bluuebunny/crossref_metadata_2025 huggingface dataset:
The importance of socioeconomic conditions in mitigating climate change impacts and achieving Sustainable Development Goals
Authors: Liu Jing-Yu , Fujimori Shinichiro , Takahashi Kiyoshi , Hasegawa Tomoko , Wu Wenchao , Geng Yong , Takakura Jun’ya , Masui Toshihiko
Published: November 2020

Actions tackling with climate change can cause co-benefits and trade-offs with Sustainable Development Goals (SDGs) concerned with air pollution, water scarcity, food security, land use, and sustainable energy. Such interactions can be greatly influenced by socioeconomic conditions. The impacts of socioeconomic conditions on multiple SDGs have not been evaluated separately from climate policies. This paper employs a Representative Concentration Pathways–Shared Socio-economic Pathways (RCP-SSP) framework and the Asia-Pacific Integrated Model/computable general equilibrium (AIM/CGE) integrated assessment model to identify the global multi-sectoral consequences of socioeconomic conditions through 2050 under future SSP scenarios. Results show that changes of socioeconomic conditions consistent with the SSP1 pathway could always improve SDG indicators, with or without climate policies. In many respects, socioeconomic conditions are more important than climate policies in achieving SDGs, particularly SDGs concerned with food security and energy affordability, as well as in simultaneously achieving multiple SDGs. We conclude that the advantages of a joint effort to implement climate policies and promulgate socioeconomic changes should be recognized by policy makers.
Study of some rheological properties of niosomal dispersions of various concentrations based on PEG-12 dimethicone
Authors: Vecher O V , Diskaeva E I , Bazikov I A , Elbekyan K S , Diskaeva E N
Published: November 2020

In recent decades, the creation of new pharmaceutical targeted drug delivery has become widespread. In this regard, various carriers of medicinal substances have been developed. It is worthy to note that niosomes are more prospective in comparison with other carrier, because they are not susceptible to oxidation and they have delayed clearance, thus providing high therapeutic performance. This study aims to investigate some rheological properties of niosomal dispersion and the analysed dependence of viscosity coefficient on volume concentration. The results demonstrated that for low concentrations of niosomal dispersions, the dynamic viscosity coefficient can be estimated using the Einstein’s equation with the introduction of a correction factor, the value of which at an average diameter of 90–100 nm and a zeta potential of 49.5–54.5 mV is 0.04–0.05. It is wished that our work would be helpful to fully understand the structure of niosome aggregates, which are considered to play an important role in viscosity and are affected by both intermolecular and electrostatic forces. With increasing particle concentration and decreasing average distance between aggregates, the particles at the surface of different aggregates attract each other and a less compact aggregation structure is formed. The measured relationships between size, ζ-potential, and the relative viscosities of dispersions show that the relative viscosities decrease with decreasing absolute value of ζ-potential, which further reveals the effect of electrical repulsion forces on the structure of aggregates.
String^{𝑐} structures and modular invariants
Authors: Huang Ruizhi , Han Fei , Duan Haibao
Published: November 2020

In this paper, we study some algebraic topology aspects of String

c

^c

structures, more precisely, from the perspective of Whitehead tower and the perspective of the loop group of

S
p
i

n
c

(
n
)

Spin^c(n)

. We also extend the generalized Witten genera constructed for the first time by Chen et al. [J. Differential Geom. 88 (2011), pp. 1–40] to correspond to String

c

^c

structures of various levels and give vanishing results for them.
Approximating rational points on toric varieties
Authors: McKinnon David , Satriano Matthew
Published: November 2020

Given a smooth projective variety

X
X

over a number field

k
k

and

P
∈
X
(
k
)

P\in X(k)

, the first author conjectured that in a precise sense, any sequence that approximates

P
P

sufficiently well must lie on a rational curve. We prove this conjecture for smooth split toric surfaces conditional on Vojta’s conjecture. More generally, we show that if

X
X

is a

Q

\mathbb {Q}

-factorial terminal split toric variety of arbitrary dimension, then

P
P

is better approximated by points on a rational curve than by any Zariski dense sequence.
Higgs bundles over non-compact Gauduchon manifolds
Authors: Zhang Chuanjing , Zhang Pan , Zhang Xi
Published: November 2020

In this paper, we prove a generalized Donaldson-Uhlenbeck-Yau theorem on Higgs bundles over a class of non-compact Gauduchon manifolds.
Weak Siegel-Weil formula for 𝕄₂(ℚ) and arithmetic on quaternions
Authors: Du Tuoping
Published: November 2020

We prove a weak version of the Siegel-Weil formula on

SL
2

\operatorname {SL}_2

for the dual pair

(

SL
2

,

O

2
,
2

)

(\operatorname {SL}_2, O_{2, 2})

, where

O

2
,
2

O_{2, 2}

is the split orthogonal group. By this formula and the Siegel-Weil formula, we give explicit formulas for Hecke correspondence’s degree and average representation numbers over genus associated to Eichler orders. At last, we give explicit formulas for representations of a number as sums of three squares and four squares by local Whittaker functions, and it turns out that these functions are exactly the local factors of Hardy’s singular series.
Regularity of weak solutions to higher order elliptic systems in critical dimensions
Authors: Guo Chang-Yu , Xiang Chang-Lin
Published: November 2020

