Stability Of Patterns Research Articles

Aeroelastic wind tunnel investigations on rectangular-planed air-supported membrane structures

This study implements aeroelastic wind tunnel experiments on rectangular-planed air-supported membrane structures. With the goal of identifying possible wind response patterns, experiments are conducted with a wide range of wind velocities, internal pressures, and membrane tensile stiffness, including cases close to similarity requirements for simulating prototypes. Wind pressure measurements on the rigid model are performed to serve as a reference, and during subsequent aeroelastic wind tunnel tests, time-averaged and fluctuating wind responses of air-supported membrane structures are observed to significantly increase with lower internal pressures, higher wind speeds, more incoming turbulence, and less membrane tensile stiffness. Two distinct patterns of wind response, buffeting, and aeroelastic instability, are observed within the aeroelastic wind tunnel experiments. These two patterns exhibit significant differences in terms of fluid–structure interaction mechanisms and statistics of structural wind responses. This research emphasizes the influences of membrane elasticity and incoming turbulence on variations of structural wind response patterns. Aeroelastic instability is observed on models with extreme flexibility and relatively lower incoming turbulence, while the buffeting pattern is observed with other configurations, including cases that approach the similarity requirements for simulating air-supported membrane structures in practice.

Growth and instability in edible oilseeds in India: A temporal analysis

In the field crops section, oilseeds are the second most significant crop after the cereals making them a vital determinant of the agrarian economy. India is one of the leading producer nations of oilseeds globally, but domestic production of edible oil fails to match the rising demands, leading to a considerable rise in the edible oil imports over time. India imports 60 per cent of its annual edible oil requirement. The rich agro-ecological diversity of India is suitable to grow a variety of oilseeds. Once an oil-exporting nation, India has now turned to be an oil-importer country majorly due to widened demand-supply gap, with low productivity being the prime cause for the mismatch. This paper is envisioned to study the growth and instability pattern of edible oilseedsfrom1970-71 to 2017-18. Area observed a declining trend, whereas production showed little growth due to low productivity. Soybean observed the highest growth among seven edible oilseeds. Sunflower showed the highest instability index followed by safflower. Period I exhibited the highest instability, which reduced in further periods as a result of the launch of various oilseed development schemes. Yield effect was the chief contributor to the growth in production of rapeseed-mustard,groundnut, and sesame, whereas area effect boosted the production of soybean, sunflower, safflower, and niger.

Nonlethal Furfural Exposure Causes Genomic Alterations and Adaptability Evolution in Saccharomyces cerevisiae.

Furfural is a major inhibitor found in lignocellulosic hydrolysate, a promising feedstock for the biofermentation industry. In this study, we aimed to investigate the potential impact of this furan-derived chemical on yeast genome integrity and phenotypic evolution by using genetic screening systems and high-throughput analyses. Our results showed that the rates of aneuploidy, chromosomal rearrangements (including large deletions and duplications), and loss of heterozygosity (LOH) increased by 50-fold, 23-fold, and 4-fold, respectively, when yeast cells were cultured in medium containing a nonlethal dose of furfural (0.6 g/L). We observed significantly different ratios of genetic events between untreated and furfural-exposed cells, indicating that furfural exposure induced a unique pattern of genomic instability. Furfural exposure also increased the proportion of CG-to-TA and CG-to-AT base substitutions among point mutations, which was correlated with DNA oxidative damage. Interestingly, although monosomy of chromosomes often results in the slower growth of yeast under spontaneous conditions, we found that monosomic chromosome IX contributed to the enhanced furfural tolerance. Additionally, terminal LOH events on the right arm of chromosome IV, which led to homozygosity of the SSD1 allele, were associated with furfural resistance. This study sheds light on the mechanisms underlying the influence of furfural on yeast genome integrity and adaptability evolution. IMPORTANCE Industrial microorganisms are often exposed to multiple environmental stressors and inhibitors during their application. This study demonstrates that nonlethal concentrations of furfural in the culture medium can significantly induce genome instability in the yeast Saccharomyces cerevisiae. Notably, furfural-exposed yeast cells displayed frequent chromosome aberrations, indicating the potent teratogenicity of this inhibitor. We identified specific genomic alterations, including monosomic chromosome IX and loss of heterozygosity of the right arm of chromosome IV, that confer furfural tolerance to a diploid S. cerevisiae strain. These findings enhance our understanding of how microorganisms evolve and adapt to stressful environments and offer insights for developing strategies to improve their performance in industrial applications.

