This paper shall explore the reasons that triggered China to boost its security and economic influence within the United Nations Peacekeeping Operations (UNPKO) as a tool for embracing international challenges. By doing so, China is not just sharing the burden of providing international stability and achieving the UN Sustainable Development Goals, but exerting its influence in the process. Analysing the proposed subject, it will be demonstrated that China faces numerous obstacles whilst trying to insert the “Chinese characteristics” within the geopolitical order, geo-economics distribution of wealth and international security architecture. Instead of being perceived as a responsible stakeholder, China`s ambitious initiatives can, additionally, stir the China Threat Theory in the international community. This paper shall be consisted of two parts. The first part will tackle China`s growing footprint within the UNPKO from the end of the Cold War onward. The second part will explore the reasons that triggered China to swift its role within the UNPKO. Both global and domestic reasons will be analysed too.

Background and study aims Endoscopic ultrasound-guided through-the-needle biopsy (TTNB) of pancreatic cystic lesions (PCLs) is associated with a non-negligible risk for adverse events (AEs). We aimed to identify the hierarchic interaction among independent predictors for TTNB-related AEs and to generate a prognostic model using recursive partitioning analysis (RPA). Patients and methods Multicenter retrospective analysis of 506 patients with PCLs who underwent TTNB. RPA of predictors for AEs was performed and the model was validated by means of bootstrap resampling. Results Mean cysts size was 36.7mm. Most common diagnoses were intraductal papillary mucinous neoplasm (IPMN, 45%), serous cystadenoma (18.8%), and mucinous cystadenoma (12.8%). Fifty-eight (11.5%) AEs were observed. At multivariate analysis, age (odds ratio [OR] 1.32, 1.09-2.14; p=0.05), number of TTNB passes (OR from 2.17, 1.32-4.34 to OR 3.16, 2.03-6.34 with the increase of the number of passes), complete aspiration of the cyst (OR 0.56, 0.31-0.95; p=0.02), and diagnosis of IPMN (OR 4.16, 2.27-7.69; p<0.001) were found to be independent predictors of AEs, as confirmed by logistic regression and random forest analyses. RPA identified three risk classes: high-risk (IPMN sampled with multiple microforceps passes, 28% AEs rate), low-risk (1.4% AE rate, including patients <64 years with other-than-IPMN diagnosis sampled with ≤2 microforceps passes and with complete aspiration of the cyst) and middle-risk class (6.1% AEs rate, including the remaining patients). Conclusion TTNB should be selectively used in the evaluation of patients with IPMN. The present model could be applied during patient selection as to optimize the benefit/risk of TTNB.

This paper provides an overview of the seven possible hand-related traits, with an idea to estimate the statistical phenotypic association between them. The traits observed in this study were: midphalangeal hair, Hitchhiker’s thumb, extensibility of proximal joint of thumb, digital index, nail shape, crooked fifth finger and hand clasping. The mentioned characteristics were observed in 7431 unrelated subjects, with approximately equal gender distribution. For each case, three groups were formed: total, male and female. The subjects were evenly distributed throughout Bosnia and Herzegovina’s various geographical regions, and they properly represent the country’s national and ethnic composition. The Chi-squared test was used to determine the statistical significance of the association between these traits, while Fisher’s exact test was utilized as an extra test to analyze the association between each pair of observed features. Also, Chi-squared test was applied for observing differences in the frequencies of the phenotypic characteristics of the hand between the genders. Following traits were shown to have a statistically significant association: midphalangeal hair-Hitchhiker’s thumb, midphalangeal hair – digital index, midphalangeal hair – nail shape, midphalangeal hair – crooked fifth finger, Hitchhiker’s thumb- extensibility of proximal joint of thumb, digital index – nail shape, digital index -crooked fifth finger, midphalangeal hair – hand clasping, crooked fifth finger – hand clasping. Analysis of differences in the frequencies of the observed phenotypic traits of the hand according to the genders showed statistical significance for D, Dht, Ref and Lf.

Every human activity, regardless of its nature, type and other specifics, strives to achieve the highest possible efficiency. In that sense, it is necessary to observe the tendency of the efficiency of criminal proceedings in terms of clarifying and resolving certain criminal matters, as well as making a court decision. The efficiency of the criminal procedure is directly manifested and articulated through the criminal procedure activities that are undertaken by the criminal procedure subjects during the realization of the criminal procedure task. The intention of the authors is to recognize, identify and emphasize the key or most important aspects of the qualitative component in the work of the main and secondary criminal procedure subjects on which the efficiency of the criminal procedure directly depends. Also, attention and interest are focused on the mutual relationship, interaction and opposition of two tendencies, namely tendencies of efficiency of criminal procedure and tendencies of protection of basic human rights and freedoms with special reference to meeting the standard of proof in different phases of undertaking criminal proceedings.

