bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscular weakness and muscle wasting in the critically ill
Authors: Schefold Joerg C. , Wollersheim Tobias , Grunow Julius J. , Luedi Markus M. , Z'Graggen Werner J. , Weber‐Carstens Steffen
Published: September 2020

Background

Muscular weakness and/or muscle wasting is recognized as a key medical problem in critically ill patients on intensive care units (ICUs) worldwide.

Methods and Results

Intensive care unit‐acquired weakness (ICUAW) results from various diseases leading to critical illness and is observed in about 40% [1080/2686 patients, 95% confidence interval (CI): 38–42%] of mixed (medical–surgical) ICU patients. Muscle strength at ICU discharge is directly associated with mortality 5 years after discharge [hazard ratio 0.946, 95% CI: 0.928–0.968 per point increase in Medical Research Council (MRC) scores, P = 0.001]. ICUAW serves as umbrella term for the subgroups ‘critical illness myopathy’, ‘critical illness polyneuropathy’, and ‘critical illness polyneuromyopathy’, the latter distinguished using electrophysiology and/or biopsy studies. Diagnosing, studying, and developing treatments for ICUAW among the critically ill seems challenging due to the acuity and severity of the underlying heterogeneous diseases. Ventilator‐induced diaphragmatic dysfunction occurs in up to 80% (n = 32/40) of ICUAW patients after mechanical ventilation and mostly results from distinct muscular pathologies, disuse, underlying critical illness, and/or effects imposed directly by mechanical ventilation. Swallowing disorders/dysphagia likely represent an additional (local) neuromuscular dysfunction/ICUAW sequelae and presents in 10.3% (n = 96/933) of mixed medical–surgical ICU survivors, with 60.4% (n = 58/96) of patients remaining dysphagia positive until hospital discharge. Key independent risk factors for dysphagia following mechanical ventilation are baseline neurological disease [odds ratio (OR) 4.45, 95% CI: 2.74–7.24, P < 0.01], emergency admission (OR 2.04, 95% CI: 1.15–3.59, P < 0.01), days on mechanical ventilation (OR 1.19, 95% CI: 1.06–1.34, P < 0.01), days on renal replacement therapy (OR 1.1, 95% CI: 1–1.23, P = 0.03), and disease severity (Acute Physiology and Chronic Health Evaluation II score within first 24 h; OR 1.03, 95% CI: 0.99–1.07, P < 0.01). Dysphagia positivity independently predicts 28‐day and 90‐day mortality (90‐day univariate hazard ratio: 3.74; 95% CI, 2.01–6.95; P < 0.001) and is associated with a 9.2% excess (all‐cause) mortality rate.

Conclusions

Neuromuscular weakness and muscle wasting is observed in many survivors of critical illness. ICUAW, ventilator‐induced diaphragmatic dysfunction, and dysphagia are associated with complicated and prolonged ICU stay, impaired weaning from mechanical ventilation, impeded rehabilitative measures, and a considerable impact on morbidity and mortality is noted. Future research strategies should further explore underlying pathomechanisms and lead to development of causal treatment strategies.
High‐power UHF Doherty amplifier output combiner network optimization by 3‐port sub‐circuit X‐parameters characterization
Authors: Cidronali Alessandro , Collodi Giovanni , Pagnini Lorenzo
Published: September 2020

This letter presents the optimization of the output combining network for a high‐power broadband Doherty power amplifier (DPA), based on the adoption of X‐parameters. The technique relies on the large‐signal vector network characterization of the prospective 3‐port DPA subcircuit. The characterization stage was carried out implementing the devices termination by the multisection artificial transmission line technique, thus allowing to terminate the devices with more accurate impedance value across the frequency band. This was validated by the development of the output combiner of a DPA prototype based on a pair of silicon laterally diffused MOSFETs (Si‐LDMOS). It was optimized in the band from 640 to 920 MHz, while the experimental characterization has been compared with a previous similar design. The DPA prototype exhibited a peak power of 54.4 dBm at centre frequency, with a peak drain efficiency (DE) up to 62% and 56% respectively at peak power and at 8‐dB input power back‐off. The data show a significant improvement with respect to the previous implementation of the same device technology and input network. This is due to the accuracy of the X‐parameter model based simulations, which is estimated to be 5.6 E‐3 in terms of normalized mean error.
A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD
Authors: Moore Mary P. , Cunningham Rory P. , Dashek Ryan J. , Mucinski Justine M. , Rector R. Scott
Published: September 2020

Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA‐approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high‐protein, plant‐based, low‐carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.
Wilms tumor
Authors: Pater Luke , Melchior Patrick , Rübe Christian , Cooper Benjamin T. , McAleer Mary Fran , Kalapurakal John A. , Paulino Arnold C.
Published: September 2020

The objectives for the treatment of Wilms tumor in both the Children's Oncology Group (COG) and the International Society of Paediatric Oncology (SIOP) have focused on improving cure rates and minimizing toxicity by limiting the use of radiation and doxorubicin. Although the timing of surgery is different in COG (upfront surgery) and SIOP (upfront chemotherapy with delayed surgery), both are effective strategies and have the same survival. Fewer patients are treated with radiotherapy in the SIOP trials but with higher doses. The prognostic significance of biological markers such as 1q gain and clinical outcomes with novel radiation techniques such as intensity modulated radiation therapy will be determined in upcoming clinical trials. A closer collaboration between COG and SIOP could help promote research and improve the clinical outcomes of children with Wilms tumor.
Using a home oxygen weaning protocol and pCO2 to evaluate outcomes for infants with bronchopulmonary dysplasia discharged on home oxygen
Authors: Dawson Sara K. , D'Andrea Lynn A. , Lau Ryan , Lagatta Joanne M.
Published: September 2020

Background

Predischarge capillary blood gas partial pressure of carbon dioxide (pCO2) has been associated with increased adverse events including readmission. This study aimed to determine if predischarge pCO2 or 36‐week pCO2 was associated with increased respiratory readmissions or other pulmonary healthcare utilization in the year after neonatal intensive care unit (NICU) discharge for infants with bronchopulmonary dysplasia (BPD) discharged with home oxygen, using a standardized outpatient oxygen weaning protocol.