Electrocardiographic patterns of autonomic dysfunction in the diagnosis of autonomic neuropathy in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus poses a serious threat to the health of people worldwide. Despite active detection and stringent measures to control and treat diabetes, the condition leads to a variety of complications, including autonomic neuropathy, resulting in autonomic cardiac denervation associated with an increased risk of painless myocardial ischemia and sudden cardiac death. However, digital verification by finding electrocardiographic (ECG) patterns of autonomic dysfunction is possible.
 The available literature on ECG patterns of myocardial electrical instability, which reflect autonomous myocardial dysfunction, was summarized. A literature review of scientific papers on ECG diagnosis of autonomic myocardial dysfunction in patients with type 2 diabetes mellitus over the past 5 years was performed using PubMed and eLIBRARY data.
 Among different ECG patterns that reflect autonomic dysfunction, the most common is the investigation of heart rhythm variability, which is based on the mathematical analysis of respiration rate intervals. The simplest variables are used to obtain a series of statistical indicators such as SDANN, RMSSD, NN50, and pNN50. A new and understudied ECG pattern of autonomic dysfunction is heart rate turbulence (HRT), which is a short-term rhythm change that develops in response to a ventricular extrasystole. The extrasystole is followed by a short episode of sinus tachycardia lasting several cardiac cycles, which is followed by a longer episode of bradycardia. These heart rate fluctuations are based on baroreflex compensation of intracardiac hemodynamic changes. Two parameters are estimated to characterize the HRT: turbulence onset and turbulence slope. A specific marker of autonomic dysfunction is the rate of cardiac rhythm recovery after controlled exercise. A recovery rate of 12 beats per first minute was associated with an increased risk of all-cause mortality, whereas a reduction in recovery rate of 40 beats per 2 min was found to be a strong independent risk factor for all-cause mortality.
 An imbalance in the tone of sympathetic and parasympathetic systems underlies all the described indicators. Therefore, a risk-stratifying significance of autonomic dysfunction markers in a wide range of pathologies, including peptic ulcer disease, gallstone disease, hypertension, chronic heart failure, chronic obstructive pulmonary disease, bronchial asthma, thyreopathies, and anemias apart from type 2 diabetes mellitus, exists. This explains the high sensitivity of tests, while having a low positive predictive value and specificity. The ease of performing tests dictates the need for further study of the features of autonomic dysfunction markers in patients with type 2 diabetes mellitus, since these markers are associated with a high risk of painless myocardial ischemia and sudden cardiac death.
 Currently, several ECG patterns (heart rate variability, HRT, and heart rate recovery rate) reflect autonomous myocardial dysfunction. The patterns enable early detection of autonomous neuropathy in patients with type 2 diabetes mellitus, which will allow timely diagnosis and adequate therapy. However, further study is required due to their low specificity to identify the peculiarities in specific nosological forms.

Imaging Diagnosis and Management of Carpal Trauma and Instability-An Illustrated Guide.

Understanding the subtle signs of carpal instability and other unique injury patterns in the wrist is a critical skill for radiologists. Proper patient management and outcomes are directly dependent on the accurate interpretation of wrist imaging studies. This review will provide a detailed overview of typical imaging features of carpal trauma and instability, management, and complications, using multimodality imaging and original medical illustrations. A detailed overview of the osseous, ligamentous, arterial anatomy of the wrist, arcs of Gilula, and zones of vulnerability will be provided. Carpal fractures, dislocations, special radiographic views, and imaging pearls will be discussed. Instability patterns and the myriad of associate abbreviations (CID, CIND, CIC, CIA, VISI, DISI, SLD, LTD, MCI, SLAC, SNAC) will be clarified. Expected outcomes, potential complications, and management will be reviewed.

