiten und die Bereitschaft für die Teilnahme an VSS zu ermitteln. Der behandelnde Arzt gab an, ob er die Durchführung einer VSS für möglich und auch für sinnvoll hielt.ErgebnisseInsgesamt wurden 232 Patienten mit entzündlich rheumatischen Erkrankungen befragt (64,7 % weiblich, mittleres Alter 54,0 ± 15,2 Jahre), seropositive (n = 58) und seronegative (n = 51) rheumatoide Arthritis (RA), Spondyloarthritis (SpA) (n = 77) inklusive der axialen SpA (axSpA) und der Psoriasisarthritis (PsA) sowie Kollagenosen und Vaskulitiden (KoV) (n = 46). Die mittlere Krankheitsdauer betrug 5,5 ± 8,2 Jahre, bei 75 Patienten (32,3 %) handelte es sich um eine Erstdiagnose. Die mittlere Krankheitsaktivität (0–10, subjektive Patienteneinschätzung) lag bei 4,7 ± 2,5. Insgesamt wussten 176 Patienten grundsätzlich über die Möglichkeit der Durchführung von VSS Bescheid (75,9 %), und 166 sahen sich technisch in der Lage, daran teilzunehmen (71,6 %), aber nur 131 waren grundsätzlich auch bereit dazu (56,5 %). Die logistische Regressionsanalyse zeigte, dass die Bereitschaft zur Teilnahme an VSS mit zunehmendem Alter abnahm (β = 0,28, p = 0,01). Nach ärztlicher Einschätzung wurden VSS bei 161 Patienten aus technischen (69,4 %) und bei 127 aus medizinischen Gründen (54,7 %) prinzipiell für möglich gehalten. Die Durchführung von VSS im Rahmen der Versorgung wurde vom Arzt aber nur bei 76 Patienten (32,8 %) für sinnvoll gehalten.ZusammenfassungNicht alle Patienten können oder wollen an VSS teilnehmen, mit zunehmendem Alter nimmt die Bereitschaft dazu ab. Auch die ärztliche Einschätzung der Sinnhaftigkeit von VSS beschränkte sich auf etwa ein Drittel der befragten Patienten. Dies ist für zukünftige Planungen von VSS zu berücksichtigen.

PMD7 Budget Impact Analysis of Transcutaneous Afferent Patterned Stimulation Therapy for the Treatment of Essential Tremor in the United States

INTRODUCTION: Essential tremor (ET) is a chronic, progressive, and disabling neurological disease, managed with poorly tolerated, partially effective pharmacological treatments and, in some patients, costly surgical or non-reversible ablative procedures. Transcutaneous afferent patterned stimulation (TAPS), delivered by a novel personalized medical device, provides non-invasive, on-demand stimulation of the same key brain networks as the most effective surgery, deep brain stimulation, and has an extensive clinical program demonstrating its efficacy and safety in the treatment of ET. With TAPS device costs concentrated at treatment initiation, an economic analysis was conducted to assess the near-term budget impact of its introduction for the treatment of ET. A cost minimization model was developed to calculate the 3-year impact of introducing TAPS therapy for a healthcare plan cohort of 1,000,000 people. Prevalence of ET, as well as costs and incidence of surgical and non-reversible ablative procedures, were gathered from published literature. Acquisition costs and proportion of patients receiving pharmacological treatment options were sourced from Redbook and 24-month data from Truven databases. The economic impact of introducing TAPS was calculated based on an alternative scenario where 3% of patients from each treatment received TAPS therapy. Within the plan population, 2,992 patients were estimated to receive ET treatment. Introduction of TAPS therapy would have a 3-year budget impact of $62,126 (+0.25% compared with current costs; +$130,233 in the first year and approximately -$34,050 in subsequent years), or $20.56 per treated patient and $0.002 PMPM. Introduction of TAPS therapy for the treatment of ET had a modest budget impact in the near-term based on acquisition costs alone. TAPS therapy offers an additional, clinically meaningful option for the treatment of ET that is likely to be cost neutral or cost saving when pharmacological adverse event costs or surgical and procedure complication costs are considered.

Solid Swallow Examination During High Resolution Manometry and EGJ-Distensibility Help Identify Esophageal Outflow Obstruction in Non-obstructive Dysphagia

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment.

Effect of Gamete Cryopreservation on miRNA Expression and Embryonic Development

Background: Fertility preservation is a meaningful option to retain fertility due to the medical or social needs. Sperm or oocytes preservation is the most extensive way for personal fertility preservation. Although the cryopreservation of sperm is well-used while the oocyte cryopreservation technology is improving, the effects and embryonic development potential of gamete cryopreservation need further investigation. Methods: The miRNAs expression of cryopreserved gamete was detected using miRNA sequencing in human and mouse, differentially expressed miRNAs (DEmiRs) were identified by comparing their expression in frozen-thawed and fresh gamete. Function of DEmiRs were detected by GO enrichment analysis, and common DEmiRs were validated by qRT-PCR. The embryonic developmental potential of cryopreserved sperm or oocytes were estimated in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cases by retrospective cohort study. Results: 21 and 106 DEmiRs were detected in human and mouse frozen-thawed sperm compared with fresh group, respectively. miR-148b-3p and miR-30b-5p were validated that downregulation in both human and mouse frozen-thawed sperm, while miR-140-5p was upregulated, these 3 common DEmiRs were enriched in positive regulation of mitotic cell cycle, in utero embryonic development and others. Meanwhile, 285 DEmiRs were identified in mouse frozen-thawed oocytes, the number of DEmiRs was 2.61-fold than that in mouse sperm. The downregulation of miR-148b-3p and miR-30b-5p were also validated in mouse frozen-thawed oocytes. Clinic data of embryonic development which used cryopreserved sperm indicated the significant decrease of fertilization rete in both IVF and ICSI cases, as well as the decrease of blastocyst formation rate in ICSI cases, while the significant decrease of high qualified embryo rate was observed when used the cryopreserved oocytes compared with paired fresh oocytes which retrieved from the same female in ICSI cases, suggesting the potential negative effects of gamete cryopreservation on embryonic development. Conclusion: Cryopreservation could change the expression of miRNAs in both sperm and oocyte, and the altered miRNAs expression pattern further affected the fertilization and development of embryo. Funding Statement: This research was funded by National Key R&D Program of China (2017YFC1001300). The National Natural Science Foundation of China (81771651, 81873832). The Research Projects of Shanghai Science and Technology Commission (18411964300). Declaration of Interests: The authors declare there are no competing interests. Ethics Approval Statement: The animal experimental procedures were approved by the Institutional Animal Care and Use Committee of Tongji University and the Ethics Committee of the Institute of Animal Science, Tongji University (TJAA06420101). Human sperm samples were donated for research from patients who had provided informed consent at Tongji hospital, with the approval of the Institutional Ethical Committee for Scientific Research (2019-062).