Castleman disease (CD) describes a group of heterogeneous lymphoproliferative disorders with characteristic histopathology that are classified based on the number of enlarged lymph node (LN) stations, etiological drivers, and clinical phenotype. CD histopathology includes a broad spectrum from plasmacytic to hyaline/hyper vascular with a mixed pattern in between. Unicentric CD (UCD) involves a single enlarged LN station and mild symptoms, whereas multicentric CD (MCD) involves multiple stations of enlarged LNs and more severe symptoms. MCD is subclassifed into Human Herpesvirus-8 associated MCD, POEMS-associated MCD, and idiopathic MCD (iMCD). iMCD cases are further subdivided into thrombocytopenia, anasarca, fever/elevated C-reactive protein (CRP), renal dysfunction, organomegaly (TAFRO) or iMCD-not otherwise specified (NOS), who often have thrombocytosis and hypergammaglobulinemia. Recently, it has been reported that some iMCD patients can have more oligocentric lymphadenopathy (above or below the diaphragm) whereas others have generalized lymphadenopathy (above and below the diaphragm). Given the heterogeneity across CD, we leveraged data from a longitudinal natural history study of CD to characterize the spectrum of CD. Specifically, we set out to determine if patients with multicentric lymphadenopathy localized to above or below the diaphragm (oligocentric CD, OCD) appeared to be more similar to UCD or iMCD with more generalized lymphadenopathy. In total, 130 patients enrolled in an international CD registry were confirmed to have CD by a panel of experts. Patients were assigned UCD, OCD, or iMCD per the following: UCD, 1 station of enlarged LNs (N=32); OCD, ≥2 stations of enlarged LNs, either above or below the diaphragm (N=29); iMCD, ≥2 stations of enlarged LNs, both above and below the diaphragm (N=69). Clinical data is provided closest to date of diagnosis +/-90 days. Sustained response is defined as ≥50% symptom improvement sustained without the addition of subsequent drug treatments. When appropriate, statistical testing was performed by Chi-square, Fisher's exact, or two-tailed T test. Among the 69 iMCD patients, 42 (61%) were classified as TAFRO and 27 (39%) were NOS. In contrast, only 1 of 29 OCD patients (3%) was TAFRO and 28 (97%) were NOS. No UCD patients were TAFRO. Breakdown of histopathological subtype can be found in Table 1. There was a mean (SD) of 8.4 (3.7) enlarged LNs in iMCD at diagnosis, compared with 2.8 (1.4) in OCD and 1 (0) in UCD. While enlarged LNs in the abdomen/pelvis region occurred in 56% of UCD, only 19% of OCD patients demonstrated lymphadenopathy in this region. Clinically, OCD patients demonstrated symptoms and laboratory abnormalities more comparable to UCD than iMCD (Table 2). In fact, there was no difference in symptoms between UCD and OCD groups, while there were significantly more symptoms in iMCD than OCD. iMCD had significantly worse anemia, albumin, creatinine, CRP, and other markers of inflammation than OCD, whereas OCD patients had significantly increased CRP (p=0.03) and alkaline phosphatase (p=0.03) compared to UCD. IgM was greater in OCD than both UCD (p=0.02) and iMCD (p=0.01) (Table 2). The number of patients receiving drug treatments differed by subtype: 7 UCD (22%), 18 OCD (62%), and 67 iMCD (97%). Fifty-five patients (UCD: 1, OCD: 7, iMCD: 47) received anti-IL-6 therapy (+/- steroids), including the only FDA-approved drug, siltuximab. Sustained response to anti-IL-6 (+/- steroids) was observed in 23/47 (49%) iMCD, 3/7 (43%) OCD, and 0/1 UCD. Within iMCD clinical subgroups, response was observed in 12/27 (44%) iMCD-TAFRO and 11/20 (55%) iMCD-NOS as well as across the histopathogical subtypes, suggesting that anti-IL-6 therapy can be effective across the spectrum. Overall, this study highlights the heterogeneity of CD. Importantly, it uncovers a group of CD patients that meet diagnostic criteria for iMCD but their lymphadenopathy is confined to above or below the diaphragm and they appear to behave more similarly to UCD. Given that 1/3 of OCD patients were managed without drug treatment, further work is needed to determine the relative benefits of UCD-like surgical treatment versus iMCD-like drug-based therapy for OCD. The clinical subtype of TAFRO, which was present in more than half of the iMCD patients, was observed in only one OCD case and no UCD cases. Further work is needed to determine optimal treatments across these subgroups. Figure 1 Figure 1. Bagg: Scopio Labs: Research Funding. Lim: EUSA Pharma: Honoraria. Srkalovic: Takeda: Speakers Bureau; Janssen Pharmaceuticals: Speakers Bureau; EUSA Pharma: Speakers Bureau; Foundation Medicine: Speakers Bureau. Uldrick: Merck: Other: Receives study drug; Roche: Research Funding; Regeneron: Current Employment; Celgene: Research Funding. Fajgenbaum: Pfizer: Other: Study drug for clinical trial of sirolimus; N/A: Other: Holds pending provisional patents for 'Methods of treating idiopathic multicentric Castleman disease with JAK1/2 inhibition' and 'Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease'; EUSA Pharma: Research Funding.

