bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper)
Authors: Wiendl Heinz , Gold Ralf , Berger Thomas , Derfuss Tobias , Linker Ralf , Mäurer Mathias , Stangel Martin , Aktas Orhan , Baum Karl , Berghoff Martin , Bittner Stefan , Chan Andrew , Czaplinski Adam , Deisenhammer Florian , Di Pauli Franziska , Du Pasquier Renaud , Enzinger Christian , Fertl Elisabeth , Gass Achim , Gehring Klaus , Gobbi Claudio , Goebels Norbert , Guger Michael , Haghikia Aiden , Hartung Hans‑Peter , Heidenreich Fedor , Hoffmann Olaf , Hunter Zoë R. , Kallmann Boris , Kleinschnitz Christoph , Klotz Luisa , Leussink Verena , Leutmezer Fritz , Limmroth Volker , Lünemann Jan D. , Lutterotti Andreas , Meuth Sven G. , Meyding-Lamadé Uta , Platten Michael , Rieckmann Peter , Schmidt Stephan , Tumani Hayrettin , Weber Martin S. , Weber Frank , Zettl Uwe K. , Ziemssen Tjalf , Zipp Frauke ,   die Multiple Sklerose Therapie Konsensus Gruppe (MSTKG)
Published: July 2021

Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.
Stellenwert des 1,5-T-MR-Linearbeschleunigers für die primäre Therapie des Prostatakarzinoms
Authors: Wegener Daniel , Zips Daniel , Gani Cihan , Boeke Simon , Nikolaou Konstantin , Othman Ahmed E. , Almansour Haidara , Paulsen Frank , Müller Arndt-Christian
Published: July 2021

Hintergrund

Der potenzielle Nutzen des verbesserten Weichteilkontrastes von MR-Sequenzen gegenüber der Computertomographie (CT) für die Radiotherapie des Prostatakarzinoms ist bekannt und führt zu konsistenteren und kleineren Zielvolumina sowie verbesserter Risikoorganschonung. Hybridgeräte aus Magnetresonanztomographie (MRT) und Linearbeschleuniger (MR-Linac) stellen eine neue vielversprechende Erweiterung der radioonkologischen Therapieoptionen dar.

Material und Methoden

Dieser Artikel gibt eine Übersicht über bisherige Erfahrungen, Indikationen, Vorteile und Herausforderungen für die Radiotherapie des primären Prostatakarzinoms mit dem 1,5-T-MR-Linac.

Ergebnisse

Alle strahlentherapeutischen Therapieindikationen für das primäre Prostatakarzinom können mit dem 1,5-T-MR-Linac abgedeckt werden. Die potenziellen Vorteile umfassen die tägliche MR-basierte Lagekontrolle in Bestrahlungsposition und die Möglichkeit der täglichen Echtzeitanpassung des Bestrahlungsplans an die aktuelle Anatomie der Beckenorgane (adaptive Strahlentherapie). Zusätzlich werden am 1,5-T-MR-Linac funktionelle MRT-Sequenzen für individuelles Response-Assessment für die Therapieanpassung untersucht. Dadurch soll das therapeutische Fenster weiter optimiert werden. Herausforderungen stellen u. a. die technische Komplexität und die Dauer der Behandlungssitzung dar.

Schlussfolgerung

Der 1,5-T-MR-Linac erweitert das radioonkologische Spektrum in der Therapie des Prostatakarzinoms und bietet Vorteile durch tagesaktuelle MRT-basierte Zielvolumendefinition und Planadaptation. Weitere klinische Untersuchungen sind notwendig, um die Patienten zu identifizieren, die von der Behandlung am MR-Linac gegenüber anderen strahlentherapeutischen Methoden besonders profitieren.
Trajectories of antidepressant use and characteristics associated with trajectory groups among young refugees and their Swedish-born peers with diagnosed common mental disorders—findings from the REMAIN study
Authors: Rahman S. , Filatova S. , Chen L. , Björkenstam E. , Taipale H. , Mittendorfer-Rutz E.
Published: July 2021

Purpose

This study aimed to (1) identify the trajectories of prescribed antidepressants in refugee youth and matched Swedish-born peers diagnosed with common mental disorder (CMD) and (2) characterize the trajectories according to sociodemographic and medical factors.

Methods

The study population comprised 2,198 refugees and 12,199 Swedish-born individuals with both Swedish-born parents, aged 16–25 years in 2011, residing in Sweden and treated in specialised healthcare for CMD 2009–11. Group-based trajectory modelling was used to identify different trajectory groups of antidepressant use-based on annual defined daily dosages (DDDs). Multinomial logistic regression was applied to investigate the association of sociodemographic and medical characteristics with the identified trajectories. Nagelkerke pseudo-R2 values were estimated to evaluate the strength of these associations.

