bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral blood and bronchoalveolar leukocyte profile in lung transplant recipients and their changes according to immunosuppressive regimen: A single‐center experience
Authors: Jáky‐Kováts Zsuzsanna , Vámos Melinda , Komlósi Zsolt István , Bikov András , Madurka Ildikó , Szűcs Gergő , Müller Veronika , Bohács Anikó
Published: July 2022

Background

After lung transplantation (LuTX), lower respiratory tract infections (LRTI) and acute cellular rejection (ACR) are associated with changes in peripheral blood and bronchoalveolar lavage fluid mononuclear cell profile (PBMC and BALIC). PBMC is also influenced by immunosuppressive regimen and its changes with postoperative time. First‐year PBMC and BALIC changes were evaluated in this study with rabbit anti‐thymocyte globulin (ATG) and alemtuzumab (AL) induction therapy.

Methods

In total, 64 LuTX recipients were included, 53 of them received AL and 11 ATG as induction therapy. PBMC and BALIC were examined routinely and in cases suspicious of infection and/or rejection. A PBMC‐ and BALIC‐based algorithm for infection and rejection prediction was also tested.

Results

In the AL group, peripheral blood lymphocyte and basophil cell numbers were significantly reduced, while the neutrophil cell number elevation during LRTI was significantly higher compared to the control. Early postoperative measurements showed a lower BALIC lymphocyte count. The algorithm had 17% sensitivity and 94% specificity for ACR in all patients and 33% sensitivity and 95% specificity for ACR with coexisting LRTI.

Conclusion

BALIC is not significantly influenced by the immunosuppressive regimen. PBMC‐ and BALIC‐based algorithm may improve the differential diagnosis of ACR.
Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy
Authors: Luo Lisha , Deng Shuanglinzi , Tang Wei , Hu Xinyue , Yin Feifei , Ge Huan , Tang Jiale , Liao Zhonghua , Feng Juntao , Li Xiaozhao , Mo Biwen
Published: July 2022

Background

Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion.

Methods

Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real‐time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions.

Results

CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL‐1β, IL‐17, IL‐27, and IFN‐γ, in TPE were much higher than in other pleural effusions. Moreover, CD14+CD16++ nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14++CD16+ intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1‐CX3CR1 axis‐mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN‐γ expression in TPE. Higher expression of cytokines (IL‐1β, IL‐17, IL‐27, and IFN‐γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion.

Conclusions

CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.
Simultaneous quantification of dasatinib, nilotinib, bosutinib, and ponatinib using high‐performance liquid chromatography–Photodiode array detection
Authors: Yokoyama Yuta , Nozawa Eiji , Morita Miho , Ishikawa Emi , Mori Takehiko , Sakurai Masatoshi , Kikuchi Taku , Matsuki Eri , Yamazaki Rie , Kataoka Keisuke , Jibiki Aya , Kawazoe Hitoshi , Suzuki Sayo , Nakamura Tomonori
Published: July 2022

Background

Dasatinib, nilotinib, and bosutinib, second‐generation tyrosine kinase inhibitors (TKIs), and ponatinib, a third‐generation TKI, are approved pharmaceuticals used in the treatment of chronic myeloid leukemia (CML). Although liquid chromatography‐tandem mass spectrometry assays for simultaneous quantification of the four TKIs in human serum have been reported in the literature, a high‐performance liquid chromatography (HPLC) assay that simultaneously quantifies these compounds has not yet been developed. This study aims to establish and validate an efficient HPLC analytical method using a photodiode array (PDA) detector for the simultaneous quantification of the four TKIs.

Methods

Calibration standards were prepared by serial dilution of serum samples containing the four TKIs, followed by solid‐phase extraction. The four TKIs were eluted in order within 10 min using a binary HPLC gradient system.

Results

The calibration ranges were 2–500 ng/ml for dasatinib, 100–5000 ng/ml for nilotinib, and 10–500 ng/ml for bosutinib and ponatinib. Intra‐day and inter‐day precision and accuracy values were found to be in accordance with the U.S. Food and Drug Administration guidelines. The recovery rates were 92.9%–96.0%, 80.7%–86.1%, 91.6%–99.0%, and 86.4%–92.6% for dasatinib, nilotinib, bosutinib, and ponatinib, respectively.

Conclusion

To the best of our knowledge, this is the first report of an HPLC‐PDA analytical method that allows efficient simultaneous quantification of the four TKIs in the serum of patients with CML. We believe that the method developed herein can improve the efficiency of therapeutic drug monitoring in patients with CML in clinical practice.
The influence of multiple frailty profiles on institutionalization and all‐cause mortality in community‐living older adults
Authors: Lee Yunhwan , Kim Eunsaem , Yun Jihye , Chuck Kumban Walter
Published: July 2022

Background

Frailty in older adults is associated with adverse geriatric outcomes. Physical frailty is often accompanied by problems in the cognitive, psychological, and social domains. This study investigated the ability of physical frailty combined with other health domains to predict institutionalization and mortality.