In this paper, we develop an elementary and unified treatment, in the spirit of Rivière and Struwe (Comm. Pure. Appl. Math. 2008), to explore regularity of weak solutions of higher order geometric elliptic systems in critical dimensions without using conservation law. As a result, we obtain an interior Hölder continuity for solutions of the higher order elliptic system of de Longueville and Gastel in critical dimensions
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="normal upper Delta Superscript k Baseline u equals sigma-summation Underscript i equals 0 Overscript k minus 1 Endscripts normal upper Delta Superscript i Baseline mathematical left-angle upper V Subscript i Baseline comma d u mathematical right-angle plus sigma-summation Underscript i equals 0 Overscript k minus 2 Endscripts normal upper Delta Superscript i Baseline delta left-parenthesis w Subscript i Baseline d u right-parenthesis in upper B Superscript 2 k Baseline comma">

Δ

k

u
=

∑

i
=
0

k
−
1

Δ

i

⟨

V

i

,
d
u
⟩

+

∑

i
=
0

k
−
2

Δ

i

δ

(

w

i

d
u
)

in 

B

2
k

,

\begin{equation*} \Delta ^{k}u=\sum _{i=0}^{k-1}\Delta ^{i}\left \langle V_{i},du\right \rangle +\sum _{i=0}^{k-2}\Delta ^{i}\delta \left (w_{i}du\right ) \quad \text {in } B^{2k}, \end{equation*}

under critical regularity assumptions on the coefficient functions. This verifies an expectation of Rivière, and provides an affirmative answer to an open question of Struwe in dimension four when

k
=
2

k=2

. The Hölder continuity is also an improvement of the continuity result of Lamm and Rivière and de Longueville and Gastel.
On the smallest base in which a number has a unique expansion
Authors: Allaart Pieter , Kong Derong
Published: November 2020

Given a real number

x
>
0

x>0

, we determine

q
s

(
x
)
≔
inf
⁡

U

(
x
)

q_s(x)≔\operatorname {inf}{\mathscr {U}}(x)

, where

U

(
x
)

{\mathscr {U}}(x)

is the set of all bases

q
∈
(
1
,
2
]

q\in (1,2]

for which

x
x

has a unique expansion of

0
0

’s and

1
1

’s. We give an explicit description of

q
s

(
x
)

q_s(x)

for several regions of

x
x

-values. For others, we present an efficient algorithm to determine

q
s

(
x
)

q_s(x)

and the lexicographically smallest unique expansion of

x
x

. We show that the infimum is attained for almost all

x
x

, but there is also a set of points of positive Hausdorff dimension for which the infimum is proper. In addition, we show that the function

q
s

q_s

is right-continuous with left-hand limits and no downward jumps, and characterize the points of discontinuity of

q
s

q_s

.

A large part of the paper is devoted to the level sets

L
(
q
)
≔
{
x
>
0
:

q
s

(
x
)
=
q
}

L(q)≔\{x>0:q_s(x)=q\}

. We show that

L
(
q
)

L(q)

is finite for almost every

q
q

, but there are also infinitely many infinite level sets. In particular, for the Komornik-Loreti constant

q

K
L

=
min
⁡

U

(
1
)
≈
1.787

q_{KL}=\operatorname {min}{\mathscr {U}}(1)\approx 1.787

we prove that

L
(

q

K
L

)

L(q_{KL})

has both infinitely many left- and infinitely many right accumulation points.
Disruption of the Diurnal Cortisol Hormone Pattern by Pesticide Use in a Longitudinal Study of Farmers in Thailand
Authors: Kongtip Pornpimol , Nankongnab Noppanun , Kallayanatham Nichcha , Pengpumkiat Sumate , Gore Rebecca , Pundee Ritthirong , Konthonbut Pajaree , Woskie Susan R
Published: November 2020

Abstracts

Alteration of the hypothalamic–pituitary–adrenal (HPA) axis hormones has been associated with a range of chronic metabolic and cardiovascular health conditions. This study evaluated whether type of farming (organic versus conventional) or the number of self-reported days of spraying pesticides in the past 8 months was associated with diurnal cortisol levels. Salivary cortisol levels were measured four times a day (waking, 30 min after waking, 6 h after waking and bedtime) longitudinally, 8 months apart during three rounds of data collection. Pesticide using (conventional) and organic farmers were recruited to participate. Pesticide use in the previous 8 months was determined as the number of spray days for each type of pesticide used (herbicide, insecticide, fungicide) from self-reported questionnaires. Estimates of cortisol levels at four time points, the cortisol awakening response (CAR), and the diurnal cortisol slope (DCS) were estimated with a longitudinal mixed model that accounted for the non-linearity of cortisol levels across the day. Conventional farmers had significantly lower cortisol levels at waking than organic farmers (3.39 versus 3.86 ng ml−1), 30 min after waking (5.87 versus 6.96 ng ml−1), 6 h after waking (1.62 versus 1.88 ng ml−1), and lower diurnal cortisol slope (−2.26 versus −2.51 ng ml−1). Farmers who frequently applied herbicides (90th percentile of the number of spray days in the past 8 months) had significantly lower waking, 30 min after waking, 6 h after waking, bedtime and diurnal cortisol slopes compared with those with no spray days of herbicide in the past 8 months (organic and some of the conventional farmers). Those who frequently applied insecticides in the past 8 months had significantly lower bedtime levels and diurnal cortisol slopes, compared with those with no spray days of insecticide in the past 8 months. There were no significant differences in cortisol hormones between those who frequently applied fungicides and those who did not spray fungicides. Repeated pesticide use appears to be disrupting the HPA axis and depressing the normal diurnal cortisol rhythm among conventional Thai farmers.
Decline of Amateur Lepidoptera Collectors Threatens the Future of Specimen-Based Research
Authors: Fischer Erica E , Cobb Neil S , Kawahara Akito Y , Zaspel Jennifer M , Cognato Anthony I
Published: November 2020