Idiopathic multicentric Castleman disease (iMCD) is a rare, life-threatening hematologic disorder involving multi-organ dysfunction driven by inflammatory cytokines, often including interleukin-6 (IL-6). The five-year overall survival rate varies considerably between cohorts, ranging from 50 to 77%. It is not well understood why administration of therapies such as the anti-IL-6 monoclonal antibody siltuximab induces complete and durable remission in some patients, whereas others succumb to their disease despite therapy. The aim of this study was to identify laboratory parameters associated with mortality in iMCD. To this end, iMCD patients enrolled in the ACCELERATE registry with fatal and non-fatal outcomes were compared. To determine differences in the laboratory profiles at time of diagnosis between the non-fatal (control) (n = 66) and fatal (mortality) (n = 6) iMCD groups, we performed two-tailed t-tests with Welch correction. P < 0.05 was considered significant. Due to the exploratory nature of this study and limited sample size, we did not perform correction for multiple comparisons among the 25 parameters assessed. In the fatal iMCD group, all patients were white, aged 15-66, and 33.3% were male. Four patients had a hypervascular histopathological subtype; one subtype was not stated, and one was mixed. The non-fatal iMCD group was mixed race and included 57.6% male patients; 38 patients had a hypervascular subtype, 19 had a mixed subtype, five patients had a plasmacytic subtype, three were not stated and one had a hyaline vascular subtype. The mean time from final diagnosis to death was 586.2 days (range: 16-2952 days). Around the time of diagnosis, immunoglobulin M (IgM) (Figure 1A), international normalized ratio (INR) (Figure 1B), and platelet count (PC) (Figure 1C) were significantly decreased in the fatal group compared with the non-fatal group (Figure 1D), with three mortality patients below the lower limit of normal (LLN) for IgM, and four mortality patients below the LLN for PC. Unlike the other two parameters, the INR levels were closer to normal in the fatal group than the non-fatal group. While C-reactive protein (CRP) levels were higher and hemoglobin (Hb) levels were lower in the mortality group, they did not surpass the significance threshold. These data provide new insights into differences between patients who have fatal and non-fatal outcomes. These preliminary findings from a small cohort of deceased patients demonstrate that patients with iMCD who have fatal outcomes may differ from those who do not. For instance, patients in the fatal group may be in a state of greater immune dysregulation (indicated by a lower IgM) and at increased risk of bleeding events (lower PC), compared with patients who go on to survive. The lower PC in the fatal group is likely reflective of patients with the recently-defined thrombocytopenia, anasarca, fever/elevated CRP, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO) clinical subtype of iMCD having lower platelets and a more aggressive course. Thus, early evaluation of platelet count may be an early and actionable indicator of someone's likelihood of death. Additional research is needed into the role of PC and markers of inflammation and anemia in predicting mortality as well as the timing of decline of these markers. If validated in a larger cohort, certain laboratory values may be of use to identify patients at increased risk of death. Figure 1 Figure 1. Kanhai: EUSA Pharma: Current Employment. Bagg: Scopio Labs: Research Funding. Lim: EUSA Pharma: Honoraria. Srkalovic: EUSA Pharma: Speakers Bureau; Takeda: Speakers Bureau; Foundation Medicine: Speakers Bureau; Janssen Pharmaceuticals: Speakers Bureau. Uldrick: Celgene: Research Funding; Merck: Other: Receives study drug; Roche: Research Funding; Regeneron: Current Employment. Fajgenbaum: EUSA Pharma: Research Funding; Pfizer: Other: Study drug for clinical trial of sirolimus; N/A: Other: Holds pending provisional patents for 'Methods of treating idiopathic multicentric Castleman disease with JAK1/2 inhibition' and 'Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease'.