Methods

A national sample of 9171 Koreans aged 65 years or older were surveyed at baseline in 2008 and 3 year follow‐up. Those who were prefrail or frail according to the Fried criteria were conceived to have physical frailty. Psychological frailty, cognitive frailty, and social frailty were defined as having depressive symptoms, cognitive impairment, and social vulnerabilities, respectively, in addition to physical frailty. Using Cox proportional hazards and competing‐risks regression, the risk of mortality and institutionalization by the number and profiles of different frailty domains was analysed.

Results

At baseline, the 9171 participants were aged 73.1 (±6.8) years on average (median: 72, range: 65 to 103), and 59.2% were women. Multidomain frailty was highly prevalent (49.3%), with 6.1% concurrently displaying frailty in all four domains (mixed frailty). The risk of negative health outcomes increased with frailty in a higher number of domains with a subhazard ratio (SHR) of 3.48 (95% confidence interval [CI]: 1.83, 6.62; P < 0.001) for institutionalization and a hazard ratio (HR) of 3.95 (95% CI: 2.62, 5.93; P < 0.001) for mortality among those presenting mixed frailty. Psychological frailty (depressive symptoms combined with physical frailty) was strongly predictive of institutionalization (SHR = 2.85; 95% CI: 1.45, 5.59; P = 0.002) and mortality (HR = 2.47; 95% CI: 1.61, 3.78; P < 0.001). When combined with physical frailty and either depressive symptoms or social vulnerabilities, cognitive impairment also exhibited a significantly elevated risk of negative events. Physical frailty alone was not a strong predictor of adverse events, especially for mortality (HR = 1.13; 95% CI: 0.77, 1.67; P = 0.53).

Conclusions

Co‐occurrence of physical frailty with other domains is common in late life. The presence of frailty in multiple domains raises the risk of adverse outcomes, with the effects varying by multidimensional profiles.
Frameworks and measures for HIV‐related internalized stigma, stigma and discrimination in healthcare and in laws and policies: a systematic review
Authors: Ferguson Laura , Gruskin Sofia , Bolshakova Maria , Yagyu Sachi , Fu Ning , Cabrera Nicky , Rozelle Mary , Kasoka Kasoka , Oraro‐Lawrence Tessa , Stackpool‐Moore Lucy , Motala Aneesa , Hempel Susanne
Published: July 2022

Introduction

There is strong global commitment to eliminate HIV‐related stigma, and work in this area continues to evolve. Wide variation exists in frameworks and measures used.

Methods

Building on the existing knowledge syntheses, we carried out a systematic review to identify frameworks and measures aiming to understand or assess internalized stigma, stigma and discrimination in healthcare, and in law and policy. The review addressed two questions: Which conceptual frameworks have been proposed to assess internalized stigma, stigma and discrimination experienced in healthcare settings, and stigma and discrimination entrenched in national laws and policies? Which measures of these different types of stigma and discrimination have been proposed and what are their descriptive properties? Searches, completed on 6 May 2021, cover publications from 2008 onwards. The review is registered in PROSPERO (CRD42021249348), the protocol incorporated stakeholder input, and the data are available in the Systematic Review Data Repository.

Results and discussion

Sixty‐nine frameworks and 50 measures met the inclusion criteria. Critical appraisal figures and detailed evidence tables summarize these resources. We established a compendium of frameworks and a catalogue of measures of HIV‐related stigma and discrimination. Seventeen frameworks and 10 measures addressed at least two of our focus domains, with least attention to stigma and discrimination in law and policy. The lack of common definitions and variability in scope and structure of HIV‐related frameworks and measures creates challenges in understanding what is being addressed and measured, both in relation to stigma and efforts to mitigate or reduce its harmful effects. Having comparable data is essential for tracking change over time within and between interventions.

Conclusions

This systematic review provides an evidence base of current understandings of HIV‐related stigma and discrimination and how further conceptual clarification and increased adaptation of existing tools might help overcome challenges across the HIV care continuum. With people living with HIV at the centre, experts from different stakeholder groups could usefully collaborate to guide a more streamlined approach for the field. This can help to achieve global targets and understand, measure and help mitigate the impact of different types of HIV‐related stigma on people's health and quality of life.
Telling the story of intersectional stigma in HIV‐associated Kaposi's sarcoma in western Kenya: a convergent mixed‐methods approach
Authors: Collier Sigrid , Singh Rhea , Semeere Aggrey , Byakwaga Helen , Laker‐Oketta Miriam , McMahon Devon E. , Chemtai Linda , Grant Merridy , Butler Lisa , Bogart Laura , Bassett Ingrid V. , Kiprono Samson , Maurer Toby , Martin Jeffrey , Busakhala Naftali , Freeman Esther E.
Published: July 2022

Introduction

The experience of stigma can be multifaceted for people with HIV and cancer. Kaposi's sarcoma (KS), one of the most common HIV‐associated cancers in sub‐Saharan Africa, often presents with visible skin lesions that may put people at risk for stigmatization. In this way, HIV‐associated KS is unique, as people with KS can experience stigma associated with HIV, cancer, and skin disease simultaneously. The aim of this study is to characterize the intersectionality of HIV‐related, cancer‐related and skin disease‐related stigma in people living with HIV and KS.