Methods

This was a secondary cohort analysis of infants born <32 weeks gestational age with BPD, referred to our clinic for home oxygen therapy from either from our level IV NICU or local level III NICUs between 2015 and 2017. Infants with major nonrespiratory comorbidities were excluded. Subject information was obtained from electronic health records.

Results

Of 125 infants, 120 had complete 1‐year follow‐up. Twenty‐three percent of infants experienced a respiratory readmission after NICU discharge. There was no significant association between predischarge or 36‐week pCO2 and respiratory readmissions, emergency room visits, new or increased bronchodilators, or diuretics. Higher 36‐week pCO2 was associated with a later corrected age when oxygen was discontinued (<6 months; median, 54 mmHg; interquartile range [IQR], 51–61; 6–11 months; median, 62 mmHg; IQR, 57–65; ≥12 months, median, 66 mmHg; IQR, 58–73; p = .006).

Conclusions

Neither predischarge pCO2 nor 36‐week pCO2 was associated with 1‐year respiratory readmissions. However higher pCO2 at 36 weeks was associated with a longer duration of home oxygen. Neonatal illness measures like 36‐week pCO2 may be useful in communicating expectations for home oxygen therapy to families.
N‐butanol extract of Hedyotis diffusa protects transgenic Caenorhabditis elegans from Aβ‐induced toxicity
Authors: DanQing Li , YuJie Guo , ChengPeng Zhang , HongZhi Du , Yi Hong , BiSheng Huang , Yan Cao
Published: September 2020

Hedyotis diffusa Willd (Rubiaceae) is a widely used and resourceful traditional Chinese medicine that exerts protection against aging and age‐related diseases. However, the underlying mechanisms of the protective effects remain largely unclear. Alzheimer's disease (AD) is an age‐related neurodegenerative disease, of which β‐amyloid (Aβ)‐induced toxicity has been suggested as a main cause. Herein, we use the transgenic Caenorhabditis elegans CL4176, CL2006, and CL2355 strains, which express human Aβ1‐42 peptide, to investigate the effects and the possible mechanisms of n‐butanol extract of H.diffusa (HDB)‐mediated protection against Aβ toxicity in vivo. During the experiments, a method of quality control for HDB was established by HPLC. Additionally, we examined the effects of HBD on gene expression changes with qRT‐PCR, aggregation of Aβ plagues with thioflavin‐S staining, and protein detection with GFP labeling. HDB improved lifespan, locomotion, and stress resistance. Further study showed that HDB decreased paralysis, the accumulation of ROS, and AChE activity. Moreover, HDB suppressed neuronal Aβ‐expression‐induced defects in chemotaxis behavior and increased SOD activity. HDB also downregulated the Aβ mRNA level and decreased the number of Aβ deposits. Furthermore, HDB increased the expression levels of sod‐3, daf‐16, hsf‐1, and hsp‐16.2 gene and upregulated hsp‐16.2::GFP and gst‐4::GFP expression. Taken together, these results suggest that HDB may protect against Aβ‐induced toxicity in C. elegans via the insulin/insulin‐like growth factor‐1 (IGF‐1) signaling pathway.
Robust estimation for linear panel data models
Authors: Hamiye Beyaztas Beste , Bandyopadhyay Soutir
Published: September 2020

In different fields of applications including, but not limited to, behavioral, environmental, medical sciences, and econometrics, the use of panel data regression models has become increasingly popular as a general framework for making meaningful statistical inferences. However, when the ordinary least squares (OLS) method is used to estimate the model parameters, presence of outliers may significantly alter the adequacy of such models by producing biased and inefficient estimates. In this work, we propose a new, weighted likelihood based robust estimation procedure for linear panel data models with fixed and random effects. The finite sample performances of the proposed estimators have been illustrated through an extensive simulation study as well as with an application to blood pressure dataset. Our thorough study demonstrates that the proposed estimators show significantly better performances over the traditional methods in the presence of outliers and produce competitive results to the OLS based estimates when no outliers are present in the dataset.
Enriching the design of Alzheimer's disease clinical trials: Application of the polygenic hazard score and composite outcome measures
Authors: Banks Sarah J. , Qiu Yuqi , Fan Chun Chieh , Dale Anders M. , Zou Jingjing , Askew Brianna , Feldman Howard H. ,   For the Alzheimer's Disease Neuroimaging Initiative
Published: September 2020

Introduction

Selecting individuals at high risk of Alzheimer's disease (AD) dementia and using the most sensitive outcome measures are important aspects of trial design.