Relationship between flight muscle dimorphism and wing morphometry in Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae, Triatominae)

Triatoma infestans, the primary vector of Chagas disease in southern South America, is reported as a dimorphic species for flight muscle development and presents a marked phenotypic plasticity in traits related to flight. In triatomines, studying the relationship between flight muscle development and wing variation is important, since it involves flight capacity and dispersion. Therefore, we examined the association between flight muscle dimorphism and morphological wing variation in T. infestans individuals. We hypothesized that if the underdeveloped flight muscle were associated with a decrease in wing developmental stability, canalization and morphological aspect of wings, and with a loss of wing modularity, then wing variation would be associated with flight muscle dimorphism. Wing size and shape were characterized using geometric morphometrics. Patterns of canalization, developmental instability, and modularity were inferred from fluctuating asymmetry analysis of wing shape. Morphological aspects of wings were estimated using maximum wing length and wing area. The results showed that there are differences in wing shape but not in wing size among groups. Canalization and developmental stability were positively associated in individuals with muscle development and negatively associated in individuals with underdeveloped flight muscles. The covariance structure of variation among individuals was different between groups but not for fluctuating asymmetry, both for females and males. Modularity hypothesis related to the wing subdivision into two parts, a stiff part and a membranous one, showed significant association for the variation among individuals and fluctuating asymmetry variation in females with flight muscles. Wing aspect showed that females with flight muscles exhibited more elongated and thinner wings than those without flight muscles. The results obtained in this study reveal an association between flight muscle development and forewing variation in T. infestans. Females with flight muscles have certain differential characteristics in their wings that would be related to an enhanced flight performance.

Serum Uric Acid Levels Are Associated with the Echogenic Features of Carotid Plaque Vulnerability in Elderly Patients with Atherosclerotic Disease.

Uric acid is a marker of inflammation and a risk factor for atherosclerosis that has been suggested to play a role in carotid plaque instability. Reduced atherosclerotic plaque echogenicity at ultrasound examination is associated with alarming histopathological features and inflammation. In this study, we investigated the relationship between serum uric acid (SUA) levels and echogenic patterns of plaque instability in elderly subjects with carotid atherosclerosis. Since uric acid metabolism largely depends on renal function, SUA levels were indexed for serum creatinine levels (SUA/SCr). We enrolled 108 patients aged 65 years or more (72.7 ± 5.9 years; 50 females and 58 males) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by greyscale median (GSM). The regression analysis demonstrated a significant inverse association between the GSM and the SUA/SCr ratio (β: -0.567; 95% CI -0.751 to -0.384 and p < 0.0001). Stepwise multivariate regression showed that the SUA/SCr ratio explained 30.3% of GSM variability (β: -0.600; 95% CI -0.777/-0.424, p < 0.0001, and semi-partial correlation 0.303). After a mean period of 3.5 ± 0.5 years, 48 patients were reevaluated according to the same baseline study protocol. The regression analysis demonstrated a still significant inverse association between the GSM and the SUA/SCr ratio (β: -0.462; 95% CI -0.745 to -0.178 and p = 0.002). Stepwise multivariate regression showed that the SUA/SCr ratio explained 28.0% of GSM variability (coefficient -0.584, 95% CI -0.848/-0.319, p < 0.0001, and semi-partial R2 0.280). In conclusion, this study demonstrates that SUA levels indexed for serum creatinine are associated with the echogenic features of carotid plaque vulnerability in elderly patients with atherosclerotic disease. These data could suggest an influential role for uric acid metabolism in carotid plaque biology.