Methods

We used a convergent mixed‐methods approach nested within a longitudinal study of people with HIV‐associated KS in western Kenya. Between February 2019 and December 2020, we collected quantitative surveys among all participants and conducted semi‐structured interviews among a purposive sample of participants. Quantitative surveys were adapted from the abridged Berger HIV Stigma Scale to assess overall stigma, HIV‐related stigma, cancer‐related stigma, and skin disease‐related stigma. Qualitative data were coded using stigma constructs from the Health Stigma and Discrimination Framework.

Results

In 88 semi‐structured interviews, stigma was a major barrier to KS diagnosis and treatment among people with HIV‐associated KS. Participant's stories of stigma were dominated by HIV‐related stigma, more than cancer‐related or skin disease‐related stigma. However, quantitative stigma scores among the 117 participants were similar for HIV‐related (Median: 28.00; IQR: 28.0, 34.0), cancer‐related (Median: 28.0; IQR: 28.0, 34.8), and skin disease‐related stigma (Median: 28.0; IQR: 27.0, 34.0). In semi‐structured interviews, cancer‐related and skin disease‐related stigma were more subtle contributors; cancer‐related stigma was linked to fatalism and skin‐related stigma was linked to visible disease. Participants reported resolution of skin lesions contributed to lessening stigma over time; there was a significant decline in quantitative scores of overall stigma in time since KS diagnosis (adjusted β = –0.15, p <0.001).

Conclusions

This study highlights the role mixed‐method approaches can play in better understanding stigma in people living with both HIV and cancer. While HIV‐related stigma may dominate perceptions of stigma among people with KS in Kenya, intersectional experiences of stigma may be subtle, and quantitative evaluation alone may be insufficient to understand intersectional stigma in certain contexts.
“I was still very young”: agency, stigma and HIV care strategies at school, baseline results of a qualitative study among youth in rural Kenya and Uganda
Authors: Johnson‐Peretz Jason , Lebu Sarah , Akatukwasa Cecilia , Getahun Monica , Ruel Theodore , Lee Joi , Ayieko James , Mwangwa Florence , Owino Lawrence , Onyango Anjeline , Maeri Irene , Atwine Frederick , Charlebois Edwin D. , Bukusi Elizabeth A. , Kamya Moses R. , Havlir Diane V. , Camlin Carol S.
Published: July 2022

Introduction

Adolescents and young adults living with HIV (AYAH) have the lowest rates of retention in HIV care and antiretroviral therapy (ART) adherence, partly due to the demands of school associated with this life stage, to HIV‐related stigma and to fears of serostatus disclosure. We explore the implications of school‐based stigma and disclosure on the development of agency during a critical life stage in rural Kenya and Uganda.

Methods

We conducted a qualitative study in the baseline year of the SEARCH Youth study, a combination intervention using a life‐stage approach among youth (15–24 years old) living with HIV in western Kenya and southwestern Uganda to improve viral load suppression and health outcomes. We conducted in‐depth, semi‐structured interviews in 2019 with three cohorts of purposively selected study participants (youth [n = 83], balanced for sex, life stage and HIV care status; recommended family members of youth [n = 33]; and providers [n = 20]). Inductive analysis exploring contextual factors affecting HIV care engagement revealed the high salience of schooling environments.

Results

Stigma within school settings, elicited by non‐consensual serostatus disclosure, medication schedules and clinic appointments, exerts a constraining factor around which AYAH must navigate to identify and pursue opportunities available to them as young people. HIV status can affect cross‐generational support and cohort formation, as AYAH differ from non‐AYAH peers because of care‐related demands affecting schooling, exams and graduation. However, adolescents demonstrate a capacity to overcome anticipated stigma and protect themselves by selectively disclosing HIV status to trusted peers and caregivers, as they develop a sense of agency concomitant with this life stage. Older adolescents showed greater ability to seek out supportive relationships than younger ones who relied on adult caregivers to facilitate this support.

Conclusions

School is a potential site of HIV stigma and also a setting for learning how to resist such stigma. School‐going adolescents should be supported to identify helpful peers and selectively disclose serostatus as they master decision making about when and where to take medications, and who should know. Stigma is avoided by fewer visits to the clinic; providers should consider longer refills, discreet packaging and long‐acting, injectable ART for students.
Tackling structural stigma: a systems perspective
Authors: Brown Graham , Reeders Daniel , Cogle Aaron , Allan Brent , Howard Chris , Rule John , Chong Susan , Gleeson Deborah
Published: July 2022

Introduction

Structural stigma in the global HIV response is a “moving target” that constantly evolves as the epidemic changes. Tackling structural stigma requires an understanding of the drivers and facilitators of stigma in complex community, policy and health systems. In this paper, we present findings from a study adopting a systems perspective to understand how to tackle structural stigma via the Meaningful Involvement of People with HIV/AIDS (MIPA), while highlighting the challenges in demonstrating peer leadership from people living with HIV (PLHIV).