Methods

We divided participants from Alzheimer's Disease Neuroimaging Initiative at the 50th percentile of the predicted absolute risk of the polygenic hazard score (PHS). Outcome measures were the Alzheimer's Disease Assessment Schedule‐Cognitive Subscale (ADAS‐Cog), ADNI‐Mem, Clinical Dementia Rating‐Sum of Boxes (CDR SB), and Cognitive Function Composite 2 (CFC2). In addition to modeling, we use a power analysis compare numbers needed with each technique.

Results

Data from 188 cognitively normal and 319 mild cognitively impaired (MCI) participants were analyzed. Using the ADAS‐Cog to estimate sample sizes, without stratification over 24 months, would require 930 participants with MCI, while using the CFC2 and restricting participants to those in the upper 50th percentile would require only 284 participants.

Discussion

Combining stratification by PHS and selection of a sensitive combined outcome measure in a cohort of patients with MCI can allow trial design that is more efficient, potentially less burdensome on participants, and more cost effective.
A new way of calculating the effective potential for a light radion
Authors: Lizana J.M. , Olechowski M. , Pokorski S.
Published: September 2020

Abstract

We address again the old problem of calculating the radion effective potential in Randall-Sundrum scenarios, with the Goldberger-Wise stabilization mechanism. Various prescriptions have been used in the literature, most of them based on heuristic derivations and then applied in some approximations. We define rigorously a light radion 4D effective action by using the interpolating field method. For a given choice of the interpolating field, defined as a functional of 5D fields, the radion effective action is uniquely defined by the procedure of integrating out the other fields, with the constrained 5D equations of motion always satisfied with help of the Lagrange multipliers. Thus, for a given choice of the interpolating fields we obtain a precise prescription for calculating the effective potential. Different choices of the interpolating fields give different prescriptions but in most cases very similar effective potentials. We confirm the correctness of one prescription used so far on a more heuristic basis and also find several new, much more economical, ways of calculating the radion effective potential. Our general considerations are illustrated by several numerical examples. It is shown that in some cases the old methods, especially in models with strong back-reaction, give results which are off even by orders of magnitude. Thus, our results are important e.g. for estimation of critical temperature in phase transitions.
Cardiopulmonary Exercise Testing Versus Frailty, Measured by the Clinical Frailty Score, in Predicting Morbidity in Patients Undergoing Major Abdominal Cancer Surgery
Authors: O'Mahony M. , Mohammed K. , Kasivisvanathan R.
Published: September 2020

Background

The primary outcome of this study is to investigate the association between the cardiopulmonary exercise testing (CPET) variables: anaerobic threshold (AT), peak oxygen uptake (VO2 peak), peak work rate (WR), ventilatory equivalence of CO2 (VE/VCO2) at the anaerobic threshold (AT) with frailty, measured by the clinical frailty scale (CFS) in patients planned to undergo major abdominal cancer surgery. The secondary outcome is to compare the CPET variables (VO2 peak, peak WR, VE/VCO2 at AT) with frailty measured by the CFS in predicting postoperative surgical morbidity in patients following major abdominal cancer surgery.

Methods

This study was a single‐centre prospective cohort analysis of consecutive adult patients undergoing CPET and CFS scoring as part of their pre‐operative work‐up for major abdominal cancer surgery.

Results

A total of n = 317 patients underwent CPET and CFS assessment ahead of planned abdominal oncological surgery. Negative correlations were observed between the CPET variables: AT − 0.42 p < 0.01; VO2 peak − 0.53 p < 0.01; peak WR − 0.54 p < 0.01 with CFS scores and a positive correlation between CFS scores and VE/VCO2 0.29 p < 0.01. Only CFS remained statistically significant in a multivariate model OR 2.11 (1.42–3.15) 95% CI associated with Clavien–Dindo (CD) ≥ 1 defined morbidity including the significant univariate variables (VO2 peak, peak WR and CFS scores). No variables were associated with CD ≥ 3 morbidity.

Conclusions

In patients scheduled to have major abdominal cancer surgery there was a weak association between poor performance on CPET and increasing frailty measured by the CFS. The CFS score unlike CPET was associated with all post‐operative morbidity, but not major complications alone, in these patients. This suggests that CFS may be used as a less expensive alternative to CPET for predicting any postoperative morbidity in major abdominal cancer surgery.
Relations between structural characteristics, forest involvement, and forest knowledge among private forest owners in Sweden
Authors: Eriksson Louise , Fries Clas
Published: September 2020

An understanding of private forest owners is needed for appropriate forest governance and outreach to forest owners. This study examined different types of objective and subjective knowledge (i.e., actual knowledge and confidence, respectively), including general forest knowledge and knowledge of management for different objectives, among individual private forest owners in Sweden. In addition, the importance of structural variables (e.g., gender, size of forest holding) and forest involvement variables (e.g., certification, involvement in forest planning) for forest knowledge was analysed. The study was conducted by means of a postal questionnaire to a random sample of private forest owners in Sweden (n = 3000, response rate 43%). Structural variables, but particularly involvement variables, were found to be related to subjective and objective knowledge. Being a male owner, owning a larger forest holding, having bought the land, and having owned the forest a long time were associated with higher subjective knowledge, or confidence, in managing the forest. Although being a male owner, for example, was also associated with higher levels of objective knowledge, the correlation diminished when controlling for forest involvement. The study considers the role of learning environments for forest owners and highlights the need to elaborate on the conceptualization and measurement of forest knowledge to understand the links between structural characteristics, forest involvement, and forest knowledge among private forest owners.
Cyclic and multilevel causation in evolutionary processes
Authors: Warrell Jonathan , Gerstein Mark
Published: September 2020