Amateur butterfly and moth collectors in the United States have procured more Lepidoptera specimens than professional scientists. The advent of large government-supported database efforts has made a quantitative examination of the impact of amateur collecting of these insects possible. We reviewed trends in Lepidoptera collecting since 1800, using more than 1 million United States lepidopteran specimens that have been collected into public databases. Our findings show a steep rise in the collection of specimens after World War II, followed by a short plateau and sharp decline in the late 1990s. In contrast, the rate of observations submitted to database groups dramatically increased around 2005. Declining acquisition of Lepidoptera specimens may compromise critically important testing of contemporary and future ecological, conservation, and evolutionary hypotheses on a grand scale, particularly given documented declines in insect populations. We suggest that increasing collaboration between professional and community-based scientists could alleviate the decline in amateur-collected specimens.
Underlying mechanisms of development: pollen wall ontogeny inChloranthus japonicusand a reconsideration of pollen ontogeny in early-diverging lineages of angiosperms
Authors: Gabarayeva Nina I , Polevova Svetlana V , Grigorjeva Valentina V , Hiscock Simon J
Published: November 2020

Despite the large amount of knowledge accumulated, a precise understanding of the morphogenesis of the intricate and complex pollen walls (exines) is incomplete. A new factor (simple physico-chemical interactions) is shown to be involved in exine development. The stages of exine development in many species show remarkable similarity with successive micellar self-assembling mesophases of a colloidal system. Currently, > 100 genes have been reported to play a role in exine deposition, but nothing contradicts the view that specific patterns of exines are based on physico-chemical principles of space-filling operations taking place after genomic control of the concentrations of the source materials. On the examples of Chloranthus japonicus, magnoliids and other early-diverging angiosperms we show that exine development unfolds by two physico-chemical processes (phase separation and self-assembly) after genomic control, revealing an interplay between genomic and physical processes.
Fronto-temporal dementia risk gene TMEM106B has opposing effects in different lysosomal storage disorders
Authors: Perez-Canamas Azucena , Takahashi Hideyuki , Lindborg Jane A , Strittmatter Stephen M
Published: November 2020

TMEM106B is a transmembrane protein localized to the endo-lysosomal compartment. Genome-wide association studies have identified TMEM106B as a risk modifier of Alzheimer’s disease and frontotemporal lobar degeneration, especially with progranulin haploinsufficiency. We recently demonstrated that TMEM106B loss rescues progranulin null mouse phenotypes including lysosomal enzyme dysregulation, neurodegeneration and behavioural alterations. However, the reason whether TMEM106B is involved in other neurodegenerative lysosomal diseases is unknown. Here, we evaluate the potential role of TMEM106B in modifying the progression of lysosomal storage disorders using progranulin-independent models of Gaucher disease and neuronal ceroid lipofuscinosis. To study Gaucher disease, we employ a pharmacological approach using the inhibitor conduritol B epoxide in wild-type and hypomorphic Tmem106b−/− mice. TMEM106B depletion ameliorates neuronal degeneration and some behavioural abnormalities in the pharmacological model of Gaucher disease, similar to its effect on certain progranulin null phenotypes. In order to examine the role of TMEM106B in neuronal ceroid lipofuscinosis, we crossbred Tmem106b−/− mice with Ppt1−/−, a genetic model of the disease. In contrast to its conduritol B epoxide-rescuing effect, TMEM106B loss exacerbates Purkinje cell degeneration and motor deficits in Ppt1−/− mice. Mechanistically, TMEM106B is known to interact with subunits of the vacuolar ATPase and influence lysosomal acidification. In the pharmacological Gaucher disease model, the acidified lysosomal compartment is enhanced and TMEM106B loss rescues in vivo phenotypes. In contrast, gene-edited neuronal loss of Ppt1 causes a reduction in vacuolar ATPase levels and impairment of the acidified lysosomal compartment, and TMEM106B deletion exacerbates the mouse Ppt1−/− phenotype. Our findings indicate that TMEM106B differentially modulates the progression of the lysosomal storage disorders Gaucher disease and neuronal ceroid lipofuscinosis. The effect of TMEM106B in neurodegeneration varies depending on vacuolar ATPase state and modulation of lysosomal pH. These data suggest TMEM106B as a target for correcting lysosomal pH alterations, and in particular for therapeutic intervention in Gaucher disease and neuronal ceroid lipofuscinosis.
County-level Predictors of Coronavirus Disease 2019 (COVID-19) Cases and Deaths in the United States: What Happened, and Where Do We Go from Here?
Authors: McLaughlin John M , Khan Farid , Pugh Sarah , Angulo Frederick J , Schmitt Heinz-Josef , Isturiz Raul E , Jodar Luis , Swerdlow David L
Published: November 2020

Background

The United States has been heavily impacted by the coronavirus disease 2019 (COVID-19) pandemic. Understanding microlevel patterns in US rates of COVID-19 can inform specific prevention strategies.

Methods

Using a negative binomial mixed-effects regression model, we evaluated the associations between a broad set of US county-level sociodemographic, economic, and health status–related characteristics and cumulative rates of laboratory-confirmed COVID-19 cases and deaths between 22 January 2020 and 31 August 2020.