Study of Water–Sand Inrush through a Vertical Karst Conduit Uncovered through Tunnel Excavation

The existence of karst compromises the safety of underground engineering, especially during tunnel excavations. Karst conduits are uncovered through tunnel excavations, which may lead to a water–sand inrush disaster. Taking a vertical karst conduit as an example, the process of water–sand inrush through a karst conduit could be viewed as being similar to the process whereby a water–sand mixture flows through the discharge opening of a storage bin. In this study, based on force analysis of a non-aqueous sand body above a karst conduit, the limiting diameter of the karst conduit under force equilibrium was obtained. Considering the effect of water on aqueous sand bodies, the criterion of water–sand inrush was established. We aimed to study water–sand migration and inrush through vertical karst conduits in order to obtain the distribution of the water pressure near a vertical karst conduit, and to explore the relationship between the conduit size, water pressure, and water–sand flow rate; therefore, a simulated testing system for analyzing water–sand inrush through a vertical karst conduit was developed. When the water pressure in the testing chamber was close to the critical head pressure of the water–sand inrush, the water–sand inrush exhibited a pattern of instability—migration—deposition—stability. When the water pressure in the testing chamber exceeded the critical head pressure, the water–sand flow increased first and then stabilized over time. With the increase in the set values of the water pressure and conduit size, the steady flow of the water–sand mixture increased gradually. When the karst conduit was opened suddenly, the actual water pressure in the testing chamber decreased significantly, due to the water–sand mixture flowing out of the testing chamber and the water supply lagging behind. With the stabilization of the water–sand flow, the actual water pressure gradually tended towards stability, but it was still lower than the initial set water pressure. When the karst conduit was opened, the values of the water pressure monitored by the pore pressure gauges all clearly decreased. With the stabilization of the water–sand flow, the water pressure gradually became stable. With the increase in the distance between the pore pressure sensor and the karst conduit, the water pressure values all increased gradually. These test results are significant for further studies of the formation mechanisms of water–sand inrush through vertical karst conduits.

Atypical Shoulder Instability Patterns in Adolescents Following Traumatic Anterior Shoulder Dislocation

Background: Traumatic anterior shoulder instability is common in the adolescent athlete, and when it is untreated, the recurrence rate is high. Atypical lesions—such as anterior glenoid periosteal sleeve, humeral glenohumeral ligament, and insertional tendon avulsions—may occur within this population, and accurate diagnosis and appropriate lesion management are key to treatment success. Purpose: To evaluate the age, skeletal immaturity, bone loss, and uncommon soft tissue lesions as correlates of posttraumatic anterior shoulder instability lesion patterns in an adolescent population. Study Design: Cross-sectional study, Level of evidence, 3. Methods: Consecutive patients ≤18 years of age (160 shoulders) treated within a single institution for traumatic anterior shoulder instability between June 2013 and June 2021 were reviewed. Demographics, injury mechanism, radiographic and magnetic resonance imaging of lesions, the presence of any bone loss, operative findings, and physeal status were recorded. An overall 131 shoulders met the inclusion criteria. Instability lesion type was analyzed categorically by age <15 or ≥15 years; individual age was assessed for correlation with any bone loss present. Atypical lesions—anterior labral periosteal sleeve avulsion, humeral avulsion of the glenohumeral ligament, subscapularis avulsion—were assessed for correlations with age, open physeal status, and the presence of any bone loss. Results: An overall 131 shoulders (mean, 15.3 years; range, 10.5-18.3) were identified for this study: 55 in patients <15 years old and 76 in patients ≥15 years old. Bony injuries such as Bankart and Hill-Sachs lesions were more common in the ≥15-year-old group (P = .044 and P = .024, respectively). Bony Bankart injuries were found at a rate of 18.2% in the <15-year-old group, as compared with 34.2% in the ≥15-year-old group (P < .05). Anterior labral periosteal sleeve avulsions were more common in the <15-year-old group (n = 13 [23.6%] vs n = 8 [10.5%]; P < .044), as were all atypical lesions combined (n = 23 [41.8%] vs n = 13 [17.1%]; P < .0018]. Conclusion: In this series of anterior shoulder instability in children and adolescents, instability lesions varied significantly by age. Bone loss was associated with older age at presentation, and atypical lesions were more common in patients <15 years of age. Treatment teams should be aware of less common soft tissue injuries in this young age group and ensure careful review of adequate imaging for proper diagnosis and treatment in these younger patients.