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program.

Introduction:We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.Patients and Methods:Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed.Results:In total, 52 patients were included [median age 57 years (range 32–81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively. G1202R and G2032R resistance mutations prior to treatment with lorlatinib were observed in 10 of 26 evaluable patients (39%), 11 of 39 patients showed TP53 mutations (28%). Thirty-six patients (69%) had active brain metastases (BM) and nine (17%) leptomeningeal carcinomatosis when entering the EAP. Median number of prior specific TKIs was 3 (range 1–4). Median duration of treatment, progression-free survival (PFS), response rate and time to treatment failure were 10.4 months, 8.0 months, 54% and 13.0 months. Calculated 12-, 18- and 24-months survival rates were 65, 54 and 47%, overall survival since primary diagnosis (OS2) reached 79.6 months. TP53 mutations were associated with a substantially reduced PFS (3.7 versus 10.8 month, HR 3.3, p = 0.003) and were also identified as a strong prognostic biomarker (HR for OS2 3.0 p = 0.02). Neither prior treatments with second-generation TKIs nor BM had a significant influence on PFS and OS.Conclusions:Our data from real-life practice demonstrate the efficacy of lorlatinib in mostly heavily pretreated patients, providing a clinically meaningful option for patients with resistance mutations not covered by other targeted therapies and those with BM or leptomeningeal carcinomatosis.

Older Adult Cohousing Communities: The Lived Experience

“We’re on the leading edge of the baby boomers so we don’t do anything like anybody has ever done before and that includes aging.” (Tammy, SS). This quote embodies the perspective of older adults engaged in a new housing phenomenon – older adult cohousing communities (OACCs). OACCs are designed, managed, governed and maintained by the older residents themselves. Seventeen such communities currently exist, and more are being developed by active baby boomers who are searching for more meaningful, relational and eco-friendly options for aging-in-place. The older adult cohousing movement in the U.S., which began in 2005, is small but growing quickly. However, a dearth of literature exists on this phenomenon. This qualitative study examined older adult cohousers’ lived experiences. The study employed an existential-phenomenological research method. Maximum variation purposive sampling was employed. Twelve communities were identified that represented the full range of geographic environments, structures, missions, cost and size. Interviews were conducted individually or in focus groups. In all, 73 older adult cohousers participated in the study. The Gerotranscendence Theory of Aging was used to guide the development of the structured interview questions and to organize data analysis and interpretation. Digital recordings were transcribed, and an inductive method was used to allow codes and themes to arise from the data itself. Patton’s (1990) criteria for judging themes was employed. This poster will clarify the nature, principles and structure of OACCs. Themes that emerged from the study - benefits, challenges, aging-in-place, interpersonal relationships and personal growth - will be described .

The Limits of Rehabilitation and Recidivism Reduction: Rethinking the Evaluation of Arts Programming in Prisons

Canadian prison-based arts and other programming are limited at best. Even the country’s Correctional Investigator, or prison-ombudsperson, has critiqued the lack of meaningful options in which prisoners can engage. Those programs that do exist tend to be focused on the logic of penal rehabilitation, with the end goal of reducing recidivism. In this article, we showcase the evaluation of a 9-week arts program in a women’s prison, the aim of which was to build community and foster artistic engagement, thus running counter to normative carceral logics.

Fighting excessive pharmaceutical prices: Evaluating the options

Abstract Background New treatment options for various cancer therapies have appeared extremely expensive and prices may increase further. The affordability and availability of life-saving medicines is therefore a key issue in national health policies of all countries. Fighting excessive pharmaceutical prices, this paper examined a 'toolbox' of price reducing measures, provided by international law (e.g., compulsory licensing, pharmacy's exemption, price transparency and mandatory disclosure, competition authorities' review unfair prices, crossborder purchasing medicines). Results Evaluating the options, states remain hesitant, if not reluctant to apply for compulsory licensing and or other regulatory options to curtail pharmaceutical prices. Instead, Cross-border collaboration on (price and cost) negotiation of selective medicines seems the most feasible remedy to create advantages of economies of scale, and thus providing access to affordable new medicines. Conclusions Despite some obstacles, voluntary cross-border purchasing arrangements are a meaningful option to safeguard access to affordable innovative medicines, particularly for small countries Methods Legal analysis treaty law, provisions, case law, and literature. Key messages Voluntary cross-border purchasing arrangements are a meaningful option to safeguard access to affordable innovative medicines. Particularly for small countries.