bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile telephone delivered contingency management for encouraging adherence to supervised methadone consumption: feasibility study for an RCT of clinical and cost-effectiveness (TIES)
Authors: Metrebian N. , Carr E. , Goldsmith K. , Weaver T. , Pilling S. , Shearer J. , Woolston-Thomas K. , Tas B. , Cooper C. , Getty C. A. , van der Waal R. , Kelleher M. , Finch E. , Bijral P. , Taylor D. , Scott J. , Strang J.
Published: January 2021

Background

Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist’s supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients’ attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients’ mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives.

Methods

A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient’s presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures.

Results

Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host.

Conclusion

Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies.

Trial registration

The trial is retrospectively registered, ISRCTN 58958179.
A non-randomised pilot study of the Solutions for Medication Adherence Problems (S-MAP) intervention in community pharmacies to support older adults adhere to multiple medications
Authors: Patton D. E. , Pearce C. J. , Cartwright M. , Smith F. , Cadogan C. A. , Ryan C. , Clark E. , Francis J. J. , Hughes C. M.
Published: January 2021

Background

Older patients prescribed multiple medications commonly experience difficulties with adherence. High-quality evidence on interventions targeting older patients is lacking. Theory is rarely used to tailor adherence solutions. This study aimed to pilot test a novel intervention, developed using the Theoretical Domains Framework, which guides community pharmacists in identifying adherence barriers and delivering tailored solutions (behaviour change techniques). Key study procedures (e.g. recruitment, data collection) for a future randomised controlled trial (cRCT) were also assessed.

Methods

Using purposive sampling, this non-randomised pilot study aimed to recruit 12 community pharmacies (six in Northern Ireland; six in London, England). Pharmacists were trained to deliver the intervention to non-adherent older patients (maximum 10 per pharmacy; target n = 60-120) aged ≥ 65 years (reduced to 50 years due to recruitment challenges) and prescribed ≥ 4 regular medicines. The intervention, guided by an iPad web-application, was delivered over 3-4 face-to-face or telephone sessions, tailored to specific barriers to adherence. We assessed the feasibility of collecting adherence data (primary outcome: self-report and dispensing records), health-related quality of life (HRQOL) and unplanned hospitalisations (secondary outcomes) at baseline and 6-months. The final decision on progressing to a cRCT, using pre-defined ‘stop-amend-go’ criteria, is presented.

Results

Fifteen pharmacists from 12 pharmacies were recruited and trained. One pharmacy subsequently dropped out. Sixty patients were recruited (meeting the ‘Amend’ progression criteria), with 56 receiving the intervention. Adherence barriers were identified for 55 patients (98%) and a wide range of behaviour change solutions delivered (median: 5 per patient). Self-report and dispensing adherence data were available for 37 (61.7%) and 44 (73.3%) patients, respectively. HRQOL data were available for 35 (58.3%) patients. GP-reported and self-reported hospitalisations data were available for 47 (78.3%) and 23 (38.3%) patients, respectively. All progression concepts were met (nine ‘Go’ and three ‘Amend’ criteria).

Conclusion

This study demonstrates the feasibility of key study procedures (e.g. pharmacy recruitment) and delivery of a tailored adherence intervention in community pharmacies. However, modifications are required to enhance issues identified with patient recruitment, retention and missing data. A future definitive cRCT will explore the effectiveness of the intervention.

Trial registration

ISRCTN, ISRCTN73831533, Registered 12 January 2018.
Sensitivity and specificity of tuberculosis signs and symptoms screening and adjunct role of social pathology characteristics in predicting bacteriologically confirmed tuberculosis in Myanmar
Authors: Htet Kyaw Ko Ko , Chongsuvivatwong Virasakdi , Aung Si Thu
Published: January 2021

Background

Globally, using tuberculosis signs and symptoms (TB-SS) as a screening tool has become less important due to its low sensitivity and specificity. We analyzed data from the Myanmar National Tuberculosis (TB) prevalence survey in 2010. The various TB screening models were developed to predict TB by using logistic regression analysis, and their performance on TB prediction was compared by the measures of overall performance, calibration and discrimination ability, and sensitivity and specificity to determine whether social pathology characteristics could be used as a TB screening tool.