Results

Four trajectory groups of antidepressant use among young refugees were identified with following proportions and DDD levels in 2011: ‘low constant’ (88%, < 100), ‘low increasing’ (2%, ≈710), ‘medium decreasing’ (8%, ≈170) and ‘high increasing’ (2%, ≈860). Similar trajectories, however, with different proportions were identified in Swedish-born: 67%, 7%, 21% and 5%, respectively. The most influential factors discriminating the trajectory groups among refugees were ‘duration of stay in Sweden’ (R2 = 0.013), comorbid ‘other mental disorders’ (R2 = 0.009) and ‘disability pension’ (R2 = 0.007), while ‘disability pension’ (R2 = 0.017), comorbid ‘other mental disorders’ (R2 = 0.008) and ‘educational level’ (R2 = 0.008) were the most important determinants discriminating trajectory groups among Swedish-born youth.

Conclusion

The lower use of antidepressants in refugees with CMDs compared to their Swedish-born counterparts warrants health literacy programs for refugees and training in transcultural psychiatry for healthcare professionals.
Approximating solution spaces as a product of polygons
Authors: Harbrecht Helmut , Tröndle Dennis , Zimmermann Markus
Published: July 2021

Solution spaces are regions of good designs in a potentially high-dimensional design space. Good designs satisfy by definition all requirements that are imposed on them as mathematical constraints. In previous work, the complete solution space was approximated by a hyper-rectangle, i.e., the Cartesian product of permissible intervals for design variables. These intervals serve as independent target regions for distributed and separated design work. For a better approximation, i.e., a larger resulting solution space, this article proposes to compute the Cartesian product of two-dimensional regions, so-called 2d-spaces, that are enclosed by polygons. 2d-spaces serve as target regions for pairs of variables and are independent of other 2d-spaces. A numerical algorithm for non-linear problems is presented that is based on iterative Monte Carlo sampling.
The geography of COVID-19 in Sweden
Authors: Florida Richard , Mellander Charlotta
Published: July 2021

This paper examines the geographic factors that are associated with the spread of COVID-19 during the first wave in Sweden. We focus particularly on the role of place-based factors versus factors associated with the spread or diffusion of COVID-19 across places. Sweden is a useful case study to examine the interplay of these factors because it did not impose mandatory lockdowns and because there were essentially no regional differences in the pandemic policies or strategies during the first wave of COVID-19. We examine the role of place-based factors like density, age structures and different socioeconomic factors on the geographic variation of COVID-19 cases and on deaths, across both municipalities and neighborhoods. Our findings show that factors associated with diffusion matter more than place-based factors in the geographic incidence of COVID-19 in Sweden. The most significant factor of all is proximity to places with higher levels of infections. COVID-19 is also higher in places that were hit earliest in the outbreak. Of place-based factors, the geographic variation in COVID-19 is most significantly related to the presence of high-risk nursing homes, and only modestly associated with factors like density, population size, income and other socioeconomic characteristics of places.
A generalization of Milnor’s formula
Authors: Zach Matthias
Published: July 2021

The Milnor number $$\mu _f$$

μ
f

of a holomorphic function $$f :({\mathbb {C}}^n,0) \rightarrow ({\mathbb {C}},0)$$

f
:

(

C

n

,
0
)

→

(
C
,
0
)

with an isolated singularity has several different characterizations as, for example: 1) the number of critical points in a morsification of f, 2) the middle Betti number of its Milnor fiber $$M_f$$

M
f

, 3) the degree of the differential $${\text {d}}f$$

d
f

at the origin, and 4) the length of an analytic algebra due to Milnor’s formula $$\mu _f = \dim _{\mathbb {C}}{\mathcal {O}}_n/{\text {Jac}}(f)$$

μ
f

=

dim
C

O
n

/
Jac

(
f
)

. Let $$(X,0) \subset ({\mathbb {C}}^n,0)$$

(
X
,
0
)

⊂

(

C

n

,
0
)

be an arbitrarily singular reduced analytic space, endowed with its canonical Whitney stratification and let $$f :({\mathbb {C}}^n,0) \rightarrow ({\mathbb {C}},0)$$

f
:

(

C

n

,
0
)

→

(
C
,
0
)

be a holomorphic function whose restriction f|(X, 0) has an isolated singularity in the stratified sense. For each stratum $${\mathscr {S}}_\alpha $$

S
α

let $$\mu _f(\alpha ;X,0)$$

μ
f

(
α
;
X
,
0
)

be the number of critical points on $${\mathscr {S}}_\alpha $$

S
α

in a morsification of f|(X, 0). We show that the numbers $$\mu _f(\alpha ;X,0)$$

μ
f

(
α
;
X
,
0
)

generalize the classical Milnor number in all of the four characterizations above. To this end, we describe a homology decomposition of the Milnor fiber $$M_{f|(X,0)}$$

M

f
|
(
X
,
0
)

in terms of the $$\mu _f(\alpha ;X,0)$$

μ
f

(
α
;
X
,
0
)

and introduce a new homological index which computes these numbers directly as a holomorphic Euler characteristic. We furthermore give an algorithm for this computation when the closure of the stratum is a hypersurface.
Species-specific isotope dilution analysis of monomethylmercury in sediment using GC/ICP-ToF-MS and comparison with ICP-Q-MS and ICP-SF-MS
Authors: Faßbender Sebastian , von der Au Marcus , Koenig Maren , Pelzer Jürgen , Piechotta Christian , Vogl Jochen , Meermann Björn
Published: July 2021