Results

Rates of COVID-19 cases and deaths were higher in US counties that were more urban or densely populated or that had more crowded housing, air pollution, women, persons aged 20–49 years, racial/ethnic minorities, residential housing segregation, income inequality, uninsured persons, diabetics, or mobility outside the home during the pandemic.

Conclusions

To our knowledge, this study provides results from the most comprehensive multivariable analysis of county-level predictors of rates of COVID-19 cases and deaths conducted to date. Our findings make clear that ensuring that COVID-19 preventive measures, including vaccines when available, reach vulnerable and minority communities and are distributed in a manner that meaningfully disrupts transmission (in addition to protecting those at highest risk of severe disease) will likely be critical to stem the pandemic.
Does compensation strategy instruction work? An action research study
Authors: Gül Peker Benâ , Erdemir Nihan
Published: November 2020

This collaborative action research study aimed to explore if and to what extent compensation strategy instruction (CSI) can improve the communicative competence of learners of EFL who mainly use L1 in classroom speaking activities. Designed by a university professor and an EFL instructor working at a state university in Turkey, the study was conducted with B1-level learners, aged 17–18, studying at the English Language Centre of the university. The study followed an action research intervention framework. In the second cycle of the intervention process, instruction in affective strategy use was provided in response to the emerging need for dealing with learners’ anxiety and stress. The findings indicate that learners can be taught how to use compensation strategies and that CSI may be useful for improving learners’ communicative competence in a speaking class. However, affective factors, if not addressed, can hinder learners’ effective use of compensation strategies.
Association between health literacy and colorectal cancer screening behaviors in adults in Northwestern Turkey
Authors: Pancar Nuket , Mercan Yeliz
Published: November 2020

Background

In this study, aimed to determine the frequency of participation in colorectal cancer (CRC) screenings, the factors affecting participation and the association between CRC screening behaviors and health literacy (HL).

Methods

This community-based cross-sectional study was carried out with 408 people residing in Kirklareli, a province in Northwestern Turkey, between August and November 2019.

Results

CRC screenings participation prevalence was 21.1%. Of them, 17.2% participated in fecal occult blood tests (FOBT) screenings, 7.6% participated in colonoscopy screenings, and 86.5% had inadequate or limited-problematic HL. According to the multivariate logistic regression analysis, the likelihood of not participating in CRC screenings was high in the participants who worked at a paid job (OR: 3.001, 95% CI: 1.018–8.850), who did not do any physical activity regularly (OR: 2.516, 95% CI: 1.251–5.060), who were not aware of the presence of an early diagnosis test for CRC (OR: 32.613, 95% CI: 13.338–79.742), who did not have a person having had CRC screening in their immediate environment (OR: 3.562, 95% CI: 1.752–7.240) and who had sufficient or excellent HL (OR: 3.324, 95% CI: 1.128–9.796). According to adjusted for some characteristics, there was no significant association between participation in CRC screenings and THLS-sub-dimensions and THLS-processes (P>0.05).

Conclusions

Participation in CRC screenings was low, and those with a high HL level were more likely not to participate in CRC screenings. Working status, knowledge and awareness levels affected the participation to CRC screenings. To encourage people to participate in screenings and to improve their HL, awareness-raising attempts for target groups should be increased.
Agrobacterium fabrum C58 involved nitrate reductase NapA and antisense RNA NorR to denitrify
Authors: Lecomte Solène , Nesme Xavier , Franzino Théophile , Villard Camille , Pivard Mariane , Vial Ludovic , Doré Jeanne , Hommais Florence , Haichar Feth el Zahar
Published: November 2020

Agrobacterium fabrum C58 is a plant-associated bacterium that is able to denitrify under anoxic conditions. The cluster of denitrification genes harbored by this strain has been well characterized. It includes nir and nor operons encoding nitrite and nitric oxide reductases, respectively. However, the reductase involved in nitrate reduction has not yet been studied and little information is available on denitrification regulators in A. fabrum C58. In this study, we aimed to (i) characterize the nitrate reductase, (ii) determine its role in A. fabrum C58 fitness and root colonization and (ii) reveal the contribution of small RNA on denitrification regulation. By constructing a mutant strain defective for napA, we demonstrated that the reduction of nitrate to nitrite was catalyzed by the periplasmic nitrate reductase, NapA. We evidenced a positive role of NapA in A. fabrum C58 fitness and suggested that A. fabrum C58 is able to use components exuded by plant roots to respire anaerobically. Here, we showed that NorR small RNA increased the level of norCBQ mRNA and a decrease of NorR is correlated with a decrease in N2O emission. Together, our results underscore the importance of understanding the denitrification pathway at the strain level in order to develop strategies to mitigate N2O production at the microbial community level.
The native acyltransferase-coding genes DGA1 and DGA2 affect lipid accumulation in Blastobotrys raffinosifermentans differently when overexpressed
Authors: Sanya Daniel Ruben Akiola , Onesime Djamila , Kunze Gotthard , Neuveglise Cécile , Crutz-Le Coq Anne-Marie
Published: November 2020