Results

Among 51,367 participants, 311 (0.6%) had bacteriologically confirmed TB, of which 37.2% were asymptomatic and 2% had a normal chest X-ray. Out of 32 various combinations of signs and symptoms, having any signs and symptoms gave the best sensitivity of 59.8% and specificity of 67.2%, but chest X-ray (CXR) alone gave the highest sensitivity (95.1%) and specificity (86.3%). The next best combination was cough only with a sensitivity of 24.4% and specificity of 85%. Other combinations had poor sensitivity (< 10%). Among various TB screening models, the overall performance R2 was higher in the combined models of social pathology and TB signs and symptoms as well as the social pathology model, compared to TB-SS models (> 10% versus < 3%), although all TB screening models were perfect to predict TB (Brier score = 0). The social pathology model shows a better calibration, more closer to 45° line of calibration plot with Hosmer-Lemeshow test p value = 0.787, than the combined models while it had a better discrimination ability in area under the curve, AUC = 80.4%, compared to TB-SS models with any signs and symptoms, AUC = 63.5% and with any cough, AUC = 57.1% (DeLong p value = 0.0001). Moreover, at the propensity score cutoff value ≥ 0.0053, the combined and social pathology models had sensitivity of ~ 80% and specificity of ~ 70%. The highest population attributable fraction to predict TB by social pathology characteristics was male gender (42.6%), age ≥ 55 years (31.0%), and underweight (30.4%).

Conclusion

Over one-third of bacteriologically confirmed TB was asymptomatic. The conventional TB-SS screening tool using any TB signs and symptoms had a lower sensitivity and specificity compared to CXR and social pathology screening tools. The social pathology characteristics as TB screening tool had good calibration and can improve the discrimination ability to predict TB than TB-SS screenings and should be encouraged.
A novel plant based intra canal medicament: ease of removal and effect on radicular dentine microhardness
Authors: Aly Yousra , Omar Nada , Kataia Engy M. , Khallaf Maram E. , Zaazou Mohamed H.
Published: January 2021

Background

This study aimed to evaluate the remaining amount of intra canal medicament in the root canals and their effect on microhardness of radicular dentine. In this study, ninety straight single-rooted teeth were used. Teeth were decoronated at the cemento-enamel junction to ensure a uniform root length of 14 mm (± 1 mm). Root canals were prepared using ProTaper rotary files till size F5. The teeth were then randomly assigned to 3 treatment groups (n = 30); Group 1: Ca(OH)2 pastes (Metapex), Group 2: Moringa oleifera leaf powder mixed with Moringa oleifera extract liquid and Group 3: Moringa oleifera root powder mixed with Moringa oleifera extract liquid. The access openings of all teeth were sealed with Cavit and all teeth were kept in the incubator at 37 °C and 100% humidity for 1 week. After 1 week, the intra canal medicament paste was removed from all teeth. For examination of the ease of removal of the intracanal medicaments, root canals were sectioned longitudinally into buccal and lingual halves and were examined under stereomicroscope at 25× magnification. The remaining amount of intracanal medicaments was calculated using image analysis software (Image j). For microhardness evaluation, forty-five specimens were longitudinally sectioned in a bucco-lingual direction then the roots were split. The root segments were then horizontally embedded in autopolymerizing acrylic resin leaving their dentin surface exposed. The dentin surface of the mounted specimens was ground flat and smooth and polished to obtain a smooth surface. Microhardness measurement was recorded for each sample at baseline before and after application of the three intracanal medications using Vickers Microhardness Tester at magnification of 100× using a 25 g load for 10 s.

Results

Regarding the evaluation of the ease of removal of the intracanal medicaments after irrigation: apically, the Ca(OH)2 recorded the highest mean value of the residual remnants with a statistically significant difference with both Moringa oleifera leaf and root. The microhardness evaluation results showed that all groups showed increase in the microhardness after application of the intracanal medicament for 1 week with no statistically significant difference between them.

Conclusions

Moringa oleifera could be removed easily from the root canals and showed increase in the microhardness of root canal dentin similar to the commonly used calcium hydroxide.
Comparison of response to LPS-induced sepsis in three DBA/2 stocks derived from different sources
Authors: Park Ji Won , Lee Su Jin , Kim Ji Eun , Kang Mi Ju , Bae Su Ji , Choi Yun Ju , Gong Jeong Eun , Kim Kil Soo , Jung Young-Suk , Cho Joon-Yong , Choi Yeon Shik , Hwang Dae Youn , Song Hyun Keun
Published: January 2021

Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.
A systematic review comparing the results of early vs delayed ligament surgeries in single anterior cruciate ligament and multiligament knee injuries
Authors: Kim Seong Hwan , Han Sang-Jin , Park Yong-Beom , Kim Dong-Hyun , Lee Han-Jun , Pujol Nicolas
Published: January 2021

Purpose

The purpose of this study was to compare clinical outcomes and incidence of concomitant injuries in patients undergoing early vs delayed surgical treatment of single anterior cruciate ligament (ACL) injury and multiligament knee injury (MLKI).

