bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacologic, Pharmacodynamic, and Pharmacokinetic Considerations with Intravenous Ibuprofen Lysine
Authors: Capparelli Edmund V.
Published: October 2020

Patent ductus arteriosus (PDA) is a common complication in preterm infants. An intravenous (IV) cyclooxygenase (COX) inhibitor is the pharmacotherapy of choice. Concerns over adverse effects associated with the traditional treatment, IV indomethacin, have led to the investigation of other COX inhibitors to assist closure of PDA. IV ibuprofen lysine is a COX inhibitor that demonstrates similar efficacy to indomethacin with few adverse effects. In addition, IV ibuprofen lysine does not cause reductions in cerebral, renal, and mesenteric blood flow that can be seen with indomethacin, and thus ibuprofen therapy is not associated with reduced renal function. Ibuprofen is primarily metabolized by cytochrome P450 (CYP) 2C9. The immaturity of neonatal biotransformation pathways has a pronounced effect on the pharmacokinetic parameters of ibuprofen, particularly because CYP2C9 enzyme activity is known to be very low at birth and to increase rapidly over the first several days of life. Ibuprofen is highly bound to albumin, raising concern that ibuprofen may displace bilirubin and subsequently increase free bilirubin concentrations. However, the ibuprofen concentrations achieved with approved dosing with IV ibuprofen lysine are lower than those expected to result in displacement of bilirubin and related adverse effects. Factors such as gestational age and CYP2C9 polymorphism may affect ibuprofen metabolism and therefore optimal dosing, but further clinical investigation is needed in these areas. Other areas for future investigation include prolonged dosing regimens, prophylactic administration, and alternate indications. At the approved dose, IV ibuprofen lysine is a safe, effective pharmacologic agent to promote closure of PDAs in preterm infants.
Once Daily Dosing of Aminoglycosides in Pediatric Cystic Fibrosis Patients: A Review of the Literature
Authors: Wassil Sarah K. , Fox Kristie M. , White James W.
Published: October 2020

Patients with cystic fibrosis receive many courses of antibiotic therapy throughout their lifetime. Dosing aminoglycosides once daily has become common practice in many of these individuals. Due to ease of home administration, decreased nursing time, and improved quality of life, this regimen is being increasingly explored in the cystic fibrosis population. Because patients with cystic fibrosis have increased aminoglycoside clearance, once daily dosing may result in a prolonged time during the dosing interval when concentrations of the drug may be undetectable. This makes the use of once daily dosing of these antibiotics in patients with cystic fibrosis controversial. Although aminoglycosides exhibit a post antibiotic effect, the duration of this effect is unknown in humans; therefore, the development of resistance to the aminoglycoside is a concern. This manuscript will review the organisms most commonly associated with a pulmonary exacerbation of cystic fibrosis, the properties of the aminoglycoside that make once daily dosing feasible, the concept of once daily dosing in those with cystic fibrosis and the current literature regarding efficacy, monitoring, toxicity and concerns of resistance with once daily dosing in this population.
A Retrospective Study Evaluating the Effectiveness of an Asthma Clinical Pathway in Pediatric Inpatient Practice
Authors: Edwards Elisa , Fox Kristie
Published: October 2020

OBJECTIVE To determine if the asthma clinical pathway implemented at Wolfson Children's Hospital reduces the length of hospital stay. To determine if pathway use affected the use of asthma education, the use of appropriate discharge medications based on asthma classification, and readmission rates.

METHODS A list of patients aged 2 to 18 years discharged from Wolfson Children's Hospital between September 1, 2004 and August 31, 2006 with the diagnosis of asthma was generated. Medical records of eligible patients were reviewed for demographic information, asthma pathway use, duration of hospital stay in days, readmission rates, receipt of asthma education, and medications prescribed upon discharge. Patients placed on the asthma clinical pathway were compared to a control group with asthma who were matched based on age and discharge date. Length of stay was averaged for each group. Asthma education, discharge medications, and readmission rates were compared between the two groups.

RESULTS Forty-three patients placed on the asthma clinical pathway were compared to a 43 patients in the control group that were matched for age and discharge date. Use of the asthma clinical pathway reduced hospital stay by 0.372