A recently introduced inductively coupled plasma-time-of-flight-mass spectrometer (ICP-ToF-MS) shows enhanced sensitivity compared to previous developments and superior isotope ratio precision compared to other ToF and commonly used single-collector ICP-MS instruments. Following this fact, an improvement for isotope dilution ICP-MS using the new instrumentation has been reported. This study aimed at investigating whether this improvement also meets the requirements of species-specific isotope dilution using GC/ICP-MS, where short transient signals are recorded. The results of the analysis of monomethylmercury (MMHg) of a sediment reference material show that isotope ratio precision of ICP-MS instruments equipped with quadrupole, sector-field, and time-of-flight mass analyzers is similar within a broad range of peak signal-to-noise ratio when analyzing one isotopic system. The procedural limit of quantification (LOQ) for MMHg, expressed as mass fraction of Hg being present as MMHg, w(Hg)MMHg, was similar as well for all investigated instruments and ranged between 0.003 and 0.016 μg/kg. Due to the simultaneous detection capability, the ICP-ToF-MS might, however, be more favorable when several isotopic systems are analyzed within one measurement. In a case study, the GC/ICP-ToF-MS coupling was applied for analysis of MMHg in sediments of Finow Canal, a historic German canal heavily polluted with mercury. Mass fractions between 0.180 and 41 μg/kg (w(Hg)MMHg) for MMHg, and 0.056 and 126 mg/kg (w(Hg)total) for total mercury were found in sediment samples taken from the canal upstream and downstream of a former chemical plant.

Graphical abstract
The Na/K-ATPase Signaling and SGLT2 Inhibitor-Mediated Cardiorenal Protection: A Crossed Road?
Authors: Liu Jiang , Tian Jiang , Sodhi Komal , Shapiro Joseph I.
Published: July 2021

In different large-scale clinic outcome trials, sodium (Na+)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na+gradient to drive other Na+-dependent transporters, the possible role of the sodium–potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored.

Graphic Abstract
Spontaneous intracranial hypotension: diagnostic and therapeutic workup
Authors: Luetzen Niklas , Dovi-Akue Philippe , Fung Christian , Beck Juergen , Urbach Horst
Published: July 2021

Spontaneous intracranial hypotension (SIH) is an orthostatic headache syndrome with typical MRI findings among which engorgement of the venous sinuses, pachymeningeal enhancement, and effacement of the suprasellar cistern have the highest diagnostic sensitivity. SIH is in almost all cases caused by spinal CSF leaks. Spinal MRI scans showing so-called spinal longitudinal extradural fluid (SLEC) are suggestive of ventral dural tears (type 1 leak) which are located with prone dynamic (digital subtraction) myelography. As around half of the ventral dural tears are located in the upper thoracic spine, additional prone dynamic CT myelography is often needed. Leaking nerve root sleeves typically associated with meningeal diverticulae (type 2 leaks) and CSF-venous fistulas (type 3 leaks) are proven via lateral decubitus dynamic digital subtraction or CT myelography: type 2 leaks are SLEC-positive if the tear is proximal and SLEC-negative if it is distal, and type 3 leaks are always SLEC-negative. Although 30–70% of SIH patients show marked improvement following epidural blood patches applied via various techniques definite cure mostly requires surgical closure of ventral dural tears and surgical ligations of leaking nerve root sleeves associated with meningeal diverticulae or CSF-venous fistulas. For the latter, transvenous embolization with liquid embolic agents via the azygos vein system is a novel and valuable therapeutic alternative.
Control of Magnaporthe oryzae and Rice Growth Promotion by Bacillus subtilis JN005
Authors: Zhu Huajun , Zhou Hu , Ren Zuohua , Liu Erming
Published: July 2021

It is quite important to develop the microorganism resources with biocontrol capacity for rice blast. This study evaluated Bacillus subtilis JN005 for growth promotion and biocontrol efficacy against Magnaporthe oryzae. Results showed that rice seeds treated with 1 × 107 cfu/mL suspension of B. subtilis JN005 had 16% germination energy, 14% germination rate, 15% germination index, and 270% vigor index compared to those treated with sterile water (control). In pot experiments, the JN005 strain-treated rice plants exhibited notable increase in plant height, root length, stem circumference, and fresh weight, as well as higher concentration of chlorophyll a, chlorophyll b, and total chlorophyll in rice leaves. Rice leaves inoculated with the JN005 strain resulted in increased activities of defense-related enzymes, including peroxidase (POD), phenylalanine ammonialyase (PAL), superoxide dismutase (SOD), and catalase (CAT) compared to the water and the M. oryzae-inoculated treatments. In vitro inoculated rice leaves with 1 × 107 cfu/mL bacterial suspension compared to sterile water or control treatment exhibited lower disease incidence in the curative and preventive groups by 79% and 76%, respectively. Field experiment showed that after spraying with 1 × 107 cfu/mL bacterial suspension, efficacy rates on controlling rice blast on plants were (56.82 ± 1.12)% and (58.39 ± 3.05)% at seedling and maturity stages, respectively, and that rice production yield was (524.40 ± 17.88) g/m2. Therefore, B. subtilis JN005 could be a promising biological control agent for rice blast, thereby warranting further investigation of its efficacy.
Strong Cliques in Claw-Free Graphs
Authors: Dębski Michał , Śleszyńska-Nowak Małgorzata
Published: July 2021