Evaluating the Role of Land Surface Moisture in Generating Asymmetrical Precipitation during the Landfall of Hurricane Florence (2018)

This study focuses on the role of land surface moisture in generating asymmetrical precipitation surrounding a nearly stationary Hurricane Florence (2018) during landfall. Previous idealized modeling studies have suggested that atmospheric stability varies surrounding a tropical cyclone (TC) during landfall, with the atmosphere destabilizing off-shore and stabilizing on-shore. However, this finding has not been studied using a real modeling framework. Here, we produce high-resolution numerical simulations to examine the variations in precipitation and atmospheric stability surrounding Hurricane Florence. In addition to a control simulation (CTRL), two additional simulations are performed by altering the land surface cover to be moister (WETX) or drier (DRYX) compared with the CTRL. In the experiment, the altered land surface affects the equivalent potential temperature within the boundary layer. Due to changes in moisture, there are consistent but minor impacts on the spatial patterns of moist static instability. This study found that rainbands in the inner core and distant rainband regions responded differently to changes in land surface moisture. Within the inner core region of the TC, WETX produced more precipitation that was more symmetrical compared with DRYX. In DRYX, there was increased moist static instability in the outer rainband region over water and decreased moist static instability in the outer rainband region over land, which may have contributed to the enhanced precipitation asymmetries. Still, both experiments produced asymmetrical precipitation distributions, suggesting that alterations to land surface moisture had a minor impact on the precipitation asymmetries in Hurricane Florence. We conclude that precipitation asymmetries are primarily dynamically driven by weak to moderate vertical wind shear and asymmetries in moisture flux convergence.

New patterns of genetic instability in chronic myeloid leukemia: interesting, but not ready for clinical use.

Not available.

OBJECTIVELY MEASURED KNEE INSTABILITY DURING PIVOT-SHIFT TEST: AN EXPERIMENTAL DYNAMIC RSA STUDY

The Pivot-shift test is a clinical test for knee instability for patinets with Anterior cruciate ligament (ACL), however the test has low inter-observer reliability. Dynamic radiostereometry (dRSA) imaging is a highly precise method for objective evaluation of joint kinematics. The purpose of the study was to quantify precise knee kinematics during Pivot-shift test by use of the non-invasive dynamic RSA imaging.Eight human donor legs with hemipelvis were evaluated. Ligament lesion intervention of the ACL was performed during arthroscopy and anterolateral ligament (ALL) section was performed as a capsular incision. Pivot-shift test examination was recorded with dRSA on ligament intact knees, ACL-deficient knees and ACL+ALL-deficient knees.A Pivot-shift pattern was identifyable after ligament lesion as a change in tibial posterior drawer velocity from 7.8 mm/s in ligament intact knees, to 30.4 mm/s after ACL lesion, to 35.1 mm/s after combined ACL-ALL lesion. The anterior-posterior drawer excursion increased from 2.8 mm in ligament intact knees, to 7.2 mm after ACL lesion, to 7.6 mm after combined lesion. Furthermore a change in tibial rotation was found, with increasing external rotation at the end of the pivot-shift motion going from intact to ACL+ALL-deficient kneesThis experimental study demonstrates the feasibility of RSA to objectively quantify the kinematic instability patterns of the knee during the Pivot-shift test. The dynamic parameters found through RSA displayed the kinematic changes from ACL to combined ACL-ALL ligament lesion.