Methods

A literature search using PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health, and Scopus from their inception to April 30, 2020 was conducted. Studies with levels I to IV evidence reporting the incidence of meniscus or cartilage injury according to early vs delayed surgery in single ACL injuries and MLKIs were included. In the meta-analysis, data based on the number of meniscus and cartilage injuries were extracted and pooled. Lysholm and Tegner scores were analyzed using two-sample Z-tests to calculate the non-weighted mean difference (NMD). A meta-regression analysis was also performed to determine the effect of single ACL injury and MLKI/study design.

Results

Sixteen studies on single ACL injury and 14 studies on MLKI were included in this analysis. In the analysis, there were significant decreases in Lysholm score (NMD − 5.3 [95% confidence interval (CI) − 7.37 to − 3.23]) and Tegner score (NMD − 0.25 [95% CI − 0.45 to − 0.05]) and increases in risk of meniscus tear (odds ratio [OR] 1.73 [95% CI 1.1–2.73], p = 0.01) and cartilage injury (OR 2.48 [95% CI 1.46–4.2], p = 0.0007) in the delayed surgery group regardless of single ACL injury or MLKI. The result of the meta-regression analysis indicated that single ACL injury and MLKI/study design were not significant moderators of overall heterogeneity (p > 0.05).

Conclusions

Our study suggests that delayed ACL surgery significantly resulted in a higher risk of meniscus tear and cartilage injury and decreased Lysholm and Tegner scores compared to early ACL surgery. The Lysholm scores in the delayed MLKI surgery group were significantly decreased, but the risks of meniscus tear and cartilage injury in the delayed MLKI surgery group remained unclear.

Level of evidence

Level III, meta-analysis.
Preparation and characterizations of glyceryl oleate ufasomes of terbinafine hydrochloride: a novel approach to trigger Candida albicans fungal infection
Authors: Bhattacharya Sankha
Published: January 2021

Background

Worldwide fungal infection cases are increasing by leaps and bounds. The patients who are immunocompromised, i.e., cancer and AIDS, are more susceptible to different types of fungal infections like cutaneous candidiasis and its associate infections. The available treatment for such a disease is creams, gels, etc. However, due to the lack of penetrability and higher systematic absorption, these formulations have reported many side effects. To overcome such challenges, various novel drug delivery systems were introduced. The present research focused on the preparation of glyceryl oleate ufasomes of terbinafine hydrochloride using the film hydration method.

Result

The prepared formulations were characterized for globular size (nm), zeta potential (mV), PDI, morphological characteristics, thermal behavior, in vitro drug release, in vitro antifungal activity, and in vitro skin permeation retention studies. After suitable formulation optimization using thin-film hydration method, 3:7 drug to glyceryl oleate ratio, UF3 formulation was found to produce higher drug entrapment efficacy (52.45 ± 0.56%), stable anionic zeta potential (− 33.37 ± 0.231 mV), desired globular size (376.5 ± 0.42 nm), and decent polydispersity index (0.348 ± 0.0345). Diffusion-controlled and zero-order sustained release profile was observed in the optimized UF3 batch. From the 5 days in vitro antifungal activity studies, it confirmed that UF3 ufasomes possessed good applicability in more prolonged therapy.

Conclusion

From the current investigation, it can be concluded that glyceryl oleate ufasomes of terbinafine hydrochloride could be an excellent approach to treat topical fungal infections.
Multidirectional eigenvalue-based coherence attribute for discontinuity detection
Authors: Yan Binpeng , Fang Ruirui , Huang Xingguo , Ou Weiming
Published: January 2021

The conventional coherence attribute is typically applied to migrated full-stack seismic data volumes to detect geologic discontinuities. Recently, multispectral, multiazimuth, and multioffset coherence attributes have been proposed and implemented with different seismic data volumes of specific frequencies, azimuths, and offsets to enhance discontinuities. Generally, geologic anomalies, such as faults and channels, will be better illuminated by a perpendicular rather than a parallel direction for computation. Therefore, we have developed a multidirectional eigenvalue-based coherence attribute by establishing multiple covariance matrices along certain different directions on a single poststack volume. We adopt two methods to compute a multidirectional coherence attribute. One is to compute multiple coherence volumes in different directions and to define the minimum as the final multidirectional coherence. This method is time-consuming, but it could provide partial and overall discontinuity simultaneously. The other method obtains one coherence volume by summing covariance matrices in different directions, which is computationally efficient, but only provides overall discontinuity. The performance of our 3D physical model and field data volumes demonstrates that multidirectional coherence can highlight subtle geologic structures with a higher resolution than conventional coherence. This suggests that a multidirectional coherence attribute may serve as an effective tool for detecting the distribution of geologic discontinuities in seismic interpretation.
Impact of coexisting clay minerals and organic matter on pore growth in the Lower Jurassic Da’anzhai lacustrine shale reservoir in the Northeast Sichuan Basin, West China
Authors: Wang Pengwei , Liu Zhongbao , Chen Xiao , Feng Dongjun , Wang Ruyue , Peng Zeyang
Published: January 2021