For a graph G, $$L(G)^2$$

L

(
G
)

2

is the square of the line graph of G – that is, vertices of $$L(G)^2$$

L

(
G
)

2

are edges of G and two edges $$e,f\in E(G)$$

e
,
f
∈
E
(
G
)

are adjacent in $$L(G)^2$$

L

(
G
)

2

if at least one vertex of e is adjacent to a vertex of f and $$e\ne f$$

e
≠
f

. The strong chromatic index of G, denoted by $$s'(G)$$

s
′

(
G
)

, is the chromatic number of $$L(G)^2$$

L

(
G
)

2

. A strong clique in G is a clique in $$L(G)^2$$

L

(
G
)

2

. Finding a bound for the maximum size of a strong clique in a graph with given maximum degree is a problem connected to a famous conjecture of Erdős and Nešetřil concerning strong chromatic index of graphs. In this note we prove that a size of a strong clique in a claw-free graph with maximum degree $$\varDelta $$
Δ
is at most $$\varDelta ^2 + \frac{1}{2}\varDelta $$

Δ
2

+

1
2

Δ

. This result improves the only known result $$1.125\varDelta ^2+\varDelta $$

1.125

Δ
2

+
Δ

, which is a bound for the strong chromatic index of claw-free graphs.
The impact of a needs-oriented dental prophylaxis program on bacteremia after toothbrushing and systemic inflammation in children, adolescents, and young adults with chronic kidney disease
Authors: Höfer Karolin , Turnowsky Anna , Ehren Rasmus , Taylan Christina , Plum Georg , Witte Hanna , Noack Michael J. , Weber Lutz T.
Published: July 2021

Background

Chronic kidney disease (CKD) still leads to high mortality rates, mainly due to cardiovascular disease. One important influencing factor is persisting low-grade chronic inflammation partly maintained by gingivitis that favors transient bacteremia during daily activities such as toothbrushing.

Methods

To examine whether intensive dental prophylaxis can restore oral health, reduce the prevalence of bacteremia and degree of systemic inflammation indicated by CRP levels, we conducted this pilot study examining 30 CKD patients aged 6–26 years, 15 receiving intensive prophylaxis (IP), 15 receiving treatment as usual (TAU) serving as control group. There were three appointments for examination, each 10 ± 1 weeks apart (at baseline, after intervention periods one and two, when TAU also received IP, and the IP group stopped prophylaxis).

Results

The gingival index (GI) in the IP group decreased by 90% (GI 0.09; p=0.001), resulting in almost healthy gingiva. There was no significant change in CRP or prevalence of bacteremia. General prevalence of bacteremia after toothbrushing was 9.5% affecting 7 (26%) of the participants. In three participants, bacteremia dissolved after IP, in one after TAU. Two patients developed bacteremia ≥ 10 weeks after ending IP. We identified eight different bacterial species.

Conclusions

We were able to show that IP can effectively treat gingivitis. It might be a promising approach to reduce systemic inflammation and subsequently lower premature cardiovascular disease, despite the lack of statistical significance. Future research requires a larger patient cohort to enable matched treatment groups with long-term follow-up and molecular detection methods for bacteremia.

Graphical abstract
The lived body (Der Leib) as a diagnostic and therapeutic instrument in general practice
Authors: Langewitz Wolf Axel
Published: July 2021

Based on vignettes from clinical cases, supervision and Balint groups this article presents a neo-phenomenological perspective on the lived experience of healthcare professionals in interactions with patients and relatives. Specifically, the familiar phenomenon of “something in the air” between two persons will be analyzed.

Constellations and situations are presented as fundamental and generic (ontological) categories that can be differentiated to understand the details and the whole (die Gestalt) of an interaction.

The term atmosphere is introduced to investigate the material carrier of something that “colors the air” between healthcare provider and patient.

The neo-phenomenological taxonomy of the lived body (der Leib) is used to describe the recipient structure of atmospheric mood.

Finally, the potential of these concepts for a more comprehensive diagnosis and for therapeutic use in general practice will be elucidated.
Targeted self-management limits fatigue for women undergoing radiotherapy for early breast cancer: results from the ACTIVE randomised feasibility trial
Authors: Courtier Nick , Armes Jo , Smith Andrew , Radley Lesley , Hopkinson Jane B.
Published: July 2021

Purpose

The ACTIVE intervention uses a novel fatigue propensity tool to target a behavioural fatigue self-management programme for women undergoing radiotherapy for early breast cancer. We assess feasibility and outcomes for ACTIVE.

Methods

Mixed methods comprised a randomised feasibility trial with qualitative process evaluation and a nested fatigue risk substudy. Participants at a higher risk of fatigue were allocated 2:1 to behavioural intervention or information alone. Participants at a lower risk of fatigue entered the fatigue risk substudy. Feasibility was assessed by rates of eligibility, recruitment, retention and adherence. Qualitative interviews explored acceptability of the intervention and trial processes. Measures of fatigue, anxiety, depression, quality of life and self-efficacy were self-reported before, during and 10 days, 3 weeks and 6 months after radiotherapy. Pre-treatment fatigue risk score and post-treatment fatigue were correlated.