Methods

Through a long‐term ongoing community‐research collaboration (2015–2023), the study applied systems thinking methods to draw together the insights of over 90 peer staff from 10 Australian community and peer organizations. We used hypothetical narratives, affinity methods and causal loop diagrams to co‐create system maps that visualize the factors that influence the extent to which peer leadership is expected, respected, sought‐out and funded in the Australian context. We then developed draft indicators of what we should see happening when PLHIV peer leadership and MIPA is enabled to challenge structural stigma.

Results

Participants in the collaboration identified the interactions at a system level, which can enable or constrain the quality and influence of PLHIV peer leadership. Participants identified that effective peer leadership is itself affected by structural stigma, and peer leaders and the programmes that support and enable peer leadership must navigate a complex network of causal pathways and strategic pitfalls. Participants identified that indicators for effective PLHIV peer leadership in terms of engagement, alignment, adaptation and influence also required indicators for policy and service organizations to recognize their own system role to value and enable PLHIV peer leadership. Failing to strengthen and incorporate PLHIV leadership within broader systems of policy making and health service provision was identified as an example of structural stigma.

Conclusions

Incorporating PLHIV leadership creates a virtuous cycle, because, as PLHIV voices are heard and trusted, the case for their inclusion only gets stronger. This paper argues that a systems perspective can help to guide the most productive leverage points for intervention to tackle structural stigma and promote effective PLHIV leadership.
Impact of the COVID‐19 pandemic on HIV prevention and care services among key populations across 15 cities in India: a longitudinal assessment of clinic‐based data
Authors: McFall Allison M. , Menezes Neia Prata , Srikrishnan Aylur K. , Solomon Sunil S. , Anand Santhanam , Baishya Jiban J. , Lucas Gregory M. , Celentano David D. , Mehta Shruti H.
Published: July 2022

Introduction

The COVID‐19 pandemic has threatened to diminish gains in HIV epidemic control and impacts are likely most profound among key populations in resource‐limited settings. We aimed to understand the pandemic's impact on HIV‐related service utilization among men who have sex with men (MSM) and people who inject drugs (PWID) across India.

Methods

Beginning in 2013, we established integrated care centres (ICCs) which provide HIV preventive and treatment services to MSM and PWID across 15 Indian sites. We examined utilization patterns for an 18‐month period covering 2 months preceding the pandemic (January–February 2020) and over the first and second COVID‐19 waves in India (March 2020–June 2021). We assessed: (1) unique clients accessing any ICC service, (2) ICC services provided, (3) unique clients tested for HIV and (4) HIV diagnoses and test positivity. Among an established cohort of PWID/MSM living with HIV (PLHIV), we administered a survey on the pandemic's impact on HIV care and treatment (June–August 2020).

Results

Overall, 13,854 unique clients visited an ICC from January 2020 to June 2021. In January/February 2020, the average monthly number of clients was 3761. Compared to pre‐pandemic levels, the number of clients receiving services declined sharply in March 2020, dropping to 25% of pre‐pandemic levels in April/May 2020 (first wave), followed by a slow rebound until April/May 2021 (second wave), when there was a 57% decline. HIV testing followed a similar trajectory. HIV test positivity changed over time, declining in the first wave and reaching its nadir around July 2020 at ∼50% of pre‐pandemic levels. Positivity then increased steadily, eventually becoming higher than pre‐pandemic periods. The second wave was associated with a decline in positivity for MSM but was relatively unchanged for PWID. Among 1650 PLHIV surveyed, 52% of PWID and 45% of MSM reported the pandemic impacted their ability to see an HIV provider. MSM had barriers accessing sexually transmitted infection testing and partner HIV testing.

Conclusions

The COVID‐19 pandemic led to significant decreases in HIV‐related service utilization among key populations in India. This presents an opportunity for increased transmission and patients presenting with advanced disease among groups already disproportionately impacted by HIV.
Fractionation and characterization of sialyl linkage isomers of serum N‐glycans by CE–MS
Authors: Zhou Xiaomei , Song Woran , Novotny Milos V. , Jacobson Stephen C.
Published: July 2022

Structural isomers of sialylated N‐glycans contribute to the diversity of the N‐glycome and to a range of biological functions. Sialyl linkage isomers can be readily distinguished by mass spectrometry with mass differences between α2,3‐ and α2,6‐linkages generated by a two‐step sialic acid linkage‐specific alkylamidation. To improve the identification of N‐glycans from complex mixtures, we added a delactonization step after the first alkylamidation step, which regenerates negatively charged carboxylic acids on α2,3‐sialic acids. N‐glycan isomers with α2,3‐sialic acids are then fractionated by ion‐exchange chromatography prior to the second alkylamidation step. With this modified alkylamidation method, sialylated N‐glycans were enriched and stabilized for structural characterization by capillary electrophoresis–mass spectrometry and tandem mass spectrometry. We identified 52 sialylated N‐glycan structures, including 107 linkage isomers, in human serum and confirmed the presence of positional isomers of specific sialyl linkage isomers. Due to the reduced sample complexity after ion‐exchange fractionation and CE separation, substructural features of N‐glycans were rapidly evaluated and included core‐ and antenna‐fucosylation and poly‐lactosamine.
Hybrid fractional laser treatment for photodamaged facial skin rejuvenation 6 years following fractional CO2: Comparison of clinical outcome and patients' satisfaction
Authors: Fusano Marta , Bencini Pier Luca , Galimberti Michela Gianna
Published: July 2022