Blastobotrys raffinosifermentans is an ascomycetous yeast with biotechnological applications, recently shown to be an oleaginous yeast accumulating lipids under nitrogen limitation. Diacylglycerol acyltransferases (DGATs) act in the lipid storage pathway, in the last step of triacylglycerol biosynthesis. Two DGAT families are widespread in eukaryotes. We first checked that B. raffinosifermentans strain LS3 possessed both types of DGAT, and we then overexpressed the native DGAT-encoding genes, DGA1 and DGA2, separately or together. DGA2 (from the DGAT1 family) overexpression was sufficient to increase lipid content significantly in LS3, to up to 26.5% of dry cell weight (DCW), 1.6 times the lipid content of the parental strain (16.90% of DCW) in glucose medium under nitrogen limitation. By contrast, DGA1 (of the DGAT2 type) overexpression led to a large increase (up to 140-fold) in the amount of the corresponding transcript, but had no effect on overall lipid content relative to the parental strain. Analysis of the expression of the native genes over time in the parental strain revealed that DGA2 transcript levels quadrupled between 8 and 24 h in the N-limited lipogenic medium, whereas DGA1 transcript levels remained stable. This survey highlights the predominant role of the DGAT1 family in lipid accumulation and demonstrates the suitability of B. raffinosifermentans for engineering for lipid production.
Factors associated with wide variation in clinical litigation rates across acute NHS trusts in England: a cross-sectional analysis
Authors: Griggs Beverley , Childs Tristan , Birkinshaw Jamie , Badrinath Padmanabhan
Published: November 2020

Objective

Identify organizational factors associated with high clinical litigation rates among acute National Health Service (NHS) trusts in England.

Design

Cross-sectional analysis using routine data.

Setting

NHS trusts in England.

Participants

A total of 235 NHS trusts used the NHS Clinical Negligence Scheme in 2016–17. Ninety-seven trusts (41.3%) with no maternity services, 2 (0.9%) providing specialized services and 3 (1.2%) without clinical negligence claims were excluded. Hence, the remaining 133 trusts (56.6%) were included.

Intervention(s)

None.

Main Outcome Measures

Rate of clinical litigation by trust per 100 000 occupied bed days.

Results

The mean rate of clinical litigation was 25.4 per 100 000 occupied bed days. In univariable analyses, higher values of summary hospital-level mortality indictor, staff sickness, written complaints, patient safety incidents and being in the North of England led to increased clinical litigation rates. Conversely, higher patient admissions, NHS Staff Survey overall engagement score and occupied bed days led to decreased clinical litigation rates. In the multivariable model, factors associated with increased clinical litigation rates were as follows: summary mortality hospital-level indicator (SHMI) (0.9 increase in litigation rate per 0.05 increase in SHMI; P = 0.012); new written complaints (0.62 increase per 50 complaints higher; P < 0.001); located in the North of England compared to London (5.22 higher; P < 0.001). Conversely, a higher number of occupied bed days (−0.64 change per 50 000 days higher; P = 0.007) was associated with lower clinical litigation rates.

Conclusions

This study identified organizational factors associated with clinical litigation, which will be of interest to clinicians and the NHS. This research also highlights areas for further investigation.
The Interaction between Hb A1C and Selected Genetic Factors in the African American Population in the USA
Authors: Harris Neil S , Weaver Kaitlin D , Beal Stacy G , Winter William E
Published: November 2020

Background

The global prevalence of diabetes mellitus has been growing in recent decades and the complications of longstanding type 2 diabetes continue to place a burden on healthcare systems. The hemoglobin A1c (Hb A1c) content of the blood is used to assess an individual’s degree of glycemic control averaged over 2 to 3 months. In the USA, diabetes is the seventh leading cause of death. Black, indigenous, people of color (BIPOC) are disproportionately affected by diabetes compared to non-Hispanic whites. There are many reports of interaction of Hb A1c and hematologic conditions that have a high prevalence in the Black population; some of these effects are contradictory and not easily explained. This review attempts to document and categorize these apparently disparate effects and to assess any clinical impact.

Methods

Hb A1C can be determined by a variety of techniques including cation-exchange chromatography, electrophoresis, immunoassays, and affinity chromatography. The amount of Hb A1c present in a patient specimen depends not only on blood glucose but is strongly influenced by erythrocyte survival and by structural variations in the globin chains. Sickling hemoglobinopathies are well-represented in the USA in African Americans and the effects of these hemoglobin disorders as well as G6PD deficiency is examined.

Conclusion

Hb A1c measurement should always be performed with a cautious approach. The laboratory scientist should be aware of possible pitfalls in unquestioningly determining Hb A1c without a consideration of hematologic factors, both inherited and acquired. This presents a challenge as often times, the laboratory is not aware of the patient’s race.
Speaking up about patient-perceived serious visit note errors: Patient and family experiences and recommendations
Authors: Lam Barbara D , Bourgeois Fabienne , Dong Zhiyong J , Bell Sigall K
Published: November 2020

Background

Open notes invite patients and families to read ambulatory visit notes through the patient portal. Little is known about the extent to which they identify and speak up about perceived errors. Understanding the barriers to speaking up can inform quality improvements.

Objective

To describe patient and family attitudes, experiences, and barriers related to speaking up about perceived serious note errors.

Methods

Mixed method analysis of a 2016 electronic survey of patients and families at 2 northeast US academic medical centers. Participants had active patient portal accounts and at least 1 note available in the preceding 12 months.

Results

6913 adult patients (response rate 28%) and 3672 pediatric families (response rate 17%) completed the survey. In total, 8724/9392 (93%) agreed that reporting mistakes improves patient safety. Among 8648 participants who read a note, 1434 (17%) perceived ≥1 mistake. 627/1434 (44%) reported the mistake was serious and 342/627 (56%) contacted their provider. Participants who self-identified as Black or African American, Asian, “other,” or “multiple” race(s) (OR 0.50; 95% CI (0.26,0.97)) or those who reported poorer health (OR 0.58; 95% CI (0.37,0.90)) were each less likely to speak up than white or healthier respondents, respectively. The most common barriers to speaking up were not knowing how to report a mistake (61%) and avoiding perception as a “troublemaker” (34%). Qualitative analysis of 476 free-text suggestions revealed practical recommendations and proposed innovations for partnering with patients and families.