Many models of evolution are implicitly causal processes. Features such as causal feedback between evolutionary variables and evolutionary processes acting at multiple levels, though, mean that conventional causal models miss important phenomena. We develop here a general theoretical framework for analyzing evolutionary processes drawing on recent approaches to causal modeling developed in the machine-learning literature, which have extended Pearls do-calculus to incorporate cyclic causal interactions and multilevel causation. We also develop information-theoretic notions necessary to analyze causal information dynamics in our framework, introducing a causal generalization of the Partial Information Decomposition framework. We show how our causal framework helps to clarify conceptual issues in the contexts of complex trait analysis and cancer genetics, including assigning variation in an observed trait to genetic, epigenetic and environmental sources in the presence of epigenetic and environmental feedback processes, and variation in fitness to mutation processes in cancer using a multilevel causal model respectively, as well as relating causally-induced to observed variation in these variables via information theoretic bounds. In the process, we introduce a general class of multilevel causal evolutionary processes which connect evolutionary processes at multiple levels via coarse-graining relationships. Further, we show how a range of fitness models can be formulated in our framework, as well as a causal analog of Prices equation (generalizing the probabilistic Rice equation), clarifying the relationships between realized/probabilistic fitness and direct/indirect selection. Finally, we consider the potential relevance of our framework to foundational issues in biology and evolution, including supervenience, multilevel selection and individuality. Particularly, we argue that our class of multilevel causal evolutionary processes, in conjunction with a minimum description length principle, provides a conceptual framework in which identification of multiple levels of selection may be reduced to a model selection problem.
Female Audit Partners and Extended Audit Reporting: UK Evidence
Authors: Abdelfattah Tarek , Elmahgoub Mohamed , Elamer Ahmed A.
Published: September 2020

This study investigates whether audit partner gender is associated with the extent of auditor disclosure and the communication style regarding risks of material misstatements that are classified as key audit matters (KAMs). Using a sample of UK firms during the 2013–2017 period, our results suggest that female audit partners are more likely than male audit partners to disclose more KAMs with more details after controlling for both client and audit firm attributes. Furthermore, female audit partners are found to use a less optimistic tone and provide less readable audit reports, compared to their male counterparts, suggesting that behavioural variances between female and male audit partners may have significant implications on their writing style. Therefore, this study offers new insights on the role of audit partner gender in extended audit reporting. Our findings have important implications for audit firms, investors, policymakers and governments in relation to the development, implementation and enforcement of gender diversity.
Testing machine learning based systems: a systematic mapping
Authors: Riccio Vincenzo , Jahangirova Gunel , Stocco Andrea , Humbatova Nargiz , Weiss Michael , Tonella Paolo
Published: September 2020

Context:

A Machine Learning based System (MLS) is a software system including one or more components that learn how to perform a task from a given data set. The increasing adoption of MLSs in safety critical domains such as autonomous driving, healthcare, and finance has fostered much attention towards the quality assurance of such systems. Despite the advances in software testing, MLSs bring novel and unprecedented challenges, since their behaviour is defined jointly by the code that implements them and the data used for training them.

Objective:

To identify the existing solutions for functional testing of MLSs, and classify them from three different perspectives: (1) the context of the problem they address, (2) their features, and (3) their empirical evaluation. To report demographic information about the ongoing research. To identify open challenges for future research.

Method:

We conducted a systematic mapping study about testing techniques for MLSs driven by 33 research questions. We followed existing guidelines when defining our research protocol so as to increase the repeatability and reliability of our results.

Results:

We identified 70 relevant primary studies, mostly published in the last years. We identified 11 problems addressed in the literature. We investigated multiple aspects of the testing approaches, such as the used/proposed adequacy criteria, the algorithms for test input generation, and the test oracles.

Conclusions:

The most active research areas in MLS testing address automated scenario/input generation and test oracle creation. MLS testing is a rapidly growing and developing research area, with many open challenges, such as the generation of realistic inputs and the definition of reliable evaluation metrics and benchmarks.
Analysing the socio-technical transition to conservation agriculture in Uganda through the lens of the multi-level perspective
Authors: Kaweesa Sara Helen , Bilali Hamid El , Loiskandl Willibald
Published: September 2020

Conservation agriculture (CA) is based on three principles, namely minimum tillage, crop rotations and maintaining a soil cover. The research used the multi-Level perspective on socio-technical transitions to analyse the dynamics of CA in Uganda. The analysis of the CA niche is structured along the socio-technical regimes and explores the impact of the transition. Data were gathered from Alebtong, Dokolo and Lira districts in mid-Northern Uganda. The results indicate a steady transition towards CA that can be supported to eventually scale up. The legitimisation process of CA transition involved wider implementation by farmers on their fields, validation through adoption by the wider communities and at the national level. The process seeks policy and institutional promotion, more scientific publications of local research findings, validation by legal standards and judicial reasoning, raising civic awareness, stakeholder dialogue and mobilisation of political will to advance the purposes of CA in contrast to conventional agriculture. CA caused changes in practices, perceptions and motivation among the niche actors with respect to agricultural sustainability. However, scaling up could further be enhanced when market policies, credit and financial environment are reconciled.
Diabetes-related cardiovascular and economic burden in patients hospitalized for heart failure in the US: a recent temporal trend analysis from the National Inpatient Sample
Authors: Mekhaimar Menatalla , Dargham Soha , El-Shazly Mohamed , Al Suwaidi Jassim , Jneid Hani , Abi Khalil Charbel
Published: September 2020