Building on an in-depth study of a manufacturing company’s shift from a product to a product-service business model, we explore how single-focus companies transition to a dual orientation. Although companies generally use highly sophisticated practices to manage a dual orientation, those that transition to one successfully start with less sophisticated practices. Early on, the use of simple tradeoff practices, which maintain the product and service logics, helps single-focus companies explore the emergent tensions that their transition to a dual orientation causes. Conversely, adopting more sophisticated practices at this early stage overwhelms them. At a later stage, these companies’ growing understanding of the tensions allows them to experiment with more comprehensive paradox practices that transcend the product and service logics. Conversely, maintaining simple practices at this stage prevents them from gaining the solution experience required to complete the transition. The evolutionary process culminates in sophisticated routinized practices that institutionalize recurrent tensions’ solution, while allowing for further experimentation to deal with new tensions. The different practices’ appropriate sequence and pacing during the evolutionary process facilitate companies’ transition to a dual orientation.

While Weighted Lasso sparse regression has appealing statistical guarantees that would entail a major real-world impact in nance, genomics, and brain imaging applications, it is typically scarcely adopted due to its complex high-dimensional space composed by thousands of hyperparameters. On the other hand, the latest progress with high-dimensional hyperparameter optimization (HD-HPO) methods for black-box functions demonstrates that high-dimensional applications can indeed be eciently optimized. Despite this initial success, HD-HPO approaches are mostly applied to synthetic problems with a moderate number of dimensions, which limits its impact in scientic and engineering applications. We propose LassoBench , the rst benchmark suite tailored for Weighted Lasso regression. LassoBench consists of benchmarks for both well-controlled synthetic setups (number of samples, noise level, ambient and eective dimensionalities, and multiple delities) and real-world datasets, which enables the use of many avors of HPO algorithms to be studied and extended to the high-dimensional Lasso setting. We evaluate 6 state-of-the-art HPO methods and 3 Lasso baselines, and demonstrate that Bayesian optimization and evolutionary strategies can improve over the methods commonly used for sparse regression while highlighting limitations of these frameworks in very high-dimensional and noisy settings.

Resistive switching (RS) devices are emerging electronic components that could have applications in multiple types of integrated circuits, including electronic memories, true random number generators, radiofrequency switches, neuromorphic vision sensors, and artificial neural networks. The main factor hindering the massive employment of RS devices in commercial circuits is related to variability and reliability issues, which are usually evaluated through switching endurance tests. However, we note that most studies that claimed high endurances >106 cycles were based on resistance versus cycle plots that contain very few data points (in many cases even <20), and which are collected in only one device. We recommend not to use such a characterization method because it is highly inaccurate and unreliable (i.e., it cannot reliably demonstrate that the device effectively switches in every cycle and it ignores cycle-to-cycle and device-to-device variability). This has created a blurry vision of the real performance of RS devices and in many cases has exaggerated their potential. This article proposes and describes a method for the correct characterization of switching endurance in RS devices; this method aims to construct endurance plots showing one data point per cycle and resistive state and combine data from multiple devices. Adopting this recommended method should result in more reliable literature in the field of RS technologies, which should accelerate their integration in commercial products.

Physically, one tends to think of non-Hermitian systems in terms of gain and loss: the decay or amplification of a mode is given by the imaginary part of its energy. Here, we introduce an alternative avenue to the realm of non-Hermitian physics, which involves neither gain nor loss. Instead, complex eigenvalues emerge from the amplitudes and phase differences of waves backscattered from the boundary of insulators. We show that for any strong topological insulator in a Wigner-Dyson class, the reflected waves are characterized by a reflection matrix exhibiting the non-Hermitian skin effect. This leads to an unconventional Goos-Hänchen effect: due to non-Hermitian topology, waves undergo a lateral shift upon reflection, even at normal incidence. Going beyond systems with gain and loss vastly expands the set of experimental platforms that can access non-Hermitian physics and show signatures associated with non-Hermitian topology.