Understanding pore growth is of great significance to investigating reservoir performance in shale-gas systems. However, different from the marine shale reservoir, the lacustrine shale reservoir is commonly rich in clay minerals, resulting in a complicated and poorly understood pore system. We have investigated the impact of coexisting clay mineral and organic matter on pore growth in the Lower Jurassic Da’anzhai Shale in the Northeast Sichuan Basin, West China, through performing total organic carbon (TOC) analysis, X-ray diffraction, field-emission scanning electron microscopy, focused ion beam-scanning electron microscopy (FIB-SEM), [Formula: see text] and [Formula: see text] adsorption experiment, and high-pressure mercury intrusion porosimetry. Our results indicate that the Da’anzhai Shale is dominated by clay-mineral-hosted pores, which are commonly filled or partly filled by pyrobitumen. Controlled by organic maceral, organic pores are poorly and heterogeneously developed in pyrobitumen, and minor or even no organic pores grow in vitrinite. Mesopore and macropore are popular in the Da’anzhai Shale reservoir with complex shapes, e.g., slit- or plate-like shapes combined with “ink-bottle” shapes, confirming a pore system dominated by clay-mineral-hosted pores. The weak positive correlation between the clay mineral content and the meso/macropore volume confirms that the clay mineral is a positive contributor to the storage space, and the weak negative correlation between the TOC and the mesopore volume suggests that infilling of pyrobitumen decreases the pore volume significantly. Similar correlations occur between specific surface area and clay mineral/TOC. FIB-SEM observation confirms that the pore system, e.g., the pore size, pore shape, and pore volume, is controlled by the coexisting clay mineral and pyrobitumen filling in a later stage. The calculated plane porosity of the initial inorganic pore and the unfilled inorganic pore in the Da’anzhai Shale is in the range of 3.66%–10.95% and 0.79%–1.46%, respectively, suggesting that 76.66% of inorganic pores is inactive due to pyrobitumen filling. All of this evidence suggests that pore growth in the Da’anzhai Shale is positively contributed by clay minerals, but it is negatively contributed by pyrobitumen filling. Further discussion suggests that pyrobitumen infilling between clay minerals in the Da’anzhai lacustrine shale can decrease the original pore volume significantly, which work together to govern the pore system in shale reservoirs.
Analysing Joker: an attempt to establish diagnosis for a film icon
Authors: Skryabin Valentin Yurievich
Published: January 2021

Todd Phillips's film Joker, a 2019 psychological thriller, has stirred up strong reactions to the portrayal of the lead character's mental disorder, which is never specified. I used DSM-5 criteria to study whether Joker/Arthur Fleck showed signs of a real mental disorder. The psychopathology Arthur exhibits is unclear, preventing diagnosis of psychotic disorder or schizophrenia; the unusual combination of symptoms suggests a complex mix of features of certain personality traits, namely psychopathy and narcissism (he meets DSM-5 criteria for narcissistic personality disorder). He also shows the symptoms of pseudobulbar affect due to traumatic brain injury. This apparent co-occurrence of both mental disorder and a neurological condition may be confusing for audiences trying to understand mental illness.
LEIS ESTADUAIS COMPLEMENTARES À LEI DE INOVAÇÃO FEDERAL: IMPACTO SOBRE A IMPLEMENTAÇÃO DE INOVAÇÃO NAS INDÚSTRIAS DOS ESTADOS BRASILEIROS
Authors: Braga Clara S. C. , Lázaro Jose Carlos
Published: January 2021

Este estudo tem como objetivo investigar se a adoção de leis de inovação complementares pelos estados impactou a implementação de inovações por parte da indústria local. A pesquisa é descritiva, com a utilização de dados da Pesquisa de Inovação – IBGE (PINTEC), nos triênios de 2000, 2003, 2005, 2008 e 2011. Para a comparação do desempenho inovativo entre estados, é utilizada a técnica de ANOVA para medidas repetidas. Os resultados demonstraram que 12 dos 14 estados apresentaram redução no número de empresas que implementaram inovação entre 2008 e 2011. Evidenciou-se, ainda, que não há diferençasignificativa na implementação de inovações por parte da indústria local nos estados que possuem leis complementares de inovação e aqueles que ainda não as implementaram.
Prehabilitation during a pandemic: preoperative exercise to improve fitness in patients undergoing complex surgery for cancer of the lung or oesophagus, the PRE-HIIT trial: an updated study protocol
Authors: Sheill Grainne , Guinan Emer , O'Neill Linda , Smyth Emily , Normand Charles , L. Doyle Suzanne , Moore Sarah , Newell John , McDermott Grainne , Ryan Ronan , V. Reynolds John , Hussey Juliette
Published: January 2021