We aimed to study the cardiovascular and economic burden of diabetes mellitus (DM) in patients hospitalized for heart failure (HF) in the US and to assess the recent temporal trend. Data from the National Inpatient Sample were analyzed between 2005 and 2014. The prevalence of DM increased from 40.4 to 46.5% in patients hospitalized for HF. In patients with HF and DM, mean (SD) age slightly decreased from 71 (13) to 70 (13) years, in which 47.5% were males in 2005 as compared with 52% in 2014 (p trend < 0.001 for both). Surprisingly, the presence of DM was associated with lower in-hospital mortality risk, even after adjustment for confounders (adjusted OR = 0.844 (95% CI [0.828–0.860]). Crude mortality gradually decreased from 2.7% in 2005 to 2.4% in 2014 but was still lower than that of non-diabetes patients’ mortality on a yearly comparison basis. Hospitalization for HF also decreased from 211 to 188/100,000 hospitalizations. However, median (IQR) LoS slightly increased from 4 (2–6) to 4 (3–7) days, so did total charges/stay that jumped from 15,704 to 26,858 USD (adjusted for inflation, p trend < 0.001 for both). In total, the prevalence of DM is gradually increasing in HF. However, the temporal trend shows that hospitalization and in-hospital mortality are on a descending slope at a cost of an increasing yearly expenditure and length of stay, even to a larger extent than in patient without DM.
Floquet Multipliers of a Periodic Solution Under State-Dependent Delay
Authors: Mur Voigt Therese , Walther Hans-Otto
Published: September 2020

We consider a periodic function $$p:{\mathbb {R}}\rightarrow {\mathbb {R}}$$

p
:
R
→
R

of minimal period 4 which satisfies a family of delay differential equations $$\begin{aligned} x'(t)=g(x(t-d_{\Delta }(x_t))),\quad \Delta \in {\mathbb {R}}, \end{aligned}$$

x
′

(
t
)

=
g

(
x

(
t
-

d
Δ

(

x
t

)

)

)

,

Δ
∈
R
,

with a continuously differentiable function $$g:{\mathbb {R}}\rightarrow {\mathbb {R}}$$

g
:
R
→
R

and delay functionals $$\begin{aligned} d_{\Delta }:C([-2,0],{\mathbb {R}})\rightarrow (0,2). \end{aligned}$$

d
Δ

:
C

(

[
-
2
,
0
]

,
R
)

→

(
0
,
2
)

.

The solution segment $$x_t$$

x
t

in Eq. (0.1) is given by $$x_t(s)=x(t+s)$$

x
t

(
s
)

=
x

(
t
+
s
)

. For every $$\Delta \in {\mathbb {R}}$$

Δ
∈
R

the solutions of Eq. (0.1) defines a semiflow of continuously differentiable solution operators $$S_{\Delta ,t}:x_0\mapsto x_t$$

S

Δ
,
t

:

x
0

↦

x
t

, $$t\ge 0$$

t
≥
0

, on a continuously differentiable submanifold $$X_{\Delta }$$

X
Δ

of the space $$C^1([-2,0],{\mathbb {R}})$$

C
1

(

[
-
2
,
0
]

,
R
)

, with codim $$X_{\Delta }=1$$

X
Δ

=
1

. At $$\Delta =0$$

Δ
=
0

the delay is constant, $$d_0(\phi )=1$$

d
0

(
ϕ
)

=
1

everywhere, and the orbit $${{\mathcal {O}}}=\{p_t:0\le t<4\}\subset X_0$$

O
=

{

p
t

:
0
≤
t
<
4
}

⊂

X
0

of the periodic solution is extremely stable in the sense that the spectrum of the monodromy operator $$M_0=DS_{0,4}(p_0)$$

M
0

=
D

S

0
,
4

(

p
0

)

is $$\sigma _0=\{0,1\}$$

σ
0

=

{
0
,
1
}

, with the eigenvalue 1 being simple. For $$|\Delta |\nearrow \infty $$

|
Δ
|
↗
∞

there is an increasing contribution of variable, state-dependent delay to the time lag $$d_{\Delta }(x_t)=1+\cdots $$

d
Δ

(

x
t

)

=
1
+
⋯

in Eq. (0.1). We study how the spectrum $$\sigma _{\Delta }$$

σ
Δ

of $$M_{\Delta }=DS_{\Delta ,4}(p_0)$$

M
Δ

=
D

S

Δ
,
4

(

p
0

)

changes if $$|\Delta |$$

|
Δ
|

grows from 0 to $$\infty $$
∞
. A main result is that at $$\Delta =0$$

Δ
=
0

an eigenvalue $$\Lambda (\Delta )<0$$

Λ
(
Δ
)
<
0

of $$M_{\Delta }$$

M
Δ

bifurcates from $$0\in \sigma _0$$

0
∈

σ
0

and decreases to $$-\infty $$

-
∞

as $$|\Delta |\nearrow \infty $$

|
Δ
|
↗
∞

. Moreover we verify the spectral hypotheses for a period doubling bifurcation from the periodic orbit $${{\mathcal {O}}}$$
O
at the critical parameter $$\Delta _{*}$$