Results

Fifty percent (n = 75) of eligible patients were recruited with 33 higher risk participants randomised to the trial and 42 entering the fatigue risk score substudy. Trial design and methods were feasible and acceptable with 91% of participants completing all measures according to protocol. Fatigue was clinically-significantly lower in the intervention group during, and in the weeks after, treatment compared to the control: all secondary measures favoured the intervention group. Positive group differences were not maintained at 6 months.

Conclusion

Our targeted approach to fatigue self-management is feasible and acceptable within the early breast cancer pathway. Multiple benefits were reported by patients who received the intervention, which is worthy of further investigation.

Trial registration

ISRCTN 10303368. Registered August 2017. Health and Care Research Wales Clinical Trial Portfolio Registration 31419.
Commentary: Quality nutrition care is integral to the Oncology Care Model
Authors: Arensberg Mary Beth , Besecker Beth , Weldishofer Laura , Drawert Susan
Published: July 2021

The Oncology Care Model (OCM) is a US Centers for Medicare & Medicaid Services (CMS) specialty model implemented in 2016, to provide higher quality, more highly coordinated oncology care at the same or lower costs. Under the OCM, oncology clinics enter into payment arrangements that include financial and performance accountability for patients receiving chemotherapy treatment. In addition, OCM clinics commit to providing enhanced services to Medicare beneficiaries, including care coordination, navigation, and following national treatment guidelines. Nutrition is a component of best-practice cancer care, yet it may not be addressed by OCM providers even though up to 80% of patients with cancer develop malnutrition and poor nutrition has a profound impact on cancer treatment and survivorship. Only about half of US ambulatory oncology settings screen for malnutrition, registered dietitian nutritionists (RDNs) are not routinely employed by oncology clinics, and the medical nutrition therapy they provide is often not reimbursed. Thus, adequate nutrition care in US oncology clinics remains a gap area. Some oncology clinics are addressing this gap through implementation of nutrition-focused quality improvement programs (QIPs) but many are not. What is needed is a change of perspective. This paper outlines how and why quality nutrition care is integral to the OCM and can benefit patient health and provider outcomes.
Performance of daily satellite-based rainfall in groundwater basin of Merapi Aquifer System, Yogyakarta
Authors: Rahmawati Novi , Rahayu Kisworo , Yuliasari Sukma Tri
Published: July 2021

Evaluation of the performance of daily satellite-based rainfall (CMORPH, CHIRPS, GPM IMERG, and TRMM) was done to obtain applicable satellite rainfall estimates in the groundwater basin of the Merapi Aquifer System (MAS). Performance of satellite data was assessed by applying descriptive statistics, categorical statistics, and bias decomposition on the basis of daily rainfall intensity classification. This classification is possible to measure the performance of daily satellite-based rainfall in much detail. CM (CMORPH) has larger underestimation compared to other satellite-based rainfall assessments. This satellite-based rainfall also mostly has the largest RMSE, while CHR (CHIRPS) has the lowest. CM has a good performance to detect no rain, while IMR (GPM IMERG) has the worst performance. IMR and CHR have a good performance to detect light and moderate rain. Both of them have larger H frequencies and lower MB values compared to other satellite products. CHR mostly has a good performance compared to TR (TRMM), especially on wet periods. CM, IMR, and TR mostly have a good performance on dry periods, while CHR on wet periods. CM mostly has the largest MB and lowest AHB values. CM and CHR have better accuracy to estimate rain amount compared to IMR and TR. All in all, all 4 satellite-based rainfall assessments have large discrepancy compared with rain gauge data along mountain range where orographic rainfall usually occurs in wet periods. Hence, it is recommended to evaluate satellite-based rainfall with time series of streamflow simulation in hydrological modeling framework by merging rain gauge data with more than one satellite-based rainfall than to merge both IMR and TR together.
POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients
Authors: Di Donato Ilaria , Gallo Antonio , Ricca Ivana , Fini Nicola , Silvestri Gabriella , Gurrieri Fiorella , Cirillo Mario , Cerase Alfonso , Natale Gemma , Matrone Federica , Riso Vittorio , Melone Mariarosa Anna Beatrice , Tessa Alessandra , De Michele Giovanna , Federico Antonio , Filla Alessandro , Dotti Maria Teresa , Santorelli Filippo Maria
Published: July 2021

Mutations inPOLR3Aare characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation inPOLR3A. Here, we present 10 patients from 8 unrelated families withPOLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a “pure” cerebellar phenotype, and one a “pure” spastic presentation. The non-neurological findings typically associated withPOLR3Amutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. ThePOLR3Amutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14–18. Interestingly, this patient had the most “complex” presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onsetPOLR3A-related disorders, and therefore further expand the phenotype.
The road to success of coagulase-negative staphylococci: clinical significance of small colony variants and their pathogenic role in persistent infections
Authors: Bogut Agnieszka , Magryś Agnieszka
Published: July 2021