Background: Pre-operative fitness is an established predictor of postoperative outcome; accordingly, targeting pre-operative fitness through exercise prehabilitation has logical appeal. Exercise prehabilitation for patients with cancer of the lung or oesophagus is challenging to implement due to the short opportunity for intervention between diagnosis and surgery. In addition, there are now additional challenges to providing prehabilitation during the coronavirus disease 2019 (COVID-19) pandemic due to concerns about social distancing and minimising patient contact. The PRE-HIIT project will examine the influence of virtually delivered exercise prehabilitation on physiological outcomes and postoperative recovery.

Methods: The PRE-HIIT randomised controlled trial (RCT) will compare a 2-week high intensity interval training programme to standard preoperative care in a cohort of patients with thoracic and oesophageal cancers. A protocol for this study has been published previously. As a result of the COVID-19 pandemic, changes to the study assessment battery and the mode of intervention delivery have been made. The PRE-HIIT programme will now be a home-based intervention. Both the exercise intervention and standard care will be delivered via telehealth. The recruitment target for the study remains 78 participants. There is no change to the primary outcome of the study; cardiorespiratory fitness. Secondary outcomes include measures of pulmonary and physical function, quality of life and post-operative morbidity. Outcomes will be measured at baseline and post-intervention. The impact of PRE-HIIT on well-being will be examined qualitatively with interviews post-intervention (T1). This revised protocol will also explore participant’s satisfaction with delivery of prehabilitation via telehealth. The healthcare costs associated with the PRE-HITT programme will also be examined.

Discussion: The overall aim of this RCT is to examine the effect of tailored, individually prescribed high intensity interval training on pre-operative fitness and postoperative recovery for patients undergoing complex surgical resections.

Trial registration: ClinicalTrials.Gov NCT03978325 07/06/2019
Price-Directed Cost Sharing and Demand Allocation Among Service Providers with Multiple Demand Sources and Multiple Facilities
Authors: Liu Hanlin , Yu Yimin , Benjaafar Saif , Wang Huihui
Published: January 2021

Problem definition: We consider capacity sharing through demand allocation among firms with multiple demand sources and multiple service facilities. Firms decide on the allocation of demand from different sources to different facilities to minimize delay costs and service-fulfillment costs possibly subject to service-level requirements. If firms decide to operate collectively as a coalition, they must also decide on a scheme for sharing the total cost. Academic/practical relevance: We study capacity sharing through demand allocation in service systems in the presence of service-fulfillment costs. Our problem is motivated by service collaboration in healthcare involving public–private partnerships. Methodology: We formulate the problem as a cooperative game and identify a cost allocation that is in the core. Results: The cost-allocation scheme we identify is price-directed, and the cost of each firm consists of three components: (1) the delay cost incurred within the firm; (2) a cost paid for the capacity used by the firm at facilities owned by other firms; and (3) a payment received for fulfilling demand of other firms at facilities owned by the firm. Interestingly, we show that the cost-allocation scheme is equivalent to a market equilibrium—that is, it can be implemented in a decentralized fashion. We extend our analysis to settings where the capacity of each facility is endogenously determined and to settings where a service-priority policy is deployed. Our results are robust to a variety of generalizations: partial sharing, partial transfer, facilities modeled as general queueing systems, and convex delay costs. Managerial implications: Our findings provide guidelines for and insights into how to carry out demand allocation and cost sharing among different firms in the presence of service-fulfillment costs to foster service collaboration. In particular, the equilibrium market prices can be viewed as the prices/subsidies for service collaboration in a public–private partnership.
Effect of Loci-Kit Models on Students’ Academic Performance in Technical Drawing in Edo State Technical Colleges, Nigeria
Authors: Oviawe Jane Itohan , Uddin Patrick S.O.
Published: January 2021