Objectives

Fractional carbon dioxide (CO2) laser resurfacing is considered an effective treatment for skin rejuvenation. The request for clinical effectiveness with shorter downtime has led to the development of new hybrid technologies, including a traditional Er:YAG (erbium‐doped yttrium aluminium garnet) fractional laser 2940 nm combined with a simultaneous nonablative 1470 nm wavelength. The aim of this study is to compare clinical outcomes and patients' satisfaction with face resurfacing performed with both the CO2 laser and the hybrid laser.

Methods

Nineteen women underwent ultrapulsed CO2 fractional resurfacing for photodamaged facial skin; the same patients underwent the hybrid laser after almost 6 years. Clinical outcomes and patients' satisfaction were evaluated 6 months after the treatment and compared between the two technologies.

Results

After both CO2 and hybrid treatment a significant improvement was found in terms of fine lines (p < 0.001 and p = 0.004, respectively), tactile roughness (p < 0.001 and p = 0.002, respectively), and mottled pigmentation (both p < 0.001). Healing times and complications were greater with the CO2 laser. Comparing the two technologies, patients showed better results with the CO2 laser for each score's item, but greater satisfaction with the hybrid laser (p = 0.012).

Conclusions

The present study confirms CO2 laser as the most effective treatment; however, the new hybrid technology revealed good results associated with faster healing and less discomfort.
ULP Charges Can Come From Unanticipated Sources
Authors: Wich Scott
Published: July 2022

In NLRB v. FDRLST Media LLC, the U.S. Court of Appeals for the Third Circuit ruled in favor of the employer with respect to a controversial tweet but against the employer on the issue of whether an individual with no relation to the parties has standing to file a complaint with the National Labor Relations Board (NLRB). Both rulings may impact other employers.
Development of a mathematical formula and online tool to calculate the potential maximum flap width to allow for primary anterolateral thigh donor‐site closure in Caucasians
Authors: Thomas Benjamin , Cordts Tomke , Lange Willy , Falkner Florian , Haug Valentin , Aman Martin , Böcker Arne , Vollbach Felix , Gazyakan Emre , Harhaus Leila , Kneser Ulrich , Bigdeli Amir K.
Published: July 2022

Background

Primary anterolateral thigh (ALT) flap donor‐site closure is crucial to achieve patient satisfaction, avoid burdensome secondary surgeries, and avert poor outcomes. Only vague maximum flap width recommendations have been suggested, which fall short of acknowledging individual patient habitus and thigh morphology. Therefore, we aimed at identifying a user‐friendly preoperative calculation of maximum flap width for primary closure.

Methods

A total of 429 ALT free flaps performed between 2009 and 2020 were analyzed. A total of 350 donor‐sites were closed primarily (82%) and 79 (18%) were split‐thickness skin‐grafted (STSG). Patient demographics including sex, age, and BMI, operative details, and flap characteristics were compared to assess their impact on the outcome variable. Receiver operating characteristic (ROC) curves were plotted for all significant predictors discriminating between closure and STSG. Areas under the curve (AUCs) were calculated for each parameter combination and optimal cutoffs were determined using Youden's Index.

Results

Sex, age, BMI, and flap width alone were poor discriminators. Dividing flap width by BMI and logarithmized BMI yielded AUCs of 0.91 and 0.94, respectively. Including patient sex yielded the best fitting regression model (χ2 = 251.939, p < .0001) increasing the AUC to 0.96 (95% CI: 0.93–0.98, p < .0001). The optimal cutoff value discriminated between primary closure and STSG with 90% sensitivity and 89% specificity. An online calculator of patient‐individual maximum ALT width was then programmed.

Conclusions

Sex and BMI are reliable predictors of successful primary ALT donor‐site closure in Caucasians. We devised a novel formula for calculating patient‐individual maximum ALT widths preoperatively, predicting failure of primary closure with 90% sensitivity in our cohort, available at: https://kitteltaschenbuch.com/altwidth/calculate.htm
A questionnaire for physical findings of malnutrition when physical exams are not possible
Authors: Chizmar Lora , Lewis Sherri
Published: July 2022

Background

When nutrition assessments must be performed virtually, such as during the coronavirus pandemic, it is difficult to fully assess patients for malnutrition without the ability to perform a nutrition‐focused physical exam. Practitioners may ask patients about their physical appearance, but there is currently no validated set of questions whose answers correlate with nutrition‐focused physical findings for the diagnosis of malnutrition in such situations. The aim of this study was to evaluate correlations between patients' responses to verbalized questions and physical signs of malnutrition.