A insuficiência cardíaca (IC) é uma complexa síndrome clínica de diversas etiologias e com elevada prevalência, caracterizada por falência no suprimento adequado de sangue em relação ao retorno venoso e às necessidades metabólicas do indivíduo, cursando com intolerância ao esforço físico, consequentemente, diminuindo a capacidade funcional. O objetivo deste estudo consiste em comprovar a eficácia da mobilização precoce em pacientes com IC no leito, pelo fisioterapeuta, e ressaltar os benefícios dos exercícios físicos e a melhora na qualidade de vida. Foram realizadas pesquisas bibliográficas nas bases de dados PubMed, SciELO, ProQuest e PEDro, onde foram consultados 10 artigos publicados entre os anos 2009 a 2020. Foram utilizados os seguintes descritores para a busca: Mobilização precoce, Fisioterapia na UTI (Unidade de Terapia Intensiva), Insuficiência cardíaca, Cardiopatias, Treinamento de força e Mobilização precoce na UTI. Dos estudos analisados, os pacientes apresentaram melhora do desempenho funcional, marcha, espasticidade e também na qualidade de vida. A mobilização precoce por meio do fisioterapeuta atua diretamente na reabilitação desses pacientes promovendo ganhos significativos, contribuindo assim de forma bastante eficaz para a sua qualidade de vida.

Response assessment in the treatment of glioblastoma (GB) based on MR-imaging is still challenging, in particular for immunotherapeutic strategies. Several assessment tools have been proposed. In this post-hoc analysis we compared response assessment criteria (MacDonald, RANO, mRANO, Vol.-mRANO, iRANO) in newly diagnosed GB patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression free survival (PFS) and overall survival (OS). 76 patients with newly diagnosed GB enrolled in a multicenter randomized phase II trial receiving standard of care (SOC, n= 40) or SOC + Audencel vaccine (n= 36) were included. Tumor volumes were calculated by semiautomatic segmentation. To detect differences in PFS among the assessment criteria Kruskal-Wallis-test, for correlation analysis Spearman test was used. There was a significant difference in median PFS based on the different assessments (mRANO 8.55 months [9.10-14.03], Vol.-mRANO 8.61 months [9.72-14.92] compared to MacDonald 4.04 months [5.21-8.75] and RANO 4.16 months [5.28-8.61]. For the vaccination arm only, median PFS by iRANO was 5.95 months [5.70-11.54]). There was no difference in PFS between SOC and SOC + Audencel using the different response criteria. The best correlation between PFS and OS was detected for mRANO (r= 0.65, p< 0.001) and Vol.-mRANO (r= 0.69, p< 0.001). At an 8-month landmark, the impact of progressive disease on median OS was best shown for mRANO (13.70 months [13.13-18.98], and Vol.-mRANO 12.03 months [12.51-17.94]) compared to MacDonald 17.97 months [15.45-20.92], RANO 17.97 months [15.92-20.95] and iRANO 17.34 months [14.99-22.73]. When comparing different response assessments in GB patients treated with dendritic cell-based immunotherapy the best correlation between PFS and OS was observed for mRANO and Vol.-mRANO. Overall, no difference in PFS and OS was seen between the two treatment arms. iRANO was not superior for predicting OS in patients treated with Audencel.

Introduction Although extracorporeal shock wave lithotripsy (ESWL) is minimally invasive and highly efficient for the management of kidney stones, adverse effects have been described. Available indicators of renal function exhibit insufficient sensitivity in acute renal injury (AKI). We aimed to evaluate the severity of the kidney tissue response to ESWL injury by measuring the urinary neutrophil gelatinase-associated lipocalin (uNGAL), which can indicate AKI in its early phase. Material and methods The prospective, controlled study included 62 patients with nephrolithiasis undergoing single ESWL treatment. uNGAL level was measured before the procedure, and 6 h and 12 h after. Results The median uNGAL level increased by 126.0%, 6 h after ESWL (p <0.001). The growth rate continued and 12 h after was higher by 583.7%, compared to the pre-treatment level (p <0.001). The median value of estimated glomerular filtration rate (eGFR) dropped by 15.3% 12 h after the treatment (p <0.001). It increased by 5.0% in the period 7 days to 3 months after (p <0.001) and after 3 months it was lower by 10.1% compared to pre-ESWL values (p <0.001). uNGAL level after 12 h was significantly negatively associated with eGFR, 12 h, 7 days and 3 months after the ESWL. The sensitivity of uNGAL 12 h after ESWL was 60.6%; its specificity was 75.0%, with a positive predictive value of 74.0% and negative predictive value of 61.7%. Conclusions uNGAL appears to be a useful biomarker for the assessment and prediction of AKI. It was noticed that uNGAL had the highest predictive value 12 h after the ESWL treatment.