Abstract 3556: Assessing patterns of genomic instability in recurrent osteosarcoma

Abstract Objective: The osteosarcoma genome is characterized by high levels of genomic instability, however whether there is pervasive ongoing genomic instability, or instability introduced by an early catastrophic event, is still unsettled. Methods: We performed 30-80x whole genome sequencing (WGS) of 37 tumor samples from 8 patients with relapsed or refractory osteosarcoma. Each patient had at least one sample from a primary site and one sample from a metastatic or relapse site. A set of high confidence single nucleotide variants (SNV), copy number alterations (CNA), structural variations (SV) were called for each sample using our pediatric expanded genomics pipeline and an analysis focused on markers of genomic instability was performed using a custom pipeline of computational tools. Results: Of the 8 patients in our cohort, 4 had localized disease at diagnosis (OSCE4, OSCE5, OSCE6, OSCE9) and 4 had metastatic disease at diagnosis (OSCE1, OSCE2, OSCE3, OSCE10). There were 17 samples from primary sites, 7 pretreatment biopsies, 10 on therapy primary resections, 20 metastatic sites, 15 of which were from lung metastases. We have previously reported on the clonal evolution regarding SNVs and CNAs within this cohort. TP53 structural variants involving intron 1/2 were seen in 6/8 patients (OSCE2, OSCE3, OSCE4, OSCE6, OSCE9, OSCE10). No new structural variants in consensus driver genes emerged in metastatic or relapse samples. Comparing the earliest sample to most recent sample in each patient, only OSCE1, OSCE9, and OSCE10 demonstrated an increase of ≥100 structural variants at the final timepoint. In OSCE2, OSCE5, and OSCE6, there were less structural variants identified at the final timepoint when compared to the earliest timepoint. Homologous recombination deficiency (HRD) scores were calculated for each sample. Only 4/8 patients (OSCE3, OSCE4, OSCE9, OSCE10) had an HRD score in the most recently acquired sample higher than the score from the primary site. Regions of hypermutation consistent with kataegis were identified for each sample, with the number of kataegis events remaining unchanged or decreasing in some instances. Kataegis events co-localized with rearrangement events a majority of the time (range 50-100%, Avg= 72.6%). Complex rearrangements such as chromothripsis and chromoplexy were assesed. In 6 patients there were &amp;gt; 9 chromosomal arms involved in complex rearrangements that were shared between primary sites and metastatic/recurrent sites, while ≤ 4 chromosomal arms were involved with new complex rearrangements unique to the metastatic sites. Conclusion: The patterns observed in our cohort reveal that osteosarcoma is relatively stable from diagnosis through subsequent relapses, supporting the model that an early catastrophic event accounts for the genomic instability observed in osteosarcoma. Citation Format: Michael David Kinnaman, Simone Zaccaria, Alvin Makohon-Moore, Gunes Gundem, Juan E. Arango Ossa, Filemon S. Dela Cruz, Paul A. Meyers, Meera Hameed, William D. Tap, Julia Lynne Glade Bender, Elli Papaemmanuil, Andrew Kung, Christine Iacobuzio Donahue. Assessing patterns of genomic instability in recurrent osteosarcoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3556.

“It's no foundation, there's no stabilization, you're just scattered”: A qualitative study of the institutional circuit of recently-evicted people who use drugs