Methods

Questions related to the physical findings of malnutrition were developed and evaluated for content validity. Thirty patients receiving nutrition assessments at an acute care veterans' hospital were asked the questions prior to a nutrition‐focused physical exam. Patients' responses were compared with a diagnosis of malnutrition and physical findings of muscle, fat, fluid accumulation, and handgrip strength.

Results

Four questions significantly correlated with malnutrition: “Does the area around your eyes appear sunken in?” (P = 0.03), “Are you able to see your ribs?” (P = 0.05), “Do you feel you are unusually skinny for you?” (P = 0.001), and “Do you find yourself eating less due to swelling in your belly?” (P = 0.008).

Conclusion

There are relationships between patients' responses to certain verbalized questions and their physical status. Such questions can be used to identify physical signs of malnutrition when nutrition‐focused physical exams cannot be performed. Further research is needed to validate these questions in other populations.
A novel method for extracting circulating cell‐free DNA from whole blood samples and its utility in the non‐invasive prenatal test
Authors: Zhong Hongbin , Zeng Liuhong , Tao Mengyuan , Ye Yuchen , Wang Yanqi , Hou Lei , Wu Miaofeng , Liu Hui , Zhang Hongyun , Tang Meifang
Published: July 2022

Objective

We verified a magnetic bead‐based, simple, and fast method for circulating cell‐free DNA (cfDNA) extraction from whole blood samples(CEWB) and characterised its utility in non‐invasive prenatal testing (NIPT).

Method

We extracted cfDNA from both plasma and whole blood of the patients using CEWB and compared it to that extracted using a Qiagen extraction kit; droplet digital polymerase chain reaction test was used to calculate the fragment size bias. In all, 304 samples were used for NIPT.

Results

The CEWB group (mean ± standard deviation [SD]: 4.34 ± 0.41 ng/ml plasma) reported less DNA weight yield than the Qiagen group (4.90 ± 0.50 ng/ml plasma). There was no significant difference between the CEWB group and the Qiagen group in the gene fragments (136 bp: p = 0.064 and 420 bp: p = 0.534). In a parallel cohort study to characterise the utility of the CEWB method in NIPT, the treatment group extracted by CEWB showed a sensitivity of 100%, a specificity of 99.65%, and a positive predictive value of 95%.

Conclusions

This study demonstrated that CEWB achieves an acceptable yield of DNA without contamination from genomic DNA. Subsequent clinical experiments in a parallel cohort indicated its utility for NIPT.
Preparation and Characterization of PANI Surface Modified HMX/F2602 Microcapsule Composites
Authors: Li Yuexin , Xu Wenzheng , Guo Fengwei , Yan Tianlun , Zheng Xin , Wei Yamei , Tan Xianpeng , Wang Jingyu
Published: July 2022

Using HMX with a particle size of 1–10 μm as the main explosive, a dense polyaniline (PANI) shell was prepared on the surface of HMX/F2602 by in situ polymerization, and an energetic composite material HMX−F@PANI (HMX−F2602@PANI) with a microcapsule structure was constructed. The structure and properties of the samples were characterized by SEM, XRD, XPS, DSC, mechanical sensitivity and electrostatic spark sensitivity tests. The results showed that the chemical structure and polycrystalline morphology of the crystals did not change during the coating process, and remained β‐HMX. The preparation of PANI shell greatly improves the coating degree of the explosive surface and reduces the exposure of crystal. In addition, compared with HMX/F2602, HMX−F@PANI is more excellent in improving thermal stability and reducing the electrostatic spark sensitivity, which is attributed to the advantages of microcapsule structure and good electrical conductivity of PANI.
Study‐design in pandemics: From surveillance and performance‐evaluation to licensing and pharmacovigilance
Authors: Bird Sheila M.
Published: July 2022

Andy Grieve, the first pharmaceutical statistician to be President of the Royal Statistical Society, practiced in the regulated world of drug development. With reduction in drug development costs as his motivation, Grieve advanced Bayesian methods for developing predictive methods for efficacy and toxicity ‐ to be used as early as possible in the drug development process; and his presidential address exhorted statisticians to weigh‐in wherever data are used to make decisions. Diagnostic tests for infectious diseases are less regulated than drugs and vaccines unless the blood supply is at risk. Unlike in the HIV and HCV pandemics of the late 20th century, even well‐designed surveys linked to a volunteered biological sample (to be tested for SARS‐CoV‐2 antigen or antibodies) have had modest or low consent rates. Record‐linkage, statistical design and reporting standards have seen triumph and tragedy. Among the triumphs are: Liverpool's insistence on dual testing (lateral flow device; polymerase chain reaction [PCR]) of some 6000 asymptomatic citizens who attended for SARS‐CoV‐2‐screening; two tricky randomized controlled public‐policy trials on daily contact testing for close contacts of index cases of SARS‐CoV‐2 infection versus self‐isolation (with or without initial PCR); and among already‐consented participants in surveillance, over 80% secondary consent for linkage to their health records, including the Immunization Management Service. Before the next pandemic we need to entrench better regulation of diagnostic tests, better informed consent (not via weblinks), better feedback to participants, and transparency about basic safety data.
The Acute Stroke Therapy by Inhibition of Neutrophils study – Key features and impact
Authors: Kirby Simon , Chuang‐Stein Christy
Published: July 2022

The Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) study, initiated in November of the year 2000, is now widely recognized as having been a landmark study in the history of clinical trials. We look at why this is the case by considering its key features and impact. These key features are: the use of Bayesian design and analysis; the use of the normal dynamic linear model; the response adaptive nature of the study; the use of real‐time dosing decisions; and the use of an integrated model to predict 90‐day response on the Scandinavian Stroke Scale. Our overall conclusion is that the ASTIN study's main impact came from showing the clinical trial community the feasibility of the novel design and analysis used when most of these key features were rarely used in industry trials, let alone used together in one trial in a disease area with a tremendous unmet medical need.
Informed decision‐making: Statistical methodology for surrogacy evaluation and its role in licensing and reimbursement assessments
Authors: Weir Christopher J. , Taylor Rod S.
Published: July 2022

The desire, by patients and society, for faster access to therapies has driven a long tradition of the use of surrogate endpoints in the evaluation of pharmaceuticals and, more recently, biologics and other innovative medical technologies. The consequent need for statistical validation of potential surrogate outcome measures is a prime example on the theme of statistical support for decision‐making in health technology assessment (HTA). Following the pioneering methodology based on hypothesis testing that Prentice presented in 1989, a host of further methods, both frequentist and Bayesian, have been developed to enable the value of a putative surrogate outcome to be determined. This rich methodological seam has generated practical methods for surrogate evaluation, the most recent of which are based on the principles of information theory and bring together ideas from the causal effects and causal association paradigms. Following our synopsis of statistical methods, we then consider how regulatory authorities (on licensing) and payer and HTA agencies (on reimbursement) use clinical trial evidence based on surrogate outcomes. We review existing HTA surrogate outcome evaluative frameworks. We conclude with recommendations for further steps: (1) prioritisation by regulators and payers of the application of formal surrogate outcome evaluative frameworks, (2) application of formal Bayesian decision‐analytic methods to support reimbursement decisions, and (3) greater utilization of conditional surrogate‐based licensing and reimbursement approvals, with subsequent reassessment of treatments in confirmatory trials based on final patient‐relevant outcomes.
Simulation of analysis error contributions arising from uncertainties in the parametrisation of deep convection
Authors: Hubans Antoine , Berre Loïk , Bouteloup Yves , Loo Cécile
Published: July 2022

In order to simulate analysis error contributions resulting from observation errors and model errors, a possible methodology is to run a data assimilation ensemble that includes observation perturbations and a multiphysics approach. This method is examined here formally and experimentally, in order to investigate the effects of deep convection parametrisation uncertainties on analysis errors. A linearised expansion of initial condition errors is first employed to decompose them into contributions arising from observation errors and model errors. This is compared formally with a similar expansion for analysis differences resulting from the use of two different model versions, as in a multiphysics approach. Experimental results with the Action de Recherche Petite Echelle Grande Echelle global model are then examined. Observation error contributions are simulated by analysis differences between an unperturbed experiment and another experiment that includes observation perturbations that are drawn from specified observation error covariances. This is compared with analysis differences resulting from the use of two different parametrisation schemes of deep convection. The results indicate that the contribution of convection uncertainties is relatively large in the Tropics, with similar amplitudes to the contribution of observation errors. Simulated model errors are also found to be pronounced in the boundary layer and in convective areas where the analysis constraint by observations is relatively small, due to lower observation density.
Understanding spatiotemporal variability of drought in recent decades and its drivers over identified homogeneous regions of India
Authors: Saharwardi Md Saquib , Kumar Pankaj , Dubey Aditya Kumar , Kumari Amita
Published: July 2022

Drought is a recurring hydroclimatic extreme whose frequency and intensity have increased over India in recent decades, with a detrimental effect on regional water resources. This study addresses the spatiotemporal variability of drought and its plausible mechanism over India from 1951 to 2018. Firstly, six drought‐homogeneous regions are adequately ascertained by applying rotated empirical orthogonal function analysis using the Standardized Precipitation Evapotranspiration Index that captures most of the reported drought and regional hydroclimatic patterns. For the study period, a drying trend is witnessed across the regions though not significant, whereas in recent decades, northeast India (NEI) and some parts of the Indo‐Gangetic plain (IGP) exhibit higher drought frequency. This anomalous drying is attributed to a weakening of the monsoon circulation and accelerated warming caused by changes in the land‐use pattern. The interplay between El Niño Southern Oscillation and the Indian Ocean Dipole largely affects drought's interannual variability, which shows a modified response in recent decades. However, the long‐term decadal drought pattern is found to be strongly teleconnected with a newly discovered Southern Atlantic Oscillation (SAO) index, which reveals a statistically quite significant relationship (>50%) with drought variability. The positive phase of the SAO index is generally associated with drought across the regions except for IGP and NEI. Despite the recent overall wetting trend, drought frequency has enhanced over most of the regions, modulating the regional hydrological cycle.
Performance of an environmentally‐aligned, low maintenance flood alleviation scheme on the Burn of Mosset, Forres, Scotland
Authors: Johnson Matthew F. , Edwards Patrick , Todd Rachael , Castro Janine M. , Thorne Colin R.
Published: July 2022