Δ

∗

where $$\Lambda (\Delta _{*})=-1$$

Λ
(

Δ

∗

)
=
-
1

.
Brief Mating Behavior at Dawn and Dusk and Long Nocturnal Matings in the Butterfly Melanitis leda
Authors: Molleman Freerk , Halali Sridhar , Kodandaramaiah Ullasa
Published: September 2020

Information on the mating system of an insect species is necessary to gain insight into sexual selection and population structure. Male territoriality of the common evening brown butterflyMelanitis ledahas been studied in the wild, but other aspects of its mating system remain largely unknown. For a population ofM. ledain South India, we observed male-male and male-female interactions in captivity, measured mating duration and spermatophore mass, and also determined the degree of polyandry in the wild. We found that mating behavior takes place for short periods of time around dawn and dusk. Our observations corroborate that males compete in aerial combats (twirling) and interfere with mating pairs. In the morning, they may use shivering to warm up. Females can twirl with males and refuse mating by pointing their abdomens upwards or by flying away. Males court females by fluttering their wings while perched behind females, and then initiate copulation by curling their abdomens ca. 180 degrees sideways to make genital contact. While in the morning, matings lasted on average one hour and twenty-three minutes and never exceeded three hours, in the evening, matings could be of similar duration, but 42% of butterflies only separated when dawn was approaching. However, such long nocturnal matings did not result in heavier spermatophores. The first spermatophore of a male tended to be larger than subsequent spermatophores. Together with previous studies on this species, our findings suggest that males compete mainly through territorial defense (as reported before), courtship performance, and interference, and to a lesser extent by providing spermatophores, while females exert some control over the mating system by the timing of their receptivity and mate choice.
Complementing Agents with Cognitive Services: A Case Study in Healthcare
Authors: Montagna Sara , Mariani Stefano , Gamberini Emiliano , Ricci Alessandro , Zambonelli Franco
Published: September 2020

Personal Agents (PAs) have longly been explored as assistants to support users in their daily activities. Surprisingly, few works refer to the adoption of PAs in the healthcare domain, where they can assist physicians’ activities reducing medical errors. Although literature proposes different approaches for modelling and engineering PAs, none of them discusses how they can be integrated with cognitive services in order to empower their reasoning capabilities. In this paper we present an integration model, specifically devised for healthcare applications, that enhances Belief-Desire-Intention agents reasoning with advanced cognitive capabilities. As a case study, we adopt this integrated model in the critical care path of trauma resuscitation, stepping forward to the vision of Smart Hospitals.
Population pharmacokinetics and pharmacodynamics of a novel vascular adhesion protein-1 inhibitor using a multiple-target mediated drug disposition model
Authors: Snelder Nelleke , Hoefman Sven , Garcia-Hernandez Alberto , Onkels Hartmut , Larsson Tobias E. , Bergmann Kirsten R.
Published: September 2020

ASP8232 is a novel inhibitor of vascular adhesion protein-1 that was under evaluation for reducing residual albuminuria in patients with diabetic kidney disease. To characterize the pharmacokinetics (PK) of ASP8232 and its effect on vascular adhesion protein 1 (VAP-1) plasma activity and VAP-1 concentrations (pharmacodynamics, PD) in an integrated and quantitative manner, a target mediated drug disposition model was developed based on pooled data from four completed clinical trials with ASP8232 in healthy volunteers, and in patients with diabetic kidney disease and diabetic macular edema, respectively. In this model, the binding of ASP8232 to its soluble and membrane-bound target in the central and peripheral compartments were included. The model was able to adequately describe the non-linear PK and PD of ASP8232. The observed difference in PK between healthy volunteers and renally impaired patients could be explained by an effect of baseline estimated glomerular filtration rate on ASP8232 clearance and relative bioavailability. The relationship between ASP8232 concentration and VAP-1 inhibition was successfully established and can be applied to simulate drug exposure and degree of VAP-1 inhibition for any given dose of ASP8232 across the spectrum of renal function.
Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN)
Authors: Ford Janet , Tassorelli Cristina , Leroux Elizabeth , Wang Shufang , Ayer David , Nichols Russell , Detke Holland
Published: September 2020

Purpose

To evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine.

Methods

Patients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQv2.1) measured the impact of migraine on patient functioning. The Migraine Disability Assessment (MIDAS) quantified headache-related disability. Changes from baseline were analyzed with mixed model repeated measures or analysis of covariance.

Results

Total MSQ score at baseline was 44.88 ± 18.02 (mean ± SD), indicating significant functional impairment. At Month 3, least squares (LS) mean change ± SE in total MSQ for galcanezumab-treated patients were 20.51 ± 1.49 (120 mg) and 20.49 ± 1.49 (240 mg), both statistically significantly greater vs placebo-treated patients (14.55 ± 1.21; both P < 0.001). Total MIDAS score at baseline was 67.24 ± 57.31 (mean ± SD). At Month 3, LS mean change ± SE from baseline in total MIDAS for galcanezumab-treated patients was statistically significantly greater than placebo for 120 mg group (placebo: − 11.53 ± 3.38 vs 120 mg: − 20.27 ± 4.07; P < 0.05) but not for 240 mg group (− 17.02 ± 4.05). At Month 12, within-group mean changes from baseline for total MSQ (28.56 ± 1.19 previous placebo; 29.53 ± 1.51 previous 120 mg; 25.83 ± 1.49 previous 240 mg) and MIDAS scores (− 28.47 ± 2.95 previous placebo; − 31.47 ± 3.69 previous 120 mg; − 31.13 ± 3.62 previous 240 mg) were statistically significant (P < 0.001) for the open-label treatment population regardless of previous double-blind treatment assignment.