Bacterial small colony variants represent an important aspect of bacterial variability. They are naturally occurring microbial subpopulations with distinctive phenotypic and pathogenic traits, reported for many clinically important bacteria. In clinical terms, SCVs tend to be associated with persistence in host cells and tissues and are less susceptible to antibiotics than their wild-type (WT) counterparts. The increased tendency of SCVs to reside intracellularly where they are protected against the host immune responses and antimicrobial drugs is one of the crucial aspects linking SCVs to recurrent or chronic infections, which are difficult to treat. An important aspect of the SCV ability to persist in the host is the quiescent metabolic state, reduced immune response and expression a changed pattern of virulence factors, including a reduced expression of exotoxins and an increased expression of adhesins facilitating host cell uptake. The purpose of this review is to describe in greater detail the currently available data regarding CoNS SCV and, in particular, their clinical significance and possible mechanisms by which SCVs contribute to the pathogenesis of the chronic infections. It should be emphasized that in spite of an increasing clinical significance of this group of staphylococci, the number of studies unraveling the mechanisms of CoNS SCVs formation and their impact on the course of the infectious process is still scarce, lagging behind the studies on S. aureus SCVs.
Stackelberg pricing games with congestion effects
Authors: Harks Tobias , Schedel Anja
Published: July 2021

We study a Stackelberg game with multiple leaders and a continuum of followers that are coupled via congestion effects. The followers’ problem constitutes a nonatomic congestion game, where a population of infinitesimal players is given and each player chooses a resource. Each resource has a linear cost function which depends on the congestion of this resource. The leaders of the Stackelberg game each control a resource and determine a price per unit as well as a service capacity for the resource influencing the slope of the linear congestion cost function. As our main result, we establish existence of pure-strategy Nash–Stackelberg equilibria for this multi-leader Stackelberg game. The existence result requires a completely new proof approach compared to previous approaches, since the leaders’ objective functions are discontinuous in our game. As a consequence, best responses of leaders do not always exist, and thus standard fixed-point arguments á la Kakutani (Duke Math J 8(3):457–458, 1941) are not directly applicable. We show that the game is C-secure (a concept introduced by Reny (Econometrica 67(5):1029–1056, 1999) and refined by McLennan et al. (Econometrica 79(5):1643–1664, 2011), which leads to the existence of an equilibrium. We furthermore show that the equilibrium is essentially unique, and analyze its efficiency compared to a social optimum. We prove that the worst-case quality is unbounded. For identical leaders, we derive a closed-form expression for the efficiency of the equilibrium.
Theory, methods, and operational results of the Young Women’s Health History Study: a study of young-onset breast cancer incidence in Black and White women
Authors: Velie Ellen M. , Marcus Lydia R. , Pathak Dorothy R. , Hamilton Ann S. , DiGaetano Ralph , Klinger Ron , Gollapudi Bibi , Houang Richard , Carnegie Nicole , Olson L. Karl , Allen Amani , Zhang Zhenzhen , Modjesk Denise , Norman Gwendolyn , Lucas Darek R. , Gupta Sapna , Rui Hallgeir , Schwartz Kendra
Published: July 2021

Purpose

The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case–control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results.

Methods

Cases were non-Hispanic Black (NHB) and White (NHW) women age 20–49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010–2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected.

Results

Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases.

Conclusions

Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.
Bayesian Estimation of Agent-Based Models via Adaptive Particle Markov Chain Monte Carlo
Authors: Lux Thomas
Published: July 2021

Over the last decade, agent-based models in economics have reached a state of maturity that brought the tasks of statistical inference and goodness-of-fit of such models on the agenda of the research community. While most available papers have pursued a frequentist approach adopting either likelihood-based algorithms or simulated moment estimators, here we explore Bayesian estimation using a Markov chain Monte Carlo approach (MCMC). One major problem in the design of MCMC estimators is finding a parametrization that leads to a reasonable acceptance probability for new draws from the proposal density. With agent-based models the appropriate choice of the proposal density and its parameters becomes even more complex since such models often require a numerical approximation of the likelihood. This brings in additional factors affecting the acceptance rate as it will also depend on the approximation error of the likelihood. In this paper, we take advantage of a number of recent innovations in MCMC: We combine Particle Filter Markov Chain Monte Carlo as proposed by Andrieu et al. (J R Stat Soc B 72(Part 3):269–342, 2010) with adaptive choice of the proposal distribution and delayed rejection in order to identify an appropriate design of the MCMC estimator. We illustrate the methodology using two well-known behavioral asset pricing models.
Dynamical Gibbs–non-Gibbs Transitions in the Curie–Weiss Potts Model in the Regime$$\beta <3$$
Authors: Külske Christof , Meißner Daniel
Published: July 2021

We consider the Curie–Weiss Potts model in zero external field under independent symmetric spin-flip dynamics. We investigate dynamical Gibbs–non-Gibbs transitions for a range of initial inverse temperatures $$\beta <3$$