Flooding of the town of Forres, Scotland prompted the implementation of a flood alleviation scheme (FAS) featuring a low earth‐fill dam constructed upstream of the town to create a flood retention area, limiting peak discharges entering the urban area. Flow through the dam is controlled by a weir, and it was recognised that if coarse sediment, large wood, and/or debris collected at the weir this could adversely affect its performance. To ensure reliable operation of the weir, the “Burn Management Works” (BMW) were designed to reconnect the embanked, elevated river channel to its floodplain, naturally retaining coarse sediment, large wood, and debris upstream of the dam. The FAS became operational on August 28, 2009 and impounded floodwater for the first time just 1 week later. Here, we report the results of monitoring of the BMW performed between 2011 and 2018. We find that the BMW have fulfilled their primary, flood alleviation functions by retaining large amounts of sediment and large wood without the need for maintenance. In so doing, the BMW has evolved from the single‐thread, trapezoidal, pilot channel constructed through the initially dry pasture, to the shifting mosaic of anastomosed channels, ponds, wetlands, and scrublands that now comprise the fully‐connected floodplain. In parallel, local interest groups have transformed this flood defence asset into a bird and wildlife area that is enjoyed by the community. Lessons learned from the BMW can inform other projects seeking to use nature‐based solutions to deliver sustainable flood risk management while simultaneously achieving goals for river restoration and community engagement.
Post‐quantum cryptography techniques for secure communication in resource‐constrained Internet of Things devices: A comprehensive survey
Authors: Kumari Swati , Singh Maninder , Singh Raman , Tewari Hitesh
Published: July 2022

As the number and characteristics of smart devices change, the concept of the Internet of Things (IoT) emerges. The IoT provides the connected devices with a variety of resources that enable effective communication. At this point, several security issues arise to get the sensitive information behind every communication in the IoT. To provide users with security and privacy, cryptographic schemes are adopted, the most popular being public key cryptographic systems (PKC). However, with the advent of quantum computing, the level of security that can be provided by the PKC schemes is a big question. Another important issue is that the IoT environment is resource‐constrained, which necessitates the implementation of lightweight cryptographic algorithms for better security. In response to these issues, the post‐quantum cryptographic (PQC) schemes are one of the significant developments contributing to IoT security in the post‐quantum world. This article examines the key security issues in the IoT environment and examines the effective solutions found in the literature. The problems in IoT in the quantum era are discussed and appropriate solutions by PKC schemes under limited resources in IoT are focused. As the lattice‐based cryptosystems are more effective, the importance of these schemes in the resource‐constrained IoT is highlighted. This survey also leads to feasible future directions that can support developers and researchers in this field.
Automated Windows behavioral tracing for malware analysis
Authors: Rana Shubham , Kumar Nitesh , Handa Anand , Shukla Sandeep K.
Published: July 2022

In malware analysis, there are two problem scenarios—detection and prevention. In prevention, analysts try to quarantine the file before it gets executed in a real system. The file is further analyzed in a sandbox to observe the behavior. Hence, our work shows that our agent captures events for malware analysis. After integration with the sandbox, it produces robust and efficient models. ETW is a Windows in‐build tool with kernel‐level access. We develop an agent using ETW in C++ with proper usage details. We collect data using cuckoo sandbox and ETW agent for 11 546 samples and perform comparative frequency analysis. The performance of various machine learning classifiers is examined on the behavioral data. Random Forest classifier performs the best on the combined (cuckoo+ETW) data with an accuracy of 99.68% and FPR of 0.45%. The improved performance of combined data over cuckoo data on packed and un‐seen malware is also significantly good. In the detection, if malware somehow escapes from the deployed prevention mechanism and gets executed, the analyst tries to detect malicious actions and respond before it is too late. Our agent can tackle such issues and can function as a standalone host‐based monitoring agent to extract kernel‐level information.
Successful management of gastroesophageal intussusception in an adult puma (Puma concolor)
Authors: Koeppel Katja , O'Dell Jacques , Stevenage Craig , van der Zee Hans , Schoeman Johan P.
Published: July 2022

A 7‐year‐old entire female puma (Puma concolor)presented with a history of regurgitation and diarrhoea of 2 weeks duration. Conventional medical management was initially attempted to alleviate the clinical signs, which were unsuccessful. Oesophagoscopy allowed for the diagnosis of gastroesophageal intussusception (GEI) through the observation of gastric mucosa in the lumen of the distal portion of the oesophagus. The intussusception was reduced using the endoscope, which did not result in resolution because the intussusception recurred within 24 hours. A ventral midline celiotomy was performed, followed by a left‐sided belt loop gastropexy. No postoperative complications related to the surgery were observed. The puma resumed eating within 48 hours following the surgery, and no regurgitation recurred for a period of 24 months following surgery. To the knowledge of the authors, this is the first report of GEI in a puma that was successfully resolved.