bluuebunny/crossref_metadata_2025 huggingface dataset:
Governing industrial estates on Jakarta's periurban area: From shadow government to network governance
Authors: Hudalah Delik
Published: February 2017

This article investigates the way in which periurban politics have mediated foreign direct investment relocations and facilitated the spatial restructuring of the Jakarta Metropolitan Area (JMA), one of the largest and fastest‐growing megaurban regions in Asia. We conducted a series of in‐depth interviews in Cikarang, the largest, most developed industrial estate corridor in the urban periphery of JMA. We identified institutional settings, power struggles and governance mechanisms underlying the industrial estate transitions in the past three decades. We found that periurban governance in JMA has resulted in poor infrastructure connectivity and tight interactor and inter‐regional competition. As global economic turbulence and decentralization policies restrict the effectiveness of privatization strategies, network strategies are trialled to promote sustainability and inclusiveness in JMA's industrial estates and towns.
Gender Relations, Livelihood Strategies, Water Policies and Structural Adjustment in the Australian Dairy Industry
Authors: Alston Margaret , Clarke Josephine , Whittenbury Kerri
Published: February 2017

Concerns about water scarcity and consequent environmental impacts are driving major structural adjustment in the Australian irrigated dairy industry. This has resulted in government policy initiatives including water licence buybacks and grant schemes to improve water use efficiency. One consequence is the loss of many small farms and the development of larger technologically efficient farms with altered access to irrigation water. In farm families, who dominate the dairy industry, livelihood strategies, labour demands and the boundaries between traditional female and male spheres of labour are changing. We present findings from an Australian Research Council funded project examining the impacts of these changes on dairy families in the Murray Dairy region. We note that reshaped livelihood strategies and increased labour demands are further entrenching traditional gender relations and that labour is being re‐allocated in highly gendered ways. We note a ‘farmer‐manager’ role is evolving amongst male dairy farmers and a critical but less public role comprising significant input to labour tasks is evident amongst women on larger farms. Drawing on interviews with couples, most of whom were interviewed separately, we examine how gendered livelihood strategies are being reshaped at the same time as the significant contributions of women are being obscured.
Seasonal changes of lower respiratory tract infections in lung transplant recipients during the first post‐transplant year: The Hungarian experience
Authors: Kovats Zsuzsanna , Bohacs Aniko , Sutto Zoltan , Vincze Krisztina , Lukacsovits Jozsef , Losonczy Gyorgy , Müller Veronika
Published: February 2017

Background

After lung transplantation (LuTX) a high level of immunosuppression is needed to prevent rejection of the graft. Together with earlier colonization by pathogens, immunosuppression makes recipients more susceptible to infections, especially during the first postoperative year. As seasonality of lower respiratory tract infections (LRTI) is well‐known in chronic lung diseases, we assessed seasonal changes of pathogen spectrum and number of infections in the first postoperative year in LuTX recipients.

Methods

LRTI were analyzed in 28 Hungarian adult LuTX patients. Incidence and spectrum of microorganism causing LRTI were evaluated according to post‐transplant time and seasonal temperature and humidity changes.

Results

A total of 69 cases of LRTI were registered (average: 1.9 cases/patient; range: 0‐14). Gram‐negative=59, gram‐positive=26, and fungal=31 pathogens were detected, with polymicrobial samples in 46% of all cases. Increased number of LRTI was observed in the cold season (1.68±1.54 vs 0.79±0.92 case/month/patient, P<.01) and significant negative correlations were identified between the incidence of polymicrobial and bacterial infections and temperature (r2=0.1535, P<.05, r2=0.3144, P<.01, respectively). In addition, positive correlation was observed between polymicrobial infections and humidity (r2=0.1403, P<.05). Higher incidence of LRTI was also noted in the cold season, when accounting for the differences in immunosuppression.

Conclusion

Seasons influenced the incidence of LRTI in the first postoperative year in LuTX recipients. More intensive vigilance for possible gram‐negative and polymicrobial infections is needed in these patients in cold and wet seasons in the continental climate zone, regardless of underlying disease.
How to quantify microparticles in RBCs? A validated flow cytometry method allows the detection of an increase in microparticles during storage
Authors: Gamonet Clémentine , Mourey Guillaume , Aupet Sophie , Biichle Sabéha , Petitjean Régis , Vidal Chrystelle , Pugin Aurore , Naegelen Christian , Tiberghien Pierre , Morel Pascal , Angelot‐Delettre Fanny , Seilles Estelle , Saas Philippe , Bardiaux Laurent , Garnache‐Ottou Francine
Published: February 2017

BACKGROUND

The procoagulant and proinflammatory microparticles (MPs) released during storage of packed red blood cells (pRBCs) can potentially modify transfusion benefits. A robust method to quantify MPs in pRBCs is needed to evaluate their impact in clinical trials.

STUDY DESIGN AND METHODS

The objective was to validate the preanalytic conditions required to prepare pRBC supernatant as well as a method to quantify and evaluate MP variations over 42 days of pRBC storage.A flow cytometry method with size‐calibrated beads was developed and fully validated. Quantification of MPs in pRBCs (n = 109) was assessed during short‐term (7 days) and long‐term (42 days) storage at 4°C, during short‐term storage (8 hours) at room temperature, and after 2 years frozen.

