How has financial globalisation changed the nature of external vulnerability of emerging economies? To answer this question, we first present an overview of the changes in international capital flows and cross-border stocks involving emerging economies from the 1970s to the COVID-19 crisis, and then identify relevant recent shifts in financial globalisation. We link the concepts of financialisation, subordinated financial integration and currency hierarchy, extending the latter to consider the most recent features of financial globalisation. To better understand the metamorphosis of these economies’ vulnerabilities, we deploy a stylised balance sheet analysis. We find the occurrence of the phenomenon of ‘original sin’ during financial internationalisation, while in more recent times of financial globalisation the diversification of financial flows and investors, and the increase of securities denominated in domestic currency have created additional channels of vulnerability, labelled as ‘original sin redux’. We call for capital account regulation targeting these new complex vulnerabilities.View less
Turkey, as a developing country, is designing and performing massive construction projects around Istanbul. Beginning from the 1960s, rapid urbanization has been taking place due to industrialization, which brings an increase in the population. Yet, construction projects have been accelerated especially during the last decade, and many new projects are scheduled to be completed in a short time. Ground-based observations are generally carried out to monitor the deformations within construction sites, especially through geometric levelling, and GNSS techniques. However, in most cases, these monitoring measurements are only scheduled within the period of the construction process, and ensuing deformations are usually not considered. In addition to these techniques, the space-based interferometric technique can also be used to define the line of sight surface displacements with high accuracy, using the phase difference between image result for synthetic aperture radar images. In particular, Persistent Scatter Interferometry is one of the interferometric methods that are capable of defining the two-dimensional (vertical and horizontal) deformation for the desired epoch with a high temporal resolution. Thus it can be used as a complementary method for monitoring ground deformations, where the measurement is made by ground-based observations. In this study, the deforming areas related to underground metro construction are investigated through significant displacements between 2015 and 2018 of Sentinel-1 space-borne SAR data using the PSI technique. These results are validated by comparison with available levelling data corresponding to the new metro line.View less
Background: Pembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (≥50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit.
Methods: In this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated.
Results: A total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRASG12C group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRASother and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRASG12C/TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRASother/TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02).
Conclusions: A comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab.View less
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.View less
This study introduces and investigates the validity of a brief scale measuring a challenged sense of belonging. The sense of belonging as well as challenges to this sense are important, albeit neglected aspects of social integration and of significance to migration and refugee studies as well as to virtually all other social science contexts. Assessing a challenged or eroded sense of belonging provides important insights into how individuals relate to their environment and whether they feel socially connected or disconnected from it. The construct goes beyond national or cultural identity, instead emphasizing the dynamic processes of emotional attachment. Reviewing the substantial theoretical literature on belonging, we identify four of its key elements: connection, participation, identification, and congruence. Drawing on existing measurement instruments, we propose a brief Challenged Sense of Belonging Scale (CSBS) that addresses each of the four elements and investigate its validity in a unique, multi-lingual random sample of 3783 adult refugees in Germany from various national and cultural backgrounds. We provide evidence for the scale’s validity separately for three main survey languages (English, Arabic, Farsi/Dari) using confirmatory factor analysis, a test of measurement invariance, item test and rest correlations, and correlation analysis to explore convergent validity. Our findings suggest that the scale is a suitable instrument for the assessment of a challenged sense of belonging in a heterogeneous population of refugees.View less
President Trump has created turmoil in the transatlantic relationship. Biden has taken a conciliatory tone towards allies and promised to return the US to multilateral cooperation as president. But the transatlantic relationship will never return to its heyday. Three long-term trends will shape the future of US foreign policy and the transatlantic relationship: the global shift in the distribution of power, and especially what the US-China rivalry means for Europe; the US’ ambivalence towards multilateralism and why it will likely endure; and changing domestic coalitions within the US that might be a harbinger of a foreign policy revolution.View less
We investigated how patients with social anxiety disorder (SAD) and patients with borderline personality disorder (BPD) process an increase in the frequency of social interaction. We used an EEG-compatible version of the online ball-tossing game Cyberball to induce an increase in the frequency of social interaction. In the first condition, each player received the ball equally often (inclusion: 33% ball reception). In the following condition, the frequency of the ball reception was increased (overinclusion: 45% ball reception). The main outcome variable was the event-related potential P2, an indicator for social reward processing. Moreover, positive emotions were assessed. Twenty-eight patients with SAD, 29 patients with BPD and 28 healthy controls (HCs) participated. As expected, HCs and patients with BPD, but not patients with SAD, showed an increase in the P2 amplitude from the inclusion to the overinclusion condition. Contrary to our expectations, positive emotions did not change from the inclusion to the overinclusion condition. EEG results provide preliminary evidence that patients with BPD and HCs, but not patients with SAD, process an increase in the frequency of social interaction as rewarding.View less
Influenza A viruses contain two S-acylated proteins, the ion channel M2 and the glycoprotein hemagglutinin (HA). Acylation of the latter is essential for virus replication. Here we analysed the expression of each of the 23 members of the family of ZDHHC acyltransferases in human airway cells, the site of virus replication. RT-PCR revealed that every ZDHHC acyltransferase (except ZDHHC19) is expressed in A549 and Calu cells. Interestingly, expression of one ZDHHC, ZDHHC22, is upregulated in virus-infected cells; this effect is more pronounced after infection with an avian compared to a human virus strain. The viral protein NS1 triggers ZDHHC22 expression in transfected cells, whereas recombinant viruses lacking a functional NS1 gene did not cause ZDHHC22 upregulation. CRISPR/Cas9 technology was then used to knock-out the ZDHHC22 gene in A549 cells. However, acylation of M2 and HA was not reduced, as analysed for intracellular HA and M2 and the stoichiometry of S-acylation of HA incorporated into virus particles did not change according to MALDI-TOF mass spectrometry analysis. Comparative mass spectrometry of palmitoylated proteins in wt and Delta ZDHHC22 cells identified 25 potential substrates of ZDHHC22 which might be involved in virus replication.View less
Two potentially tripodal ligands, tris(1-phenyl-1H-1,2,3-triazol-4-yl)phosphine oxide (OP((1,2,3)Tz(1-Ph))(3)) and tris(1-benzyl-1H-1,2,3-triazol-4-yl)phosphine oxide (OP((1,2,3)Tz(1-benz))(3)), were used in reactions with [Re(CO)(5)Br] and (NEt4)(2)[Tc(CO)(3)Cl-3]. While the formation of rhenium complexes with bidentate and tridentate coordinated phosphine oxides was observed, for technetium only cationic complexes with tripodal coordinated OP((1,2,3)Tz(1-R)) ligands were isolated. The products have been characterized spectroscopically and by single crystal X-ray diffraction.View less
Aims: We aimed to elucidate whether the DNA extraction kit and bacteria therein affect the characterization of bacterial communities associated with butterfly samples harbouring different bacterial abundancies.