Conclusions

Galcanezumab-treated patients with chronic migraine reported statistically significant improvements in functioning and disability, representing a clinically significant change.

Trial registration

ClinicalTrials.gov registry: NCT02614261. Registered 25 November 2015.
Creating Organisational Strength from Operationalising Restrictions: Welfare Non-profit Organisations in the Russian Federation
Authors: Crotty Jo , Ljubownikow Sergej
Published: September 2020

The work of non-profit organisations (NPOs) in non-democratic country contexts tends to be judged on their contribution to the democratisation process rather than the activities they undertake.
This neglects the potential impact NPOs have on societies within such contexts. In this study, we highlight that NPOs can influence public policy deployment in the Russian Federation even if they cannot affect public policy itself. By operationalising the very restrictions placed upon them, NPOs use their relationships with the state to effect change within their immediate environment and scope of their operational remit, even if they cannot hold authorities to account or influence policy development. The key to this is strong organising capabilities and engagement with the Russian public. We reflect on the implications of our findings to the understanding of civil society development and NPOs in Russia and in other similar non-democratic contexts.
Correction to: At the US Epicenter of the COVID-19 Pandemic, an Orthopedic Residency Program Reorganizes
Authors: Morse Kyle W. , Wessel Lauren E. , Premkumar Ajay , James Evan W. , Anatone Alex J. , Barth Kathryn , Bovonratwet Patawut , Jordan Yusef , Retzky Julia , Suhardi Vincentius , Thacher Ryan , Uppstrom Tyler , Yang Brian , Bido Jennifer , Carey Edward , Defrancesco Christopher , Elbuluk Ameer , Lebrun Drake , Ondeck Nathaniel , Pompeu Yuri , Schimizzi Gregory , Shafi Karim , Apostolakos John M. , Barber Lauren A. , Brusalis Christopher M. , Driscoll Daniel A. , Ellsworth Bridget , Langhans Mark , Shen Tony , Wright-Chisem Joshua , Conti Matthew , Eliasberg Claire , Goeb Yannick , Henry Jensen , Lin Kenneth M. , Lovecchio Francis , Samuel Andre , Dvorzhinskiy Aleksey , Goodbody Christine , Gruskay Jordan , Heaps Braiden , Hurwit Daniel , Kahlenberg Cynthia , Rauck Ryan , Steinhaus Michael , Bostrom Mathias , Cross Michael , Fabricant Peter D. , Felix Karla , Green Daniel , Kim Han Jo , Leali Alejandro , Memnon Carle-Marie , O'Brasky Martha , Ranawat Anil , Robbins Laura , Nwachukwu Benedict U. , Fufa Duretti T.
Published: September 2020

The published article contained four sentences with incorrect reference citations. Here, those sentences and the reference list are corrected.
Public Interest in Knee Replacement Fell during the Onset of the COVID-19 Pandemic: A Google Trends Analysis
Authors: Landy David C. , Chalmers Brian P. , Utset-Ward Thomas J. , Ast Michael P.
Published: September 2020

Background

The COVID-19 pandemic significantly altered medical practice and public behavior in the USA. In spring of 2020, elective surgery including most joint replacement was suspended and much of the public asked to stay at home. As elective surgery resumes, it is unknown how the public will respond.

Questions/Purposes

We sought to describe public interest in knee replacement during the onset of the COVID-19 pandemic.

Methods

Google Trends was used to obtain the daily number of searches for “knee replacement,” “coronavirus,” and “knee pain” from December 19, 2019, to May 14, 2020. The number is on a term-specific scale weighted to the highest number of daily searches for that term. Seven-day weighted averages were used to smooth the data.

Results

The number of daily searches for “knee replacement” was stable until around March 8, 2020, after which it decreased through late March, plateauing at less than half the number of searches. At the same time, searches for “coronavirus” spiked. By early May, searches for “knee replacement” had not meaningfully increased, though at the end of the search period the slope turned positive and coronavirus searches decreased. Searches for “knee pain” initially followed a similar pattern to “knee replacement,” though the decline was not as steep, and by late April searches for “knee pain” had meaningfully increased.

Conclusion

Public interest in knee replacement, assessed through internet search queries, decreased during the onset of the COVID-19 pandemic. While interest in pain has returned, the continued decreased level of interest in surgery may represent a fear of surgery among the general public in the setting of COVID-19. Surgeons may wish to focus outreach and education efforts on the safety and efficacy of knee replacement.
Study of Structure and Properties of Fe-Based Amorphous Ribbons after Pulsed Laser Interference Heating
Authors: Czyż Olaf , Kusiński Jan , Radziszewska Agnieszka , Liao Zhongquan , Zschech Ehrenfried , Kąc Małgorzata , Ostrowski Roman
Published: September 2020

The paper is devoted to the study of microstructural and magnetic properties of the Fe-based amorphous ribbons after interference pulsed laser heating. The ternary amorphous alloy FeSiB, as well as the multi-component alloys FeCuSiB and FeCuNbSiB, was subjected to laser pulses to induce crystallization in many microislands simultaneously. Structure and properties changes occurred in laser-heated dots. Detailed TEM analysis from a single dot shows the presence of FeSi(α) nanocrystals in the amorphous matrix. The FeSiB alloy is characterized after conventional crystallization by a dendritic structure; however, the alloys with copper as well copper and niobium additions are characterized by the formation of equiaxed crystals in the amorphous matrix. Amorphous alloys before and after the laser heating are soft magnetic; however, conventional crystallization leads to a deterioration of the soft magnetic properties of the material.
Acceptability of online exercise-based interventions after breast cancer surgery: systematic review and narrative synthesis
Authors: Sotirova Mariya B. , McCaughan Eilís M. , Ramsey Lucia , Flannagan Carrie , Kerr Daniel P. , O’Connor Sean R. , Blackburn Nicole E. , Wilson Iseult M.
Published: September 2020

Purpose

eHealth and mHealth approaches are increasingly used to support cancer survivors. This review aimed to examine adherence, acceptability and satisfaction with Internet-based self-management programmes for post-surgical cancer rehabilitation and to identify common components of such interventions.

Methods

Nine electronic databases were searched from inception up to February 15, 2020, for relevant quantitative and qualitative studies evaluating Internet-based cancer rehabilitation interventions. Studies were required to include an exercise or physical activity–based self-management intervention and a measure of adherence, acceptability or user satisfaction with the programme. Two independent reviewers performed all data extraction and quality assessment procedures. Data were synthesized using a narrative approach.

Results

Six hundred ninety-six potential papers were identified and screened. Eleven met the inclusion criteria. Interventions had wide variations in levels of adherence, but the majority were reported as being acceptable to the users. Increased acceptability and user satisfaction were associated with interventions which were seen as time and cost-efficient, requiring acquisition of minimal or no new skills, which used coherent language, or which provided tailored information. The majority contained behaviour change components such as goal setting.

Conclusions

Despite high levels of heterogeneity between studies, Internet-based approaches may be an acceptable method for the delivery of self-management interventions in post-surgical cancer rehabilitation.

Implications for Cancer Survivors

There is a need for further studies exploring factors associated with increased user engagement and usage of digital interventions in cancer rehabilitation settings. These findings should be used to help develop interventions prior to testing their effectiveness in adequately powered randomized controlled trials.
Lower Levels of Blood Zinc Associated with Intradialytic Hypertension in Maintenance Hemodialysis Patients
Authors: Liu Yun , Zheng Yuanyuan , Wang Liangtao , Zhong Xiaoshi , Qin Danping , Chen Wenxuan , Tan Rongshao , Liu Yan
Published: September 2020

Intradialytic hypertension (iHTN) has been related with an increased risk of mortality, with imbalances in trace elements being frequent in maintenance hemodialysis (MHD) patients. The aim of this study was to analyze the relationships between the levels of blood trace elements and iHTN in MHD patients. A total of 144 MHD patients were enrolled in September, 2019 (66 females; 5616 hemodialysis treatments), with a mean age of 64.33 ± 13.39 years and median vintage of 33.50 (16.25–57.50) months. Patients exhibited an average peridialytic systolic blood pressure (SBP) change of − 4.18 ± 20.22 mm Hg in the next 3 months. Thirty-four (23.6%) patients had persistent iHTN (piHTN). These patients were characterized by older age, higher rate of hypozincemia, and modified Charlson comorbidity score, whereas lower blood zinc and hemoglobin, at the time of their recruitment. No significant difference in the levels of other blood trace elements was observed between groups. A general linear mixed (GLM) model showed that with every mg/L point lower mean blood zinc at baseline, the peridialytic SBP change was increased by 4.524 mm Hg (P< 0.001). Binary logistic model in modulate of the GLM model revealed that the lower level of blood zinc was associated with piHTN (OR = 0.433, 95 % CI 0.295 to 0.637,P< 0.001). Multivariate analysis confirmed both above results. Our study indicated that lower blood zinc was independently associated with piHTN in patients undergoing MHD, but prospective studies with larger population are still needed.
Distribution of nitrogen and oxygen compounds in shale oil distillates and their catalytic cracking performance
Authors: Chen Xiao-Bo , Zhang Xin-Yang , Qin Ru-Meng , Shan Sheng-Jie , Xia Pan-Deng , Li Nan , Pu Jun , Liu Ji-Xia , Liu Yi-Bin , Yang Chao-He
Published: September 2020

The positive- and negative-ion electrospray ionization (ESI) coupled with Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) was employed to identify the chemical composition of heteroatomic compounds in four distillates of Fushun shale oil, and their catalytic cracking performance was investigated. There are nine classes of basic nitrogen compounds (BNCs) and eleven classes of non-basic heteroatomic compounds (NBHCs) in the different distillates. The dominant BNCs are mainly basic N1 class species. The dominant NBHCs are mainly acidic O2 and O1 class species in the 300–350 °C, 350–400 °C, and 400–450 °C distillates, while the neutral N1, N1O1 and N2 compounds become relatively abundant in the > 450 °C fraction. The basic N1 compounds and acidic O1 and O2 compounds are separated into different distillates by the degree of alkylation (different carbon number) but not by aromaticity (different double-bond equivalent values). The basic N1O1 and N2 class species and neutral N1 and N2 class species are separated into different distillates by the degrees of both alkylation and aromaticity. After the catalytic cracking of Fushun shale oil, the classes of BNCs in the liquid products remain unchanged, while the classes and relative abundances of NBHCs vary significantly.