Conclusions

About half of patients and families who perceived a serious mistake in their notes reported it. Identified barriers demonstrate modifiable issues such as establishing clear mechanisms for reporting and more challenging issues such as creating a supportive culture. Respondents offered new ideas for engaging patients and families in improving note accuracy.
Patients’ Preferences for 3 Months vs 6 Months of Adjuvant Chemotherapy for Colon Cancer
Authors: Blinman Prunella , Martin Andrew , Jefford Michael , Goldstein David , Boadle David , Morris Michelle , Tebbutt Niall , Aiken Christine , Harkin Andrea , Segelov Eva , Haydon Andrew , Iveson Tim , Stockler Martin R
Published: November 2020

Background

SCOT was an international, randomized phase 3 trial of 3 months vs 6 months of adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine in patients with colorectal cancer. We sought patients’ preferences for 3 months vs 6 months of adjuvant chemotherapy in the SCOT trial.

Methods

SCOT participants from Australia and New Zealand completed a validated questionnaire (at 3 and 18 months) to elicit the minimum survival benefits judged necessary to make an extra 3 months of adjuvant chemotherapy worthwhile, based on their experience. Standardized hypothetical scenarios used the following baseline survivals (with 3 months of chemotherapy): life expectancies (LE) of 5 years and 15 years and 5-year survival rates (5YS) of 65% and 85%.

Results

Of the 160 participants, 82 were assigned 3 months adjuvant chemotherapy, and 78 were assigned 6 months. Adjuvant chemotherapy was FOLFOX in 121 (75.6%) and XELOX in 39 (24.4%). Preferences varied substantially and did not differ according to treatment group. The median survival benefits judged necessary to make the extra 3 months of chemotherapy worthwhile were an extra 3 years beyond a LE of 5 years; 3 years beyond a LE of 15 years; 15% beyond a 5YS of 65%; and 5% beyond a 5YS of 85%. Preferences were similar at 3 months and 18 months. Preferences were not predicted by participants’ baseline characteristics.

Conclusion

Preferences varied substantially, and the benefits many required to warrant an extra 3 months of adjuvant chemotherapy were larger than the benefits of an extra 3 months of chemotherapy calculated in the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) meta-analysis.
The structure and relations of banking systems: the UK experience and the challenges of ‘levelling-up’
Authors: Mayer Colin , McCann Philip , Schumacher Jacob
Published: November 2020

A decentralized banking system is marked by geographical dispersion of banks with close proximity of banks to their borrowers and strong long-term relationships between banks and their borrowers based on soft, tacit, as well as hard, codified information. It is important for promoting the development of small and medium-sized enterprises (SMEs) particularly in regional locations. In contrast, the UK has a highly centralized, concentrated banking system with weak relationships between banks and their borrowers. This has contributed to the high degree of regional disparity across the UK. The programme of ‘levelling up’ regions will require a more decentralized banking system. The cases of Germany, the US, and the Swedish bank Handelsbanken illustrate the advantages of decentralized banking. They also have important lessons for the way in which decentralized banking systems should be structured and organized and, in particular, for the regulatory arrangements that are conducive to their satisfactory functioning and avoidance of pitfalls to which they can otherwise be prone.
Considering the Feasibility, Tolerability, and Safety of High-Intensity Interval Training as a Novel Treatment for Patients With Intermittent Claudication
Authors: Pymer Sean , Ibeggazene Saïd , Palmer Joanne , Smith George E. , Harwood Amy E. , Carroll Sean , Ingle Lee , Chetter Ian C.
Published: November 2020

Purpose:

This study assessed the feasibility, tolerability, safety, and potential efficacy of a novel, 6-wk, high-intensity interval training (HIIT) program for patients with intermittent claudication (IC).

Methods:

Patients referred to a usual-care supervised exercise program were invited to undertake a HIIT program. All recruited patients performed a baseline cardiopulmonary exercise test (CPX) to inform their exercise prescription. HIIT involved 10, 1-min high-intensity cycling intervals interspersed with 1-min recovery intervals, performed 3 d/wk for 6 wk. Outcomes included feasibility, tolerability, safety, walking distance, and quality of life.

Results:

A total of 144 patients with IC were referred, 95 met initial eligibility criteria (66%) and 30 (32%) were recruited for HIIT, of which 15 (50%) completed. Of the recruited patients, 90% were on optimal medical therapy and 40% had concomitant cardiac, cerebrovascular, and/or respiratory disease. Patients who completed the program attended 100% of the sessions and one serious adverse event was recorded. Improvements in walking distances and quality of life were observed. Following recruitment of the first 20 patients, the inclusion criteria were refined on the basis of CPX, leading to improved completion rates.