β
<
3

, which covers the phase transition point $$\beta = 4\log 2$$

β
=
4
log
2

(Ellis and Wang in Stoch Process Appl 35(1):59–79, 1990). We show that finitely many types of trajectories of bad empirical measures appear, depending on the parameter $$\beta $$
β
, with a possibility of re-entrance into the Gibbsian regime, of which we provide a full description.
The Effect of Various Additions on the Oxidation Behavior of the γ/γ′ Ni-Based Alloy
Authors: Dąbek Jarosław , Prażuch Janusz , Migdalska Monika , Jawańska Monika , Ziąbka Magdalena , Wójcik-Bania Monika , Jedliński Jerzy
Published: July 2021

The oxidation behavior of four γ/γ′ Ni-based alloys: without additions, and containing: Hf (1.0 wt%), a combination of Hf and Y (0.3 wt% and 0.03 wt%, respectively), and a combination of Hf and Si (1.0 wt% and 1.0 wt%, respectively) was studied in air under isothermal (50 h) and thermal cycling (up to 2225 1-h cycles) conditions. Samples were characterized using SEM, EDX and XRD techniques. The results indicated that all the additions improved the oxidation resistance of the alloy but only in the case of materials containing the (Hf + Y) combination of additions was a long-term effect achieved. Substantial weight losses were observed on the other unmodified and (Hf + Si)-containing materials during thermal cycling after short exposure periods, while on material containing only additions of Hf, they occurred significantly later. Kinetic studies showed the highest oxidation rate in the case of the (Hf + Si)-containing alloys and the fastest initial oxidation, prior to the parabolic law-obeying stage, of alloy with Hf-additions, only. The results indicate the superior effect of simultaneous application of Hf and Y additions at levels not exceeding their solubility limits and that lowering its effectiveness Hf overdoping (1 wt%) cannot be effectively counteracted by the addition of 1% Si.
Affective shifts: mood, emotion and well-being
Authors: Mitchell Jonathan
Published: July 2021

It is a familiar feature of our affective psychology that our moods ‘crystalize’ into emotions, and that our emotions ‘diffuse’ into moods. Providing a detailed philosophical account of these affective shifts, as I will call them, is the central aim of this paper. Drawing on contemporary philosophy of emotion and mood, alongside distinctive ideas from the phenomenologically-inspired writer Robert Musil, a broadly ‘intentional’ and ‘evaluativist’ account will be defended. I argue that we do best to understand important features of these affective shifts–which I document across this paper–in terms of intentional and evaluative aspects of the respective states of moods and emotion. At same the time, the account is pitched at the phenomenological level, as dealing with affective shifts primarily in terms of moods and emotions as experiential states, with respect to which it feels-like-something to be undergoing the relevant affective experience. The paper also applies the intentional-evaluative model of affective shifts to anxiety in more detail, developing the idea that certain patterns of affective shift, particularly those that allow for a kind of ‘emotional release’, can contribute to a subject’s well-being.
Researchers working with city administrations: Reflecting on transdisciplinary collaboration under conditions of shared goals but different constraints
Authors: Home Robert , Bauer Nicole
Published: July 2021

Academics and city administrations generally agree that environmental management decisions should be science based, which suggests the value of collaboration between city officials and researchers. Such collaboration, termed “ecology with cities”, is an example of translational ecology that should integrate ecological and social sciences to inform decision-makers. However, there has been insufficient reflection on whether ecology with cities achieves the expected development of practical social-ecological knowledge for the common good. We addressed this gap by asking city officials and researchers, in Switzerland and with whom we have collaborated in the past, about their motivations for, and experiences with, transdisciplinary collaboration. The respondents reported largely overlapping goals and an awareness of the mutual benefits of accessing the skills and resources of the other group. However, the reflections also unearthed latent tensions related to insufficient mutual awareness of institutional boundaries and limitations. We conclude that researchers should try to include collaboration partners who have experience in translational ecology practice and should establish learning processes early in a collaboration. Building good working relationships with city administrations and establishing such processes would facilitate the creation of realistic mutual expectations in which institutional limitations are considered so that common goals of maintaining or improving the ecological quality of cities can be amicably reached.
Bie Jia Jian pill enhances the amelioration of bone mesenchymal stem cells on hepatocellular carcinoma progression
Authors: Jingjing Huang , Hongna Huang , Xiaojiao Wang , Yan Guo , Yuexue Zhong , Yueqiang Hu
Published: July 2021

Background

The therapeutic efficiency of Traditional Chinese Medicine (TCM) in suppressing the recurrence and metastasis of hepatocellular carcinoma (HCC) has been well proved.

Objective

The aim of this study is to investigate the role of Bie Jia Jian pill (BJJP) combined with bone mesenchymal stem cells (BMSCs) in HCC progression.

Methods

Flow cytometry was used to identify BMSCs isolated from BALB/c mice. The expressions of biomarkers and apoptosis rate of cancer stem cells (CSCs) enriched from Huh7 cells were also measured. The osteogenic differentiation and adipogenic differentiation ability of isolated BMSCs was determined by oil red O staining and Alizarin Red Staining. CSCs were used to establish the orthotopic HCC model. Histological changes in the liver tissues were examined by hematoxylin–eosin (H&E) staining and Van Gieson (VG) staining. The cell apoptotic rate in the cancer tissues was detected by TUNEL staining. The cell proliferation antigen Ki67 in the cancer tissues were detected by immunofluorescence assay and PCR, respectively. The levels of CSCs cellular surface markers (CD24, CD133 and EpCAM) and Wnt/β-catenin signal pathway related proteins were detected by PCR and western blot.