People who use drugs (PWUD) commonly experience housing instability due to intersecting structural vulnerabilities (e.g., drug prohibition, discriminatory housing policies), and prejudicial or illegal evictions are common. In Vancouver, Canada, evictions have proliferated in the Downtown Eastside, a historically low-income neighbourhood with high rates of drug use and housing instability, resulting in many PWUD being evicted into homelessness. This study characterizes housing trajectories of recently-evicted PWUD through the lens of the institutional circuit of homelessness, and explores how wider contexts of structural vulnerability shape experiences within this. Qualitative interviews were conducted with PWUD recently evicted in the Downtown Eastside (<60 days). Peer research assistants recruited 58 PWUD through outreach activities. All PWUD participated in baseline interviews on the causes and contexts of evictions. Follow-up interviews were completed with 41 participants 3–6 months later, focusing on longer-term impacts of eviction, including housing trajectories. Most participants were evicted into homelessness, remaining so at follow-up. Participants described patterns of residential instability consisting of frequent cycling between shelters, streets, and kin-based networks. While participants normalized this cycling as characteristic of their marginalized social positions, narratives revealed how the demands of the institutional circuit deepened vulnerabilities and prolonged experiences of homelessness. Experiences were framed by participants' (in)ability to navigate survival needs (e.g., shelter, drug use), with tensions and trade-offs between needs increasing participants' and their peers' risks of harms. Constructions of agency further shaped experiences; accounts highlighted tensions between the control inherent to indoor spaces and participants’ need for autonomy. Findings demonstrate how the demands of the institutional circuit foregrounded structural vulnerabilities to perpetuate cycles of instability. Interventions that address survival needs and preserve agency will be necessary to mitigate risks within the institutional circuit, in tandem with upstream interventions that target housing vulnerability and broader social-structural conditions (e.g., poverty, affordability) that entrap recently-evicted PWUD in the institutional circuit.

Molecular markers as predictors of response to perioperative chemotherapy in locally advanced gastric cancer

Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p &lt;0.0001). There was no association between an increase in KRAS copy number and objective response rate (p = 1.0). For microsatellite instability and other studied markers no statistically significant correlation with progression-free survival and objective response rate was found (p &gt;0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.

Learning non-stationary and discontinuous functions using clustering, classification and Gaussian process modelling

Surrogate models have shown to be an extremely efficient aid in solving engineering problems that require repeated evaluations of an expensive computational model. They are built by sparsely evaluating the costly original model and have provided a way to solve otherwise intractable problems. A crucial aspect in surrogate modelling is the assumption of smoothness and regularity of the model to approximate. This assumption is however not always met in reality. For instance in civil or mechanical engineering, some models may present discontinuities or non-smoothness e.g., in case of instability patterns such as buckling or snap-through. Building a single surrogate model capable of accounting for these fundamentally different behaviours or discontinuities is not an easy task. In this paper, we propose a three-stage approach for the approximation of non-smooth functions which combines clustering, classification and regression. The idea is to split the space following the localized behaviors or regimes of the system and build local surrogates that are eventually assembled. A sequence of well-known machine learning techniques are used: Dirichlet process mixtures models (DPMM), support vector machines and Gaussian process modelling. The approach is tested and validated on two analytical functions and a finite element model of a tensile membrane structure.

Advancements of phonetics in the 21st century: Theoretical and empirical issues in the phonetics of sound change

It has long been understood that speakers produce and listeners perceive non-random, systematic phonetic variants that serve as the raw material for sound change. This understanding underlies much of the current research on the phonetic underpinnings of change, which includes study of (i) general phonetic principles underlying variation, (ii) specific phonetic ‘preconditions’ and biases arguably linked to specific patterns of phonological instability and change, and (iii) the production and perception of variation by speaker-listeners in situations of actual ongoing change and by interacting agents in computational simulations of change. This paper shows how findings from these three broad areas of study have led to 21st century theoretical and empirical advancements in our understanding of phonetic change. Big-picture questions about the nature of change are approached through consideration of a series of smaller, more tractable questions (e.g., about the nature of, and relation between, innovative speaking and innovative listening for both stable patterns of variation and ongoing change). The paper’s goals are to show, for these questions, their theoretical grounding, empirical challenges, preliminary answers and, in turn, the new theoretical directions emerging from those answers.

Study Features and Response Compliance in Ecological Momentary Assessment Research in Borderline Personality Disorder: Systematic Review and Meta-analysis.