Conclusions:

This study provides preliminary findings indicating that patients with IC can complete a short-term HIIT program. We provide very early evidence that HIIT may be safe and well-tolerated. In addition, walking distances seem to improve following HIIT. After a small change in the exclusion criteria, the intervention and inclusion/exclusion criteria now seem appropriate for this population, meaning further research to evaluate HIIT in patients with IC is warranted.
Predictors of Exercise Maintenance 6 Months After Comprehensive Cardiac Rehabilitation
Authors: Ghisi Gabriela Lima de Melo , Alavinia Mohammad , Aultman Crystal , Rouleau Fanny , Ross Marie-Kristelle , Dufour-Doiron Monique , Belliveau Sylvie L. , Brideau Jean-René , Oh Paul
Published: November 2020

Purpose:

The objectives of this study were (1) to assess the effects of a comprehensive education intervention on maintenance of knowledge, exercise behavior, heart-healthy food intake, self-efficacy, and health literacy 6 mo after comprehensive cardiac rehabilitation (CR), and (2) to identify predictors of exercise maintenance 6 mo after comprehensive CR.

Methods:

A prospective longitudinal study was conducted to test the effects of a structured educational curriculum in three CR programs in Canada. Participants completed surveys pre-, post-CR and 6 mo post-discharge to assess knowledge, heart-healthy food intake, self-efficacy, and health literacy. Exercise behavior was measured by number of steps/d using a pedometer.

Results:

One hundred twenty participants completed the final survey. Increases in disease-related knowledge and self-efficacy, as well as behavior changes (increases in exercise and heart-healthy food intake), were achieved in comprehensive CR and sustained 6 mo post-program. Exercise maintenance was predicted by changes in heart-healthy food intake, self-efficacy, health literacy, and exercise-related knowledge.

Conclusions:

In this three-site study focusing on patient education for CR patients in Canada, the benefits of an education intervention in maintaining knowledge, exercise, healthy food intake, and self-efficacy were supported.
Emergence of ciprofloxacin-resistant Neisseria meningitidis B from asymptomatic carriers during an outbreak in Peru, 2017
Authors: Juscamayta-López Eduardo , Valdivia Faviola , Morales Sara , Donaires Luis Fernando , Fiestas-Solórzano Victor , Oré Marianela , Pachas Paul , León-Janampa Nancy , Gavilán Ronnie
Published: November 2020

Asymptomatic carriers are a likely source of transmission of

Neisseria meningitidis

to close contacts who are placed at a higher risk for invasive meningococcal disease (IMD). Although

N. meningitidis

ciprofloxacin-resistance is rare, there have been an increase in the reports of resistant isolates mainly in patients diagnosed with IMD, and little is known about the

N. meningitidis

ciprofloxacin-resistance in the carrier populations. We performed a pharyngeal carriage study during a 2017 military setting outbreak in Peru, caused by a ciprofloxacin-resistant

N. meningitidis

B. The isolates analysed came from two hospitalized cases and six asymptomatic carriers. Whole-genome sequence-based analysis was performed and showed that strains carrying the Thr91Ile mutation, in the gene encoding for subunit A of DNA gyrase (gyrA), were responsible for the fluoroquinolone resistance (MICs ≥0.256 µg ml−1) and were closely related to highly virulent strains from France, Norway and the UK. Phylogenetic analysis of the gyrA gene revealed that likely these Peruvian isolates acquired resistance through horizontal gene transfer from

Neisseria lactamica

. Our study provides evidence for the emergence and propagation of ciprofloxacin-resistant

N. meningitidis

B from asymptomatic carriers, and recommends the introduction of serogroup B vaccines for high-risk populations.
Continued Age Shift of Confirmed Positive COVID-19 Incidence Over Time to Children and Young Adults: Washington State March - August 2020
Authors: Malmgren Judith , Guo Boya , Kaplan Henry G.
Published: November 2020

Background

As the coronavirus (COVID-19) epidemic passed the initial infection peak in Washington State, phased re-opening lifted stay-at-home orders and restrictions leading to increased non-essential work, social activities and gathering, especially among younger persons.

Methods

A longitudinal cohort analysis of Washington State Department of Health COVID-19 confirmed case age distribution 1) March-April 2020 (N=13,934) and 2) March-August 2020 (N=76,032) for proportional change over time using chi square tests for significance.

Results

From March 1st to April 19, 2020 COVID-19 case positive age distribution shifted with a 10% decline in cases age 60 years and older and a 20% increase in age 0-19/20-39 years (chi-square = 223.10, p <.001). Number of cases over the eight-week analysis period were 0-19 years n = 515, 20-39 years n = 4078, 40-59 years n =4788, 60-79 years n = 3221, 80+ years n = 1332. After the peak (March 22, 2020), as incidence declined in older age groups, the combined percentage of cases age 0-19 and 20-39 increased from 20% to 40% of total cases. During this time testing expanded with more testing among older age groups while case positivity shifted young. Percent positive cases by age through August 2020 increased to a consistent average of 60% less than age 40 [age 0-19 increased to 19% (N = 10257), age 20-39 increased to 42% (N = 30215)].

Conclusions

An increased share of COVID-19 incidence among children (age 0-19) and young adults (age 20-39) indicates their elevated role in propagating the epidemic by creating a reservoir of disease with risk of spillovers to more vulnerable older persons and those with comorbid conditions. Media savvy and age appropriate COVID-19 messaging may increase mitigation compliance among these less vulnerable, more mobile and lower priority vaccination age groups. As vaccines become available, mitigation will continue to be a priority to reduce overall population incidence.
Relation of Quantitative Histologic and Radiologic Breast Tissue Composition Metrics with Invasive Breast Cancer Risk
Authors: Abubakar Mustapha , Fan Shaoqi , Bowles Erin Aiello , Widemann Lea , Duggan Máire A. , Pfeiffer Ruth M. , Falk Roni T. , Lawrence Scott , Richert-Boe Kathryn , Glass Andrew G. , Kimes Teresa M. , Figueroa Jonine D. , Rohan Thomas E. , Gierach Gretchen L.
Published: November 2020

Purpose

Benign breast disease (BBD) is a strong breast cancer risk factor but identifying patients that might develop invasive breast cancer remains a challenge.

Methods

By applying machine-learning to digitized H&E-stained biopsies and computer-assisted thresholding to mammograms obtained circa BBD diagnosis, we generated quantitative tissue composition metrics and determined their association with future invasive breast cancer diagnosis. Archival breast biopsies and mammograms were obtained for women (18-86 years) in a case-control study, nested within a cohort of 15,395 BBD patients from Kaiser Permanente Northwest (1970-2012), followed through mid-2015. Cases (n=514) who developed incident invasive breast cancer and controls (n=514) were matched on BBD diagnosis age and plan membership duration.

Results

Increasing epithelial area on the BBD biopsy was associated with increasing breast cancer risk [Odds ratio(OR) 95% confidence interval(CI) Q4 vs Q1=1.85(1.13-3.04);Ptrend=0.02]. Conversely, increasing stroma was associated with decreased risk in non-proliferative, but not proliferative, BBD (Pheterogeneity=0.002). Increasing epithelium-to-stroma proportion [OR(95%CI)Q4 vs Q1=2.06(1.28-3.33);Ptrend=0.002] and percent mammographic density (MBD) [OR(95%CI)Q4 vs Q1=2.20(1.20-4.03);Ptrend=0.01] were independently and strongly predictive of increased breast cancer risk. In combination, women with high epithelium-to-stroma proportion/high MBD had substantially higher risk than those with low epithelium-to-stroma proportion/low MBD [OR(95%CI)=2.27(1.27-4.06);Ptrend=0.005], particularly among women with non-proliferative [Ptrend=0.01] versus proliferative [Ptrend=0.33] BBD.

Conclusion

Among BBD patients, increasing epithelium-to-stroma proportion on BBD biopsies and percent MBD at BBD diagnosis were independently and jointly associated with increasing breast cancer risk. These findings were particularly striking for women with non-proliferative disease (comprising ∼70% of all BBD patients), for whom relevant predictive biomarkers are lacking.
Artificial intelligence-enabled event adjudication: estimating delayed cardiovascular effects of respiratory viruses
Authors: Goto Shinichi , Homilius Max , John Jenine E. , Truslow James G. , Werdich Andreas A. , Blood Alexander J. , Park Brian H. , MacRae Calum A. , Deo Rahul C.
Published: November 2020

Healthcare systems ideally should be able to draw lessons from historical data, including whether common exposures are associated with adverse clinical outcomes. Unfortunately, structured clinical data, such as encounter diagnostic codes in electronic health records, suffer from multiple limitations and biases, limiting effective learning. We hypothesized that a machine learning approach to automate ascertainment of clinical events and disease history from medical notes would improve upon using structured data and enable the estimation of real-world risks. We sought to test this approach to address a timely goal: estimating the delayed risk of adverse cardiovascular events (i.e. after the index infection) in patients infected with respiratory viruses. Using 4,151 cardiologist-labeled notes as gold standard, we trained a series of neural network models to automate event adjudication for heart failure hospitalization, acute coronary syndrome, stroke, and coronary revascularization and to identify past medical history for heart failure. Though performance varied by task, in nearly all cases, our models surpassed the use of structured data in terms of sensitivity for a given specificity level and enabled principled evaluation of classification thresholds, which is typically impossible to do with diagnostic codes. Deploying our models on more than 17 million notes for 267,596 patients across an extensive integrated delivery network, we found that patients infected with respiratory syncytial virus had a 23% increased risk of delayed heart failure hospitalization over a subsequent 4-year period compared with propensity-score matched patients who had the same test but with negative results (p = 0.003, log-rank). In contrast, we found no such increased risk in patients with a positive influenza viral test compared with a negative test (rate ratio 0.98, p = 0.71). We conclude that convolutional neural network-based models enable accurate clinical labeling at scale, thereby unlocking timely insights from unstructured clinical data.
Clinical subgroup clustering analysis in a systemic lupus erythematosus cohort from Western Pennsylvania
Authors: Coit Patrick , Ruffalo Lacy , Sawalha Amr H
Published: November 2020

Objective

Systemic lupus erythematosus (SLE) is a complex heterogenous autoimmune disease that can affect multiple organs. We performed clinical clustering analysis to describe a lupus cohort from the University of Pittsburgh Medical Center.

Methods

A total of 724 patients who met the ACR classification criteria for SLE were included in this study. Clustering was performed using the ACR classification criteria and the partitioning around medoid method. Correlation analysis was performed using the Spearman’s Rho test.

Results

Patients with SLE in our cohort identify 3 district clinical disease subsets. Patients in Cluster 1 were significantly more likely to develop renal and hematologic involvement, and had overrepresentation in African-American and male lupus patients. Clusters 2 and 3 identified a milder disease, with a significantly less likelihood of organ complications. Patients in Cluster 2 are characterized by malar rash and photosensitivity, while patients in Cluster 3 are characterized by oral ulcers which is present in ∼90% of patients within this cluster. The presence of photosensitivity or oral ulcers appears to be protective against the development of lupus nephritis in our cohort.

Conclusions

We describe a large cohort of SLE from Western Pennsylvania and identify 3 distinct clinical disease subgroups. Clustering analysis might help to better manage and predict disease complications in heterogenous diseases like lupus.