The study investigated the effect of loci-kit models on students’ academic performance in technical drawing in Edo State technical colleges using non-equivalent control group quasi-experimental research design. Two research questions and two null hypotheses guided the study. The population for this study consisted of 864 vocational II students from the six technical colleges in Edo State. The sample for the study comprised of 110 (60 males and 50 females) randomly selected from all the technical colleges in Edo State. The instrument for data collection was Technical Drawing Achievement Test (TDAT). Three experts validated the instrument. The reliability of the instrument was determined using Kuder Richardson 21 (KR-21) formulae and a reliability coefficient of .85 was obtained. The research questions were answered using Mean and standard deviation while Analysis of Covariance (ANCOVA) was used to test the hypotheses at .05 level of significance. Findings from the study revealed that Loci-kit model was effective in enhancing technical college students’ performance in technical drawing topic loci; there was no significant mean effect of gender on students’ Mean performance score in Technical Drawing. In line with the findings of the study, it was recommended among others that Technical Drawing teachers should employ innovative approaches such as loci-kit models during instructions of loci concepts in technical drawing to facilitate students’ academic performance in the subject.
On-Chip Hybrid Plasmonics Goes Modular
Authors: Tuniz Alessandro , Palomba Stefano , Martijn de Sterke C.
Published: January 2021

Plasmonic devices enable extreme photonic miniaturization and extreme light–matter interactions, but their integration with conventional photonic circuits has proved challenging. In work that was published this year, we offered an approach for hybrid silicon–plasmonic devices that enables modular design of the plasmonic elements.
Deep Learning to Refocus 3D Images
Authors: Wu Yichen , Rivenson Yair , Wang Hongda , Luo Yilin , Ben-David Eyal , Bentolila Laurent A. , Pritz Christian , Ozcan Aydogan
Published: January 2021

High-throughput volumetric fluorescence microscopic imaging remains an important challenge in biology, life sciences and engineering. Imaging 3D fluorescent samples usually involves scanning to acquire images at different focal planes, reducing imaging speed and increasing potential photodamage to the sample. As an alternative approach, we have created a deep-learning-based framework, Deep-Z, to digitally refocus 2D fluorescence microscopic images onto user-defined 3D surfaces.
Lassa viral dynamics in non-human primates treated with favipiravir or ribavirin
Authors: Lingas Guillaume , Rosenke Kyle , Safronetz David , Guedj Jérémie
Published: January 2021

Lassa fever is an haemorrhagic fever caused by Lassa virus (LASV). There is no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, the nucleotide analogue favipiravir showed a high antiviral efficacy, with 100% survival obtained in an otherwise fully lethal non-human primate (NHP) model of Lassa fever. However the mechanism of action of the drug is not known and the absence of pharmacokinetic data limits the translation of these results to the human setting. Here we aimed to better understand the antiviral effect of favipiravir by developping the first mathematical model recapitulating Lassa viral dynamics and treatment. We analyzed the viral dynamics in 24 NHPs left untreated or treated with ribavirin or favipiravir, and we put the results in perspective with those obtained with the same drugs in the context of Ebola infection. Our model estimates favipiravir EC50 in vivo to 2.89 μg.mL-1, which is much lower than what was found against Ebola virus. The main mechanism of action of favipiravir was to decrease virus infectivity, with an efficacy of 91% at the highest dose. Based on our knowledge acquired on the drug pharmacokinetics in humans, our model predicts that favipiravir doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus and provide a milestone towards a future use in humans.
Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway
Authors: Ricciardi Alessandra , Bennuru Sasisekhar , Tariq Sameha , Kaur Sukhbir , Wu Weiwei , Elkahloun Abdel G. , Arakelyan Anush , Shaik Jahangheer , Dorward David W. , Nutman Thomas B. , Tolouei Semnani Roshanak
Published: January 2021

We have previously shown that the microfilarial (mf) stage of Brugia malayi can inhibit the mammalian target of rapamycin (mTOR; a conserved serine/threonine kinase critical for immune regulation and cellular growth) in human dendritic cells (DC) and we have proposed that this mTOR inhibition is associated with the DC dysfunction seen in filarial infections. Extracellular vesicles (EVs) contain many proteins and nucleic acids including microRNAs (miRNAs) that might affect a variety of intracellular pathways. Thus, EVs secreted from mf may elucidate the mechanism by which the parasite is able to modulate the host immune response during infection. EVs, purified from mf of Brugia malayi and confirmed by size through nanoparticle tracking analysis, were assessed by miRNA microarrays (accession number GSE157226) and shown to be enriched (>2-fold, p-value<0.05, FDR = 0.05) for miR100, miR71, miR34, and miR7. The microarray analysis compared mf-derived EVs and mf supernatant. After confirming their presence in EVs using qPCR for these miRNA targets, web-based target predictions (using MIRPathv3, TarBAse and MicroT-CD) predicted that miR100 targeted mTOR and its downstream regulatory protein 4E-BP1. Our previous data with live parasites demonstrated that mf downregulate the phosphorylation of mTOR and its downstream effectors. Additionally, our proteomic analysis of the mf-derived EVs revealed the presence of proteins commonly found in these vesicles (data are available via ProteomeXchange with identifier PXD021844). We confirmed internalization of mf-derived EVs by human DCs and monocytes using confocal microscopy and flow cytometry, and further demonstrated through flow cytometry, that mf-derived EVs downregulate the phosphorylation of mTOR in human monocytes (THP-1 cells) to the same degree that rapamycin (a known mTOR inhibitor) does. Our data collectively suggest that mf release EVs that interact with host cells, such as DC, to modulate host responses.
Predicting the spatio-temporal spread of West Nile virus in Europe
Authors: García-Carrasco José-María , Muñoz Antonio-Román , Olivero Jesús , Segura Marina , Real Raimundo
Published: January 2021