Results

Treatment of BJJP or BMSCs both improved the morphology induced by HCC and suppressed the differentiation ability of CSCs, as evidenced by down-regulated expressions of CD24, CD133, EpCAM and Ki67. The protective effect of BJJP or BMSCs in cancer tissues can be enhanced by the combination of BJJP and BMSCs. In addition to that, BJJP or BMSCs alone was found to increase the expression of miR-140 and promote cell apoptosis in CSCs, while down-regulation of miR-140 partially reversed the protective effect of BMSCs or BJJP + BMSCs on cancer tissues. BJJP + BMSCs treatment together also can down-regulate the expressions of Wnt3a and β-catenin.

Conclusions

These results proved the inhibitory role of BJJP + BMSCs in HCC development through regulating miR-140 and Wnt/β-catenin signal pathway.
Engineering Students as Co-creators in an Ethics of Technology Course
Authors: Bombaerts Gunter , Doulougeri Karolina , Tsui Shelly , Laes Erik , Spahn Andreas , Martin Diana Adela
Published: July 2021

Research on the effectiveness of case studies in teaching engineering ethics in higher education is underdeveloped. To add to our knowledge, we have systematically compared the outcomes of two case approaches to an undergraduate course on the ethics of technology: a detached approach using real-life cases and a challenge-based learning (CBL) approach with students and stakeholders acting as co-creators (CC). We first developed a practical typology of case-study approaches and subsequently tested an evaluation method to assess the students’ learning experiences (basic needs and motivation) and outcomes (competence development) and staff interpretations and operationalizations, seeking to answer three questions: (1) Do students in the CBL approach report higher basic needs, motivation and competence development compared to their peers in the detached approach? (2) What is the relationship between student-perceived co-creation and their basic needs, motivation and competence development? And (3) what are the implications of CBL/CC for engineering-ethics teaching and learning? Our mixed methods analysis favored CBL as it best supported teaching and research goals while satisfying the students’ basic needs and promoting intrinsic motivation and communication competences. Competence progress in other areas did not differ between approaches, and motivation in terms of identified regulation was lower for CBL, with staff perceiving a higher workload. We propose that our case typology model is useful and that as a method to engage students as co-creators, CBL certainly merits further development and evaluation, as does our effectiveness analysis for engineering ethics instruction in general and for case-study approaches in particular.
Archives and Transitional Justice in Chile: A Crucial Relationship
Authors: Ferrara Anita
Published: July 2021

The article, through the case study of Chile, explores the interconnections between archives, human rights and transitional justice. Chile represents a unique case globally for the early creation of thousands of records documenting the human rights violations committed under Pinochet’s 17-year dictatorship. In post-Pinochet Chile, the human rights archives have provided extremely important sources of evidence that have proven crucial in the development of transitional justice mechanisms. Truth commissions have, in turn, created their own archives, which have strongly contributed to later processes of reparation, justice and memory. The article aims to develop a better understanding of the multiple roles that archives have played as tools for achieving truth, justice and reparation over the long transitional period in Chile. The article argues that a combination of several factors and the intervention of different actors led to the archives having a significant impact in the development of subsequent transitional justice mechanisms.
3D Characterization of Acetabular Deficiency in Children with Developmental Dysplasia of the Hip
Authors: Badrinath Raghav , Jeffords Megan E. , Bomar James D. , Ahmed S. Imraan , Pennock Andrew T. , Upasani Vidyadhar V.
Published: July 2021

Background

The purpose of this study is to determine if a quantitative method can be used to identify differences in 3D morphology between normal and developmentally dysplastic hips and to identify specific areas of undercoverage in children with DDH compared to age- and sex-matched controls.

Methods

Subjects were included if they were typically developing children with no other underlying conditions affecting their musculoskeletal system and had an available pelvic CT scan (67 hips). Custom software was used to measure standard variables defining acetabular morphology (version, tilt, surface area). Acetabuli were divided into equal octants; coverage angles were measured for each octant of interest. Variables were compared with age- and sex-matched controls (128 hips) using analysis of variance or the Mann–Whitney test.

Results

Hips with DDH were more anteverted compared to normal hips (DDH: 22.6˚, Control: 16.4˚, p < 0.001). The surface area was similar between groups. 28% of hips had a global deficiency, 24% were anteriorly deficient, 19% were laterally deficient, 10% were anteverted (under covered anteriorly and over covered posteriorly), 3% were posteriorly deficient, and 15% of hips had borderline undercoverage. None of the hips in this cohort were found to be retroverted.

Conclusions

This is the first study to quantify the 3D acetabular deficiency in children with DDH compared to age- and sex-matched controls. We found wide variability in coverage patterns among dysplastic hips. It is imperative to define the specific acetabular deficiency for each individual patient prior to surgical correction.

Level of evidence

III – Case–control study.