Borderline personality disorder (BPD) is characterized by frequent and intense moment-to-moment changes in affect, behavior, identity, and interpersonal relationships, which typically result in significant and negative deterioration of the person's overall functioning and well-being. Measuring and characterizing the rapidly changing patterns of instability in BPD dysfunction as they occur in a person's daily life can be challenging. Ecological momentary assessment (EMA) is a method that can capture highly dynamic processes in psychopathology research and, thus, is well suited to study intense variability patterns across areas of dysfunction in BPD. EMA studies are characterized by frequent repeated assessments that are delivered to participants in real-life, real-time settings using handheld devices capable of registering responses to short self-report questions in daily life. Compliance in EMA research is defined as the proportion of prompts answered by the participant, considering all planned prompts sent. Low compliance with prompt schedules can compromise the relative advantages of using this method. Despite the growing EMA literature on BPD in recent years, findings regarding study design features that affect compliance with EMA protocols have not been compiled, aggregated, and estimated. This systematic meta-analytic review aimed to investigate the relationship between study design features and participant compliance in EMA research of BPD. A systematic review was conducted on November 12, 2021, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines to search for articles featuring EMA studies of BPD that reported compliance rates and included sufficient data to extract relevant design features. For studies with complete data, random-effect models were used to estimate the overall compliance rate and explore its association with design features. In total, 28 peer-reviewed EMA studies comprising 2052 participants were included in the study. Design features (sampling strategy, average prompting frequency, number of items, response window, sampling device, financial incentive, and dropout rate) showed a large variability across studies, and many studies did not report design features. The meta-analytic synthesis was restricted to 64% (18/28) of articles and revealed a pooled compliance rate of 79% across studies. We did not find any significant relationship between design features and compliance rates. Our results show wide variability in the design and reporting of EMA studies assessing BPD. Compliance rates appear to be stable across varying setups, and it is likely that standard design features are not directly responsible for improving or diminishing compliance. We discuss possible nonspecific factors of study design that may have an impact on compliance. Given the promise of EMA research in BPD, we also discuss the importance of unifying standards for EMA reporting so that data stemming from this rich literature can be aggregated and interpreted jointly.

Dysregulation of AMPA Receptor Trafficking and Intracellular Vesicular Sorting in the Prefrontal Cortex of Dopamine Transporter Knock-Out Rats.

Dopamine (DA) and glutamate interact, influencing neural excitability and promoting synaptic plasticity. However, little is known regarding the molecular mechanisms underlying this crosstalk. Since perturbation of DA-AMPA receptor interaction might sustain pathological conditions, the major aim of our work was to evaluate the effect of the hyperactive DA system on the AMPA subunit composition, trafficking, and membrane localization in the prefrontal cortex (PFC). Taking advantage of dopamine transporter knock-out (DAT-/-) rats, we found that DA overactivity reduced the translation of cortical AMPA receptors and their localization at both synaptic and extra-synaptic sites through, at least in part, altered intracellular vesicular sorting. Moreover, the reduced expression of AMPA receptor-specific anchoring proteins and structural markers, such as Neuroligin-1 and nCadherin, likely indicate a pattern of synaptic instability. Overall, these data reveal that a condition of hyperdopaminergia markedly alters the homeostatic plasticity of AMPA receptors, suggesting a general destabilization and depotentiation of the AMPA-mediated glutamatergic neurotransmission in the PFC. This effect might be functionally relevant for disorders characterized by elevated dopaminergic activity.

Two paths towards job instability: Comparing changes in the distribution of job tenure duration in the United Kingdom and Germany, 1984–2014

AbstractThis study provides novel evidence on trends in job stability in the United Kingdom and Germany, two capitalist economies with distinct sets of institutions and labour market reform trajectories. While we find evidence of an increase in short‐term jobs for men in both countries, we also find important differences in the overall patterns of change in the distribution of job tenure duration. The United Kingdom follows a masked instability pattern with opposite job stability trends for men and women. On the other hand, we find evidence of a polarization of the job tenure distribution among men and women in Germany. These findings are partly consistent with expectations from the dualization literature, emphasizing a growing segmentation of the labour market between insiders and outsiders. More generally, this study highlights the existence of multiple paths towards increased job instability that appear to be rooted in institutional differences.