RESULTS

Repeatability, reproducibility, and linearity of the quantification method were validated, and variations during conservation are presented. There was high variability in RBC (erythrocyte) MP (ERMP) and platelet MP (PMP) levels between RBC units, depending on the filter used for leukocyte reduction. During the 42 days of storage at 4°C, significant increases in ERMPs and PMPs occurred (from 58 to 138 ERMPs/µL from Day 2 to Day 42; p = 0.0002; and from 326 to 771 PMPs/µL from Day 2 to Day 42; p = 0.00026).

CONCLUSION

We use a robust method to confirm that ERMPs and PMPs are present to various degrees in pRBCs and that storage for 42 days significantly increases their generation. This method is robust enough to allow MP quantification in pRBCs and is adapted to evaluate the clinical impact of transfused MPs in prospective clinical trials.
Process mining is an underutilized clinical research tool in transfusion medicine
Authors: Quinn Jason G. , Conrad David M. , Cheng Calvino K.
Published: February 2017

BACKGROUND

To understand inventory performance, transfusion services commonly use key performance indicators (KPIs) as summary descriptors of inventory efficiency that are graphed, trended, and used to benchmark institutions.

STUDY DESIGN AND METHODS

Here, we summarize current limitations in KPI‐based evaluation of blood bank inventory efficiency and propose process mining as an ideal methodology for application to inventory management research to improve inventory flows and performance.

RESULTS

The transit of a blood product from inventory receipt to final disposition is complex and relates to many internal and external influences, and KPIs may be inadequate to fully understand the complexity of the blood supply chain and how units interact with its processes. Process mining lends itself well to analysis of blood bank inventories, and modern laboratory information systems can track nearly all of the complex processes that occur in the blood bank.

CONCLUSION

Process mining is an analytical tool already used in other industries and can be applied to blood bank inventory management and research through laboratory information systems data using commercial applications. Although the current understanding of real blood bank inventories is value‐centric through KPIs, it potentially can be understood from a process‐centric lens using process mining.
The characteristics of hepatitis B surface antigen (HBsAg)‐negative hepatitis B virus (HBV) infection in Chinese blood donors: a follow‐up study of donors tested negative for HBsAg and reactive for simultaneous nucleic acid testing of HBV, hepatitis C virus, and human immunodeficiency virus
Authors: Guo Zhaofu , Fu Ping , Yin Yijin , Wang Funeng , Yin Yiqing , Wang Jingxing , Liu Yu
Published: February 2017

BACKGROUND

The real infection status of hepatitis B virus (HBV) of hepatitis B surface antigen (HBsAg)‐negative yet nucleic acid test (NAT)‐positive blood donors is difficult to clarify. Detailed follow‐up study is needed for analyzing the infectivity of these blood donors.

STUDY DESIGN AND METHODS

Blood donors who screened negative for HBsAg and reactive for simultaneous NAT of HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) were included in a follow‐up epidemiologic questionnaire survey and contributed follow‐up samples for further testing. The follow‐up samples were tested repeatedly for the serologic markers and HBV DNA. The genotypes and sequence mutations of HBV infected by 11 HBV DNA–positive donors were analyzed through the amplification and sequencing of HBV S region.

RESULTS

Of the 46 donors included in this study, 89.1% were infected with HBV (41/46), including one (2.2%) window period infection, three (6.5%) recovered infections, and 37 (80.4%) occult HBV infections (OBIs). The S region of HBV was successfully amplified and sequenced for seven donors, five infected with Genotype B (71.4%), one with Genotype C (14.3%), and one with Genotype D (14.3%). Mutations in the S region were detected in four donors (57.1%)

CONCLUSIONS

This is the first detailed study with multiple follow‐up testing of the HBV infection status among blood donors who were tested negative for HBsAg and reactive for simultaneous NAT of HBV, HCV, and HIV. Most of these donors were infected with HBV with very low viral load. Our findings indicate that it is important to improve the sensitivity of NAT so as to decrease the residual risk of transfusion‐transmitted HBV infection.
A probable case of West Nile virus transfusion transmission
Authors: Groves Jamel A. , Shafi Hedyeh , Nomura Jim H. , Herron Ross M. , Baez Devin , Dodd Roger Y. , Stramer Susan L.
Published: February 2017

BACKGROUND

Transfusion‐transmitted West Nile virus (WNV) infection is infrequent as a result of minipool (MP) and individual‐donation (ID) nucleic acid testing (NAT) of blood donations. ID‐NAT is triggered on the basis of local WNV activity identified by MP‐NAT.

STUDY DESIGN AND METHODS

A 78‐year‐old male patient who was treated for cardiac disease received 14 blood components from 30 donors in August 2016. He was discharged 7 days after aortic valve replacement and coronary bypass surgery, but was re‐admitted on Day 12 with symptoms of viral infection, and eventually was diagnosed with aseptic meningitis. The patent died on Day 51.

RESULTS

The patient was positive for WNV‐immunoglobulin M (IgM) antibodies in his cerebrospinal fluid on Day 14 and was positive for WNV‐IgM (on Days 14 and 16) and WNV‐IgG antibodies (on Day 16) in his serum. All associated donations were nonreactive by MP‐NAT or ID‐NAT. However, one MP‐NAT was noted to have an elevated (but negative) signal‐to‐cutoff ratio, and one donor from that MP was subsequently found positive for WNV‐IgM and IgG antibodies; the donor was diagnosed with a WNV‐like viral syndrome that had an onset 3 to 5 days postdonation. The donor's plasma was transfused 12 days before the patient's onset of WNV‐meningoencephalitis. Conversion to ID‐NAT was triggered for the region 7 days after the implicated donation, which was associated with the region's first human WNV case.