Methods and Results: We analysed bacteria associated with eggs of Pieris brassicae and with adults of this butterfly, which were either untreated or treated with antibiotics (ABs). Three DNA extraction kits were used. Regardless of the extraction kit used, PCR amplification of the bacterial 16S rRNA gene detected very low bacterial presence in eggs and AB‐treated butterflies. In untreated butterflies, bacterial signal intensity varied according to the kit and primers used. Sequencing (MiSeq) of the bacterial communities in untreated and AB‐treated butterflies revealed a low alpha diversity in untreated butterflies because of the dominance of few bacteria genera, which were detectable regardless of the kit. However, a significantly greater alpha diversity was found in AB‐treated butterflies, evidencing a true bias of the results due to bacterial contaminants in the kit.
Conclusions: The so‐called ‘kitome’ can impact the profiling of Lepidoptera‐associated bacteria in samples with low bacterial biomass.
Significance and Impact of the Study: Our study highlights the necessity of method testing and analysis of negative controls when investigating Lepidoptera‐associated bacterial communities.View less
Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor.View less
Die Eindämmung der Corona-Pandemie stellt Politik und insbesondere Regierungen vor immense Herausforderungen. Wie zufrieden ist die deutsche Bevölkerung mit dem Krisenmanagement unter dem Eindruck massiver Einschnitte in das wirtschaftliche, soziale und kulturelle Leben? In unserer repräsentativen Längsschnittbefragung stellt die Bevölkerung den politischen Akteuren kein gutes Zeugnis aus. Fast die Hälfte der Befragten sind im März 2021 unzufrieden mit dem Krisenmanagement und ein Fünftel sogar "total unzufrieden". Ein Blick in verschiedene Bevölkerungsgruppen zeigt, dass gerade Wähler*innen der AfD, der FDP und der Linken unzufrieden sind, während Wähler*innen von CDU/CSU das Krisenmanagement positiver sehen. Auch Befragte ohne Fachhochschulreife und Menschen aus den neuen Bundesländern bewerteten das Handeln der Politik weniger positiv. Zudem nahm die Zufriedenheit von Dezember 2020 zu März 2021 deutlich ab - gerade bei älteren Befragten. Insgesamt zeigt sich, dass die Ablehnung der Maßnahmen zur Eindämmung häufig mit Unzufriedenheit einhergehen, aber Unterstützer*innen der Maßnahmen nicht unbedingt zufriedener mit dem Krisenmanagement der Regierung sind.View less
Two n×n Latin squares L1,L2 are said to be orthogonal if, for every ordered pair (x, y) of symbols, there are coordinates (i, j) such that L1(i,j)=x and L2(i,j)=y. A k-MOLS is a sequence of k pairwise-orthogonal Latin squares, and the existence and enumeration of these objects has attracted a great deal of attention. Recent work of Keevash and Luria provides, for all fixed k, log-asymptotically tight bounds on the number of k-MOLS. To study the situation when k grows with n, we bound the number of ways a k-MOLS can be extended to a (k+1)-MOLS. These bounds are again tight for constant k, and allow us to deduce upper bounds on the total number of k-MOLS for all k. These bounds are close to tight even for k linear in n, and readily generalise to the broader class of gerechte designs, which include Sudoku squares.View less
We study the following separation problem: Given a collection of pairwise disjoint coloured objects in the plane with k different colours, compute a shortest “fence” F, i.e., a union of curves of minimum total length, that separates every pair of objects of different colours. Two objects are separated if F contains a simple closed curve that has one object in the interior and the other in the exterior. We refer to the problem as geometric k-cut, as it is a geometric analog to the well-studied multicut problem on graphs. We first give an O(n4log3n)-time algorithm that computes an optimal fence for the case where the input consists of polygons of two colours with n corners in total. We then show that the problem is NP-hard for the case of three colours. Finally, we give a randomised 4/3⋅1.2965-approximation algorithm for polygons and any number of colours.View less