West Nile virus is a widely spread arthropod-born virus, which has mosquitoes as vectors and birds as reservoirs. Humans, as dead-end hosts of the virus, may suffer West Nile Fever (WNF), which sometimes leads to death. In Europe, the first large-scale epidemic of WNF occurred in 1996 in Romania. Since then, human cases have increased in the continent, where the highest number of cases occurred in 2018. Using the location of WNF cases in 2017 and favorability models, we developed two risk models, one environmental and the other spatio-environmental, and tested their capacity to predict in 2018: 1) the location of WNF; 2) the intensity of the outbreaks (i.e. the number of confirmed human cases); and 3) the imminence of the cases (i.e. the Julian week in which the first case occurred). We found that climatic variables (the maximum temperature of the warmest month and the annual temperature range), human-related variables (rain-fed agriculture, the density of poultry and horses), and topo-hydrographic variables (the presence of rivers and altitude) were the best environmental predictors of WNF outbreaks in Europe. The spatio-environmental model was the most useful in predicting the location of WNF outbreaks, which suggests that a spatial structure, probably related to bird migration routes, has a role in the geographical pattern of WNF in Europe. Both the intensity of cases and their imminence were best predicted using the environmental model, suggesting that these features of the disease are linked to the environmental characteristics of the areas. We highlight the relevance of river basins in the propagation dynamics of the disease, as outbreaks started in the lower parts of the river basins, from where WNF spread towards the upper parts. Therefore, river basins should be considered as operational geographic units for the public health management of the disease.
Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers
Authors: Ruzhanskaya Anna , Ichihara Kiyoshi , Evgina Svetlana , Skibo Irina , Vybornova Nina , Vasiliev Anton , Agarkova Galina , Emanuel Vladimir
Published: January 2021

Objectives

A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 22 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population.

Methods

According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 758 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 17 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age.

Results

SDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5% males and 11.3% females); for insulin, those with BMI≥28 kg/m2 (31%); for the thyroid panel, those with anti-thyroid antibodies (10.3% males; 24.5% females), for CEA those with smoking habit (30% males and 16% females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for alpha-fetoprotein, CEA, all sex-hormones for females, FSH and progesterone for both sexes. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol for females in postmenopause, and progesterone for females in premenopause, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit.

Conclusion

RIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.
A study of evaluating specific tissue oxygen saturation values of gastrointestinal tumors by removing adherent substances in oxygen saturation imaging
Authors: Nishihara Keiichiro , Hori Keisuke , Saito Takaaki , Omori Toshihiko , Sunakawa Hironori , Minamide Tatsunori , Suyama Masayuki , Yamamoto Yoichi , Yoda Yusuke , Shinmura Kensuke , Ikematsu Hiroaki , Yano Tomonori
Published: January 2021

Objectives

Oxygen saturation (OS) imaging is a new method of endoscopic imaging that has clinical applications in oncology which can directly measure tissue oxygen saturation (Sto2) of the surface of gastrointestinal tract without any additional drugs or devices. This imaging technology is expected to contribute to research into cancer biology which leads to clinical benefit such as prediction to efficacy of chemotherapy or radiotherapy. However, adherent substances on tumors such as blood and white coating, pose a challenge for accurate measurements of the StO2 values in tumors. The aim of this study was to develop algorithms for discriminating between the tumors and their adherent substances, and to investigate whether it is possible to evaluate the tumor specific StO2 values excluding adherent substances during OS imaging.

Methods

We plotted areas of tumors and their adherent substances using white-light images of 50 upper digestive tumors: blood (68 plots); reddish tumor (83 plots); white coating (89 plots); and whitish tumor (79 plots). Scatter diagrams and discriminating algorithms using spectrum signal intensity values were constructed and verified using validation datasets. StO2 values were compared between the tumors and tumor adherent substances using OS images of gastrointestinal tumors.

Results

The discriminating algorithms and their accuracy rates (AR) were as follows: blood vs. reddish tumor: Y> - 4.90X+7.13 (AR: 95.9%) and white coating vs. whitish tumor: Y< -0.52X+0.17 (AR: 96.0%). The StO2 values (median, [range]) were as follows: blood, 79.3% [37.8%–100.0%]; reddish tumor, 74.5% [62.0%–86.9%]; white coating, 73.8% [42.1%–100.0%]; and whitish tumor, 65.7% [53.0%–76.3%].

Conclusions

OS imaging is strongly influenced by adherent substances for evaluating the specific StO2 value of tumors; therefore, it is important to eliminate the information of adherent substances for clinical application of OS imaging.
Predicting field-goal success according to offensive, defensive and contextual variables in elite men’s wheelchair basketball
Authors: Francis John W. , Owen Alun J. , Peters Derek M.
Published: January 2021

The purposes of this study were to (i) develop a field-goal shooting performance analysis template and (ii) explore the impact of each identified variable upon the likely outcome of a field-goal attempt using binary logistic regression modelling in elite men’s wheelchair basketball. First, a field-goal shooting performance analysis template was developed that included 71 Action Variables (AV) grouped within 22 Categorical Predictor Variables (CPV) representing offensive, defensive and game context variables. Second, footage of all 5,105 field-goal attempts from 12 teams during the men’s 2016 Rio De Janeiro Paralympic Games wheelchair basketball competition were analysed using the template. Pearson’s chi-square analyses found that 18 of the CPV were significantly associated with field-goal attempt outcome (p < 0.05), with seven of them reaching moderate association (Cramer’s V: 0.1–0.3). Third, using 70% of the dataset (3,574 field-goal attempts), binary logistic regression analyses identified that five offensive variables (classification category of the player, the action leading up to the field-goal attempt, the time left on the clock, the location of the shot, and the movement of the player), two defensive variables (the pressure being exerted by the defence, and the number of defenders within a 1-meter radius) and 1 context variable (the finishing position of the team in the competition) affected the probability of a successful field-goal attempt. The quality of the developed model was determined acceptable (greater than 65%), producing an area under the curve value of 68.5% when the model was run against the remaining 30% of the dataset (1,531 field-goal attempts). The development of the model from such a large sample of objective data is unique. As such it offers robust empirical evidence to enable coaches, performance analysts and players to move beyond anecdote, in order to appreciate the potential effect of various and varying offensive, defensive and contextual variables on field-goal success.
What could prevent chronic condition admissions assessed as preventable in rural and metropolitan contexts? An analysis of clinicians’ perspectives from the DaPPHne study
Authors: Longman Jo , Johnston Jennifer , Ewald Dan , Gilliland Adrian , Burke Michael , Mutonga Tabeth , Passey Megan
Published: January 2021

Introduction

Reducing potentially preventable hospitalisations (PPH) is a priority for health services. This paper describes the factors that clinicians perceived contributed to preventable admissions for angina, diabetes, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD), and what they considered might have been done in the three months leading up to an admission to prevent it.

Methods

The study was conducted in a rural and a metropolitan health district in NSW, Australia. Expert Panels reviewed detailed case reports to assess preventability. For those admissions identified as preventable, comments from clinicians indicating what they perceived could have made a difference and/or been done differently to prevent each of the preventable admissions were analysed qualitatively.

Results

148 (46%) of 323 admissions were assessed as preventable. Across the two districts, the most commonly identified groups of contributing factors to preventable admissions were: ‘Systems issues: Community based services missing or inadequate or not referred to’; ‘Patient issues: Problems with adherence/self-management’; and ‘Clinician issues: GP care inadequate’. In some instances, important differences drove these groups of factors. For example, in the rural district ‘Systems issues: Community based services missing or inadequate or not referred to’ was largely driven by social and welfare support services missing/inadequate/not referred to, whereas in the metropolitan district it was largely driven by community nursing, allied health, care coordination or integrated care services missing/inadequate/not referred to. Analyses revealed the complexity of system, clinician and patient factors contributing to each admission. Admissions for COPD (rural) and CHF (metropolitan) admissions showed greatest complexity.

Discussion and conclusion

These findings suggest preventability of individual admissions is complex and context specific. There is no single, simple solution likely to reduce PPH. Rather, an approach addressing multiple factors is required. This need for comprehensiveness may explain why many programs seeking to reduce PPH have been unsuccessful.