CONCLUSION

Despite the possibility of mosquito‐borne transmission, this was considered to be a case of transfusion‐transmitted WNV infection from an MP‐NAT–nonreactive donation collected just before triggering conversion to ID‐NAT; a rare event recognized once in 84 million donations.
Educational interventions encouraging appropriate use of blood transfusions
Authors: Abelow A. , Gafter‐Gvili A. , Tadmor B. , Lahav M. , Shepshelovich D.
Published: February 2017

Background and Objectives

The integration of a restrictive packed red blood cells (PRBC) transfusion strategy into daily clinical practice presents a challenge. This study describes the effect of an intervention including educational presentations and computerized alerts on PRBC utilization at a tertiary hospital.

Materials and Methods

During December 2014, lectures describing recommended PRBC transfusion indications were presented to all non‐intensive care departments. Starting from January 2015, an alert was added to the electronic drug ordering system recommending transfusions at a haemoglobin (Hb) level <7 g/dl or Hb < 8 g/dl in symptomatic patients. The physician was not required to acknowledge the alert. Data regarding measured Hb preceding transfusions were collected. The primary end‐point was defined as the percentage of PRBC administered at Hb ≥ 8 g/dl in 2015 compared with 2014. Secondary end‐points were the percentage of PRBC administered to patients with Hb < 7 g/dl and the absolute number of PRBC transfused in 2015 compared with 2014.

Results

Compared to 2014, in 2015, the percentage of PRBC transfused when the Hb ≥ 8 g/dl was reduced by 18·8% (P < 0·001) and made up 29% of the total PRBC transfused. The absolute number of PRBC transfused decreased by 7·7%. The percentage of PRBC transfused when the Hb < 7 g/dl increased by 25·9% (P < 0·001).

Conclusions

Following the described intervention, there was a significant improvement in the appropriateness of PRBC transfusions in our medical centre. These changes occurred despite the lack of interruption of the physician's workflow from the computerized alert. This simple strategy might be of use in implementing a restrictive PRBC transfusion strategy.
Driving variables for eutrophication in lakes of Hanoi by data‐driven technique
Authors: Hoang Thu‐Huong Thi , Van Anh Dieu , Nguyen Hien Thi Thu
Published: February 2017

To investigate eutrophication in 31 freshwater lakes in Hanoi, Vietnam, water quality and Chlorophyll‐a content were monitored to calculate trophic indices. Twelve of the 15 urban lakes investigated were eutrophic, of which five were hypertrophic, while only seven of the 16 suburban lakes were eutrophic. The Trophic Index (TRIX) was the best predictive index to identify the eutrophication level of the lakes. Classification trees (CTs) were applied to study the trophic status of lakes and identify the driving variables. The results demonstrated that eutrophication in the lakes of Hanoi was driven by nutrients and organic enrichment, as well as by inappropriate management such as unplanned embankment and water uses. DIN, BOD, lake size and embankment were the key parameters controlling eutrophication in the lakes of Hanoi.
Benefits of a Regional Evidence‐Based Practice Fellowship Program: A Test of the ARCC Model
Authors: Kim Son Chae , Ecoff Laurie , Brown Caroline E. , Gallo Ana‐Maria , Stichler Jaynelle F. , Davidson Judy E.
Published: February 2017

Background

The Advancing Research and Clinical practice through close Collaboration (ARCC) model postulates that improvement in nurses’ evidence‐based practice (EBP) beliefs results in improved EBP implementation, which in turn improves nurse‐related outcomes, such as nurses’ job satisfaction and group cohesion. However, there is a dearth of interventional studies that evaluate the relationships among these variables.

Aims

This study evaluated whether a regional EBP fellowship program improved participants’ EBP beliefs, EBP implementation, job satisfaction, group cohesion, and group attractiveness, and examined the relationships among these improvements, using structural equation modeling.

Methods

A pretest–posttest design was used among three annual cohorts of a regional, 9‐month EBP fellowship program, from 2012 to 2014, in San Diego, California. Matched pretest and posttest questionnaires, including EBP Beliefs, EBP Implementation, Job Satisfaction, Group Cohesion, and Group Attractiveness scales, were analyzed (N = 120).

Results

Paired t‐tests showed statistically significant improvements in EBP beliefs, EBP implementation, job satisfaction, and group cohesion (p < .05). Structural equation modeling showed that improvement in EBP implementation had no direct effect on improvements in job satisfaction, group cohesion, or group attractiveness. However, improvement in EBP beliefs had direct effects on improvements in job satisfaction (β = .24; p = .002) and group attractiveness (β = .22; p = .010).

Linking Evidence to Action

A regional, collaborative EBP fellowship program was effective in improving EBP beliefs, EBP implementation, job satisfaction, and group cohesion. Improvement in EBP beliefs appears to have had direct effects on improvements in job satisfaction and group attractiveness. Regional fellowship programs that educate and support EBP champions and their mentors may enhance EBP adoption in nursing practice across multiple health care institutions.
A Volatility Analysis of Agricultural Commodity and Crude Oil Global Markets
Authors: Trabelsi Jamel , Jelassi Mohamed Mehdi , Lo Gaye Del
Published: February 2017

The purpose of this study is to provide insights on volatility features of major agricultural commodity global markets. In order to achieve this, we estimate the volatility in the global markets of crude oil and four main agricultural commodities, namely rice, wheat, cotton and coffee over the period 1980:2014. We also investigate the nexus between the volatilities in these global markets. More precisely, we first model the volatility of agricultural commodity and crude oil markets based on the GARCH methodology. Second, we assess the risk in these global markets by the Value-at-Risk technique. Finally, we evaluate the co-movements between returns in agricultural commodity and crude oil markets by the copula methodology. Our empirical findings reveal that, unlike in the financial market, upside shocks in the agricultural market tend to increase volatility more than downside shocks do. In addition to that, risk in global agricultural commodity markets turned out to be high and little evidence in favor of interdependence between these markets is found. Moreover, the co-movement between agricultural commodity market risk and oil prices is detected for recent years only and little evidence is found for the whole sample period.
Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol
Authors: Canata Gian , Casale Valentina , Chiey Alfredo
Published: February 2017

Purpose: this study was conducted to identify the most effective method of postoperative pain management, comparing the intravenous opiate infusion protocol with the use of a single periarticular local anesthetic infiltration (LAI) in patients undergoing total knee arthroplasty (TKA) surgery.

Methods: 50 patients submitted to TKA surgery between 2013 and 2015 were divided into two groups. Buprenorphine was administered intravenously to the patients in Group A, while the Group B patients received a single periarticular LAI (ropivacaine and ketorolac) during surgery.

Pain was assessed using a visual analog scale (VAS) and the knee injury and osteoarthritis outcome score. Hemoglobin and hematocrit were measured in the early postoperative period and at 40 days post-surgery. Range of motion and inflammatory markers were also assessed. Statistical analysis was performed using Student’s t-test.

Results: student’s t-test showed no significant difference between the groups in functional outcomes or blood values, but a difference in VAS score on the day of surgery was found (p < 0.0001), in favor of Group B.

Conclusions: LAI considerably reduces postoperative pain, allowing rapid mobilization and accelerating functional recovery.

Level of evidence: Level I, prospective single-blind randomized trial.
Living Rough: Hunter Gatherers of Tiamoana
Authors: Revell Leo , Jaye Chrystal
Published: February 2017

This article is based on a qualitative study of modest scope that set out to gain a sense of the daily life of homeless people in a New Zealand regional city. We present our data in the form of an ‘impressionistic tale’ (van Maanen 2011) to convey a day in the life of a homeless person living rough on the streets. Our findings confirm what is already known; that homeless people occupy the crevices of urban spaces. Their daily work is driven by imperatives of finding food, clothing and shelter as well as alcohol and other substances, and keep- ing out of the way of the public and the police. Despite the hardship, some homeless people enjoy the freedom of being feral. We propose that re-housing homeless people requires addressing structural barriers that compound the harsh realities of homelessness such as anomalies in government and social agencies and the social stigma accrued from criminal records. It also requires overcoming the negative capital accumulated from adverse lifecourses, and improved government support for the social and health services that care for the most marginalised people in society.
Reliable bearing fault diagnosis using Bayesian inference-based multi-class support vector machines
Authors: Islam M. M. Manjurul , Kim Jaeyoung , Khan Sheraz A. , Kim Jong-Myon
Published: February 2017

This letter presents a multi-fault diagnosis scheme for bearings using hybrid features extracted from their acoustic emissions and a Bayesian inference-based one-against-all support vector machine (Bayesian OAASVM) for multi-class classification. The Bayesian OAASVM, which is a standard multi-class extension of the binary support vector machine, results in ambiguously labeled regions in the input space that degrade its classification performance. The proposed Bayesian OAASVM formulates the feature space as an appropriate Gaussian process prior, interprets the decision value of the Bayesian OAASVM as a maximum a posteriori evidence function, and uses Bayesian inference to label unknown samples.
Understanding Zika Virus Stability and Developing a Chimeric Vaccine through Functional Analysis
Authors: Xie Xuping , Yang Yujiao , Muruato Antonio E. , Zou Jing , Shan Chao , Nunes Bruno T. D. , Medeiros Daniele B. A. , Vasconcelos Pedro F. C. , Weaver Scott C. , Rossi Shannan L. , Shi Pei-Yong
Published: February 2017

Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E. X. Y. Lim, S. Zhang, G. Fibriansah, T.-S. Ng, J. S. G. Ooi, J. Shi, and S.-M. Lok, Nature 533:425–428, 2016,
https://doi.org/10.1038/nature17994
). Here we report the functional analysis of the structural information in the context of complete ZIKV and DENV-2 virions. Swapping the prM-E genes between ZIKV and DENV-2 switched the thermostability of the chimeric viruses, identifying the prM-E proteins as the major determinants for virion thermostability. Shortening the extended loop of the E protein by 1 amino acid was lethal for ZIKV assembly/release. Mutations (Q350I and T351V) that abolished the extra hydrogen-bond interaction between the E proteins did not reduce ZIKV thermostability, indicating that the extra interaction does not increase the thermostability. Interestingly, mutant T351V was attenuated in A129 mice defective in type I interferon receptors, even though the virus retained the wild-type thermostability. Furthermore, we found that a chimeric ZIKV with the DENV-2 prM-E and a chimeric DENV-2 with the ZIKV prM-E were highly attenuated in A129 mice; these chimeric viruses were highly immunogenic and protective against DENV-2 and ZIKV challenge, respectively. These results indicate the potential of these chimeric viruses for vaccine development.

IMPORTANCE
Analysis of a recently observed high-resolution structure of ZIKV led to a hypothesis that its unusual stability may contribute to the associated, unique disease outcomes. Here we performed a functional analysis to demonstrate that viral prM-E genes are the main determinants for the high stability of ZIKV. The extra hydrogen-bond interaction (observed in the high-resolution structure) between ZIKV E proteins did not enhance virion stability, whereas the extended loop of E protein (CD loop in domain III) was essential for ZIKV assembly. More importantly, we found that a chimeric ZIKV with DENV-2 prM-E genes and a chimeric DENV-2 with ZIKV prM-E genes were highly attenuated in A129 mice. Mice immunized with these chimeric viruses generated robust neutralizing antibody responses and were fully protected from DENV-2 and ZIKV challenge, respectively, indicating that these chimeric viruses could be further developed as vaccine candidates.
Selective Whole-Genome Amplification Is a Robust Method That Enables Scalable Whole-Genome Sequencing of
Plasmodium vivax
from Unprocessed Clinical Samples
Authors: Cowell Annie N. , Loy Dorothy E. , Sundararaman Sesh A. , Valdivia Hugo , Fisch Kathleen , Lescano Andres G. , Baldeviano G. Christian , Durand Salomon , Gerbasi Vince , Sutherland Colin J. , Nolder Debbie , Vinetz Joseph M. , Hahn Beatrice H. , Winzeler Elizabeth A.
Published: February 2017

Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of
Plasmodium vivax
, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an
ex vivo
culture system. Current techniques used to enrich
P. vivax
DNA from clinical samples require significant resources or are not consistently effective. Here, we demonstrate that selective whole-genome amplification (SWGA) can enrich
P. vivax
gDNA from unprocessed human blood samples and dried blood spots for high-quality WGS, allowing genetic characterization of isolates that would otherwise have been prohibitively expensive or impossible to sequence. We achieved an average genome coverage of 24×, with up to 95% of the
P. vivax
core genome covered by ≥5 reads. The single-nucleotide polymorphism (SNP) characteristics and drug resistance mutations seen were consistent with those of other
P. vivax
sequences from a similar region in Peru, demonstrating that SWGA produces high-quality sequences for downstream analysis. SWGA is a robust tool that will enable efficient, cost-effective WGS of
P. vivax
isolates from clinical samples that can be applied to other neglected microbial pathogens.

IMPORTANCE
Malaria is a disease caused by
Plasmodium
parasites that caused 214 million symptomatic cases and 438,000 deaths in 2015.
Plasmodium vivax
is the most widely distributed species, causing the majority of malaria infections outside sub-Saharan Africa. Whole-genome sequencing (WGS) of
Plasmodium
parasites from clinical samples has revealed important insights into the epidemiology and mechanisms of drug resistance of malaria. However, WGS of
P. vivax
is challenging due to low parasite levels in humans and the lack of a routine system to culture the parasites. Selective whole-genome amplification (SWGA) preferentially amplifies the genomes of pathogens from mixtures of target and host gDNA. Here, we demonstrate that SWGA is a simple, robust method that can be used to enrich
P. vivax
genomic DNA (gDNA) from unprocessed human blood samples and dried blood spots for cost-effective, high-quality WGS.
ATP-Dependent Persister Formation in
Escherichia coli
Authors: Shan Yue , Brown Gandt Autumn , Rowe Sarah E. , Deisinger Julia P. , Conlon Brian P. , Lewis Kim
Published: February 2017

Persisters are dormant variants that form a subpopulation of cells tolerant to antibiotics. Persisters are largely responsible for the recalcitrance of chronic infections to therapy. In
Escherichia coli
, one widely accepted model of persister formation holds that stochastic accumulation of ppGpp causes activation of the Lon protease that degrades antitoxins; active toxins then inhibit translation, resulting in dormant, drug-tolerant persisters. We found that various stresses induce toxin-antitoxin (TA) expression but that induction of TAs does not necessarily increase persisters. The 16S rRNA promoter
rrnB
P1 was proposed to be a persister reporter and an indicator of toxin activation regulated by ppGpp. Using fluorescence-activated cell sorting (FACS), we confirmed the enrichment for persisters in the fraction of
rrnB
P1
-gfp
dim cells; however, this is independent of toxin-antitoxins.
rrnB
P1 is coregulated by ppGpp and ATP. We show that
rrnB
P1 can report persisters in a
relA
/
spoT
deletion background, suggesting that
rrnB
P1 is a persister marker responding to ATP. Consistent with this finding, decreasing the level of ATP by arsenate treatment causes drug tolerance. Lowering ATP slows translation and prevents the formation of DNA double-strand breaks upon ﬂuoroquinolone treatment. We conclude that variation in ATP levels leads to persister formation by decreasing the activity of antibiotic targets.

IMPORTANCE
Persisters are a subpopulation of antibiotic-tolerant cells responsible for the recalcitrance of chronic infections. Our current understanding of persister formation is primarily based on studies of
E. coli
. The activation of toxin-antitoxin systems by ppGpp has become a widely accepted model for persister formation. In this study, we found that stress-induced activation of mRNA interferase-type toxins does not necessarily cause persister formation. We also found that the persister marker
rrnB
P1 reports persister cells because it detects a drop in cellular ATP levels. Consistent with this, lowering the ATP level decreases antibiotic target activity and, thus, leads to persister formation. We conclude that stochastic variation in ATP is the main mechanism of persister formation. A decrease in ATP provides a satisfactory explanation for the drug tolerance of persisters, since bactericidal antibiotics act by corrupting energy-dependent targets.
A Ferredoxin- and F
420
H
2
-Dependent, Electron-Bifurcating, Heterodisulfide Reductase with Homologs in the Domains
Bacteria
and
Archaea
Authors: Yan Zhen , Wang Mingyu , Ferry James G.
Published: February 2017

Heterodisulfide reductases (Hdr) of the HdrABC class are ancient enzymes and a component of the anaerobic core belonging to the prokaryotic common ancestor. The ancient origin is consistent with the widespread occurrence of genes encoding putative HdrABC homologs in metabolically diverse prokaryotes predicting diverse physiological functions; however, only one HdrABC has been characterized and that was from a narrow metabolic group of obligate CO
2
-reducing methanogenic anaerobes (methanogens) from the domain
Archaea
. Here we report the biochemical characterization of an HdrABC homolog (HdrA2B2C2) from the acetate-utilizing methanogen
Methanosarcina acetivorans
with unusual properties structurally and functionally distinct from the only other HdrABC characterized. Homologs of the HdrA2B2C2 archetype are present in phylogenetically and metabolically diverse species from the domains
Bacteria
and
Archaea
. The expression of the individual HdrA2, HdrB2, and HdrB2C2 enzymes in
Escherichia coli
, and reconstitution of an active HdrA2B2C2 complex, revealed an intersubunit electron transport pathway dependent on ferredoxin or coenzyme F
420
(F
420
H
2
) as an electron donor. Remarkably, HdrA2B2C2 couples the previously unknown endergonic oxidation of F
420
H
2
and reduction of ferredoxin with the exergonic oxidation of F
420
H
2
and reduction of the heterodisulfide of coenzyme M and coenzyme B (CoMS-SCoB). The unique electron bifurcation predicts a role for HdrA2B2C2 in Fe(III)-dependent anaerobic methane oxidation (ANME) by
M. acetivorans
and uncultured species from ANME environments. HdrA2B2C2, ubiquitous in acetotrophic methanogens, was shown to participate in electron transfer during acetotrophic growth of
M. acetivorans
and proposed to be essential for growth in the environment when acetate is limiting.

IMPORTANCE
Discovery of the archetype HdrA2B2C2 heterodisulfide reductase with categorically unique properties extends the understanding of this ancient family beyond CO
2
-reducing methanogens to include diverse prokaryotes from the domains
Bacteria
and
Archaea
. The unprecedented coenzyme F
420
-dependent electron bifurcation, an emerging fundamental principle of energy conservation, predicts a role for HdrA2B2C2 in diverse metabolisms, including anaerobic CH
4
-oxidizing pathways. The results document an electron transport role for HdrA2B2C2 in acetate-utilizing methanogens responsible for at least two-thirds of the methane produced in Earth’s biosphere. The previously unavailable heterologous production of individual subunits and the reconstitution of HdrA2B2C2 with activity have provided an understanding of intersubunit electron transfer in the HdrABC class and a platform for investigating the principles of electron bifurcation.
Widespread compression associated with Eocene Tonga-Kermadec subduction initiation
Authors: Sutherland R. , Collot J. , Bache F. , Henrys S. , Barker D. , Browne G.H. , Lawrence M.J.F. , Morgans H.E.G. , Hollis C.J. , Clowes C. , Mortimer N. , Rouillard P. , Gurnis M. , Etienne S. , Stratford W.
Published: February 2017

Eocene onset of subduction in the western Pacific was accompanied by a global reorganization of tectonic plates and a change in Pacific plate motion relative to hotspots during the period 52–43 Ma. We present seismic-reflection and rock sample data from the Tasman Sea that demonstrate that there was a period of widespread Eocene continental and oceanic compressional plate failure after 53–48 Ma that lasted until at least 37–34 Ma. We call this the Tectonic Event of the Cenozoic in the Tasman Area (TECTA). Its compressional nature is different from coeval tensile stresses and back-arc opening after 50 Ma in the Izu-Bonin-Mariana region. Our observations imply that spatial and temporal patterns of stress evolution during western Pacific Eocene subduction initiation were more varied than previously recognized. The evolving Eocene geometry of plates and boundaries played an important role in determining regional differences in stress state.
Climate-driven thaw of permafrost preserved glacial landscapes, northwestern Canada
Authors: Kokelj Steven V. , Lantz Trevor C. , Tunnicliffe Jon , Segal Rebecca , Lacelle Denis
Published: February 2017

Ice-marginal glaciated landscapes demarcate former boundaries of the continental ice sheets. Throughout circumpolar regions, permafrost has preserved relict ground ice and glacigenic sediments, delaying the sequence of postglacial landscape change that transformed temperate environments millennia earlier. Here we show that within 7 × 106 km2 of glaciated permafrost terrain, extensive landscapes remain poised for major climate-driven change. Across northwestern Canada, 60–100-km-wide concentric swaths of thaw slump–affected terrain delineate the maximum and recessional positions of the Laurentide Ice Sheet. These landscapes comprise ∼17% of continuous permafrost terrain in a 1.27 × 106 km2 study area, indicating widespread preservation of late Pleistocene ground ice. These thaw slump, relict ground ice, and glacigenic terrain associations are also evident at the circumpolar scale. Recent intensification of thaw slumping across northwestern Canada has mobilized primary glacial sediments, triggering a cascade of fluvial, lacustrine, and coastal effects. These geologically significant processes, highlighted by the spatial distribution of thaw slumps and patterns of fluvial sediment mobilization, signal the climate-driven renewal of deglaciation and postglacial permafrost landscape evolution.
Alternating Southern and Northern Hemisphere climate response to astronomical forcing during the past 35 m.y.
Authors: De Vleeschouwer David , Vahlenkamp Maximilian , Crucifix Michel , Pälike Heiko
Published: February 2017

Earth’s climate has undergone different intervals of gradual change as well as abrupt shifts between climate states. Here we aim to characterize the corresponding changes in climate response to astronomical forcing in the icehouse portion of the Cenozoic, from the latest Eocene to the present. As a tool, we use a 35-m.y.-long δ18Obenthic record compiled from different high-resolution benthic isotope records spliced together (what we refer to as a megasplice).We analyze the climate response to astronomical forcing during four 800-k.y.-long time windows. During the mid-Miocene Climatic Optimum (ca. 15.5 Ma), global climate variability was mainly dependent on Southern Hemisphere summer insolation, amplified by a dynamic Antarctic ice sheet; 2.5 m.y. later, relatively warm global climate states occurred during maxima in both Southern Hemisphere and Northern Hemisphere summer insolation. At that point, the Antarctic ice sheet grew too big to pulse on the beat of precession, and the Southern Hemisphere lost its overwhelming influence on the global climate state. Likewise, we juxtapose response regimes of the Miocene (ca. 19 Ma) and Oligocene (ca. 25.5 Ma) warming periods. Despite the similarity in δ18Obenthic values and variability, we find different responses to precession forcing. While Miocene warmth occurs during summer insolation maxima in both hemispheres, Oligocene global warmth is consistently triggered when Earth reaches perihelion in the Northern Hemisphere summer. This pattern is in accordance with previously published paleoclimate modeling results, and suggests an amplifying role for Northern Hemisphere sea ice.
Willingness of patients with diabetes to use an ICT-based self-management tool: a cross-sectional study
Authors: Shibuta Tomomi , Waki Kayo , Tomizawa Nobuko , Igarashi Ayumi , Yamamoto-Mitani Noriko , Yamaguchi Satoko , Fujita Hideo , Kimura Shigeko , Fujiu Katsuhito , Waki Hironori , Izumida Yoshihiko , Sasako Takayoshi , Kobayashi Masatoshi , Suzuki Ryo , Yamauchi Toshimasa , Kadowaki Takashi , Ohe Kazuhiko
Published: February 2017

Objectives

To examine the prevalence of the willingness of patients with diabetes to use a self-management tool based on information and communication technology (ICT) such as personal computers, smartphones, and mobile phones; and to examine the patient characteristics associated with that willingness.

Research design and methods

We conducted a cross-sectional interview survey of 312 adults with diabetes at a university hospital in an urban area in Japan. Participants were classified into 2 groups: those who were willing to use an ICT-based self-management tool and those who were unwilling. Multiple logistic regression analysis was used to identify factors associated with the willingness, including clinical and social factors, current use of ICT, self-management practices, self-efficacy, and diabetes-related emotional distress.

Results

The mean age of the 312 participants was 66.3 years (SD=11.5) and 198 (63%) were male. Most of the participants (93%) had type 2 diabetes. Although only 51 (16%) currently used ICT-based self-management tools, a total of 157 (50%) expressed the willingness to use such a tool. Factors associated with the willingness included: not having nephropathy (OR=2.02, 95% CI 1.14 to 3.58); outpatient visits once a month or more (vs less than once a month, OR=2.13, 95% CI 1.13 to 3.99); current use of personal computers and/or smartphones (OR=4.91, 95% CI 2.69 to 8.98); and having greater diabetes-related emotional distress (OR=1.10, 95% CI 1.01 to 1.20).

Conclusions

Approximately half of the patients showed interest in using an ICT-based self-management tool. Willing patients may expect ICT-based self-management tools to complement outpatient visits and to make self-management easier. Starting with patients who display the willingness factors might optimize programs based on such tools.
Systematic review of pathways for the delivery of allergy services
Authors: Diwakar Lavanya , Cummins Carole , Lilford Richard , Roberts Tracy
Published: February 2017

Objectives

The incidence and prevalence of allergies worldwide has been increasing and allergy services globally are unable to keep up with this increase in demand. This systematic review aims to understand the delivery of allergy services worldwide, challenges faced and future directions for service delivery.

Methods

A systematic scoping review of Ovid, EMBASE, HMIC, CINAHL, Cochrane, DARE, NHS EED and INAHTA databases was carried out using predefined inclusion and exclusion criteria. Data on the geographical region, study design and treatment pathways described were collected, and the findings were narratively reported. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Results

205 publications were screened and 27 selected for review. Only 3 were prospective studies, and none included a control group. There were no eligible publications identified from North America, Africa, Australia and most parts of Asia. Most publications relate to allergy services in the UK. In general, allergy services globally appear not to have kept pace with increasing demand. The review suggests that primary care practitioners are not being adequately trained in allergy and that there is a paucity of appropriately trained specialists, especially in paediatric allergy. There appear to be considerable barriers to service improvement, including lack of political will and reluctance to allocate funds from local budgets.

Conclusions

Demand for allergy services appears to have significantly outpaced supply. Primary and secondary care pathways in allergy seem inadequate leading to poor referral practices, delays in patient management and consequently poor outcomes. Improvement of services requires strong public and political engagement. There is a need for well-planned, prospective studies in this area and a few are currently underway. There is no evidence to suggest that any given pathway of service provision is better than another although data from a few long-term, prospective studies look very promising.
Fall-related attendance and associated hospitalisation of children and adolescents in Hong Kong: a 12-year retrospective study
Authors: Lee James Chun-Yin , Tung Keith Tsz-Suen , Li Tim M H , Ho Frederick Ka-Wing , Ip Patrick , Wong Wilfred Hing-Sang , Chow Chun-Bong
Published: February 2017

Objectives

The present study aimed to examine the trends and characteristics of fall-related attendance in accident and emergency department (AED) by injury type and the trend in associated average length of stay (LOS) among children and adolescents in Hong Kong.

Design

A retrospective approach was adopted.

Setting

AED, involving all local public emergency departments from 2001 to 2012.

Participants

63 557 subjects aged 0–19 years with fall injury record were included in the analysis.

Primary outcome measures

Fall-related injury number and rates were calculated and reported. Poisson and negative binomial regression models were used to study the trends of injury incidence rate at different body regions.

Results

AED fall-related attendance rate increased significantly with an annual percentage change of 4.45 (95% CI 3.43 to 5.47%, p<0.0001). The attendance number of male subjects was persistently higher than female subjects. The standardised rate of fracture injury increased by 1.31% (95% CI 0.56 to 2.05%, p<0.0001) and that of non-fracture injury increased by 9.23% (95% CI 7.07 to 11.43%, p<0.0001) annually. Upper limb was the most frequently fractured location. It included forearm/elbow, shoulder/upper arm and wrist/hand with descending order of frequency. On the contrary, head was the most frequent non-fracture location, followed by forearm/elbow.

Conclusions

The rates of fall-related attendance have been increasing and still remain high. There were significant increases in non-fracture injuries. Fractures were most frequently found in the upper extremity of a child while the most common non-fracture location was head. It appears that more efforts should be made and preventive measures should be implemented for children and adolescents in Hong Kong.
Improving malodour management in advanced cancer: a 10-year retrospective study of topical, oral and maintenance metronidazole
Authors: George Reena , Prasoona Thotampuri Shanthi , Kandasamy Ramu , Cherian Renitha , Celine Thangarathi , Jeba Jenifer , Murali Shakila , Mathew David
Published: February 2017

Objectives

To explore the relative effectiveness of topical or oral metronidazole used for malodour in necrotic cancers and to propose a protocol for metronidazole usage in managing malodour.

Methods

A retrospective case note review of the management of malodour over 10 years comparing outcomes with topical, intermittent and maintenance oral metronidazole.

Results

Among 179 patients treated for malodour, the commonest primaries were cervical (45%), and head and neck cancers (40%). Outcomes were poor during the period when only topical or intermittent oral metronidazole was used. Topical use gradually decreased (97% vs 55%) and the proportion of patients receiving maintenance oral metronidazole increased (0% in 2003–2004 vs 93% in 2011). Concurrently, there was reduction in documented malodour (12.5% of visits per patient in 2003–2004 vs 1.5% in 2011, p<0.01).

Conclusions

Our data support formulary guidelines recommending maintenance metronidazole for recurrent malodour. Dimethyl trisulfide, a product of anaerobic necrosis causes malodour and can attract maggot-producing flies to decaying tissues. Therefore, to reduce anaerobic malodour in vulnerable settings, we propose a ladder for metronidazole titration. High-risk patients should start with 400 mg thrice daily ×7 days and continue 200 mg once daily. The SNIFFF severity (Smell-Nil, Faint, Foul or Forbidding) can guide follow-up dosage: 200 mg once daily to continue for nil or faint smell; breakthrough courses of 400 mg thrice daily ×1 week for foul smell and 2 weeks for forbidding smell, followed by 200 mg once daily.

The effectiveness and limitations of maintenance metronidazole and the SNIFFF ladder should be prospectively evaluated.
Target geotechnical reliability for redundant foundation systems
Authors: Naghibi Farzaneh , Fenton Gordon A.
Published: February 2017

Geotechnical support systems (e.g., deep and shallow foundations) generally involve at least some redundancy. For example, if a building is supported by np separate foundations, then failure (e.g., excessive settlement) of a single foundation will generally not result in failure of the building if the building is able to shed the load from the failed foundation to adjacent foundations. This load-shedding ability lends the foundation system redundancy — system failure only occurs if multiple foundations fail. This paper investigates the relationship between the level of geotechnical redundancy, individual foundation reliability, and system reliability for deep foundations (piles). In the particular case where the pile resistance remains constant after achieving its ultimate capacity (at a certain displacement), the relationship between individual and system reliabilities is computed theoretically. The more general case, where the load carried by the pile reduces after exceeding its ultimate capacity, is investigated by Monte Carlo simulation. Charts relating system and individual reliability indices are presented, which can be used to aid in the design of individual piles as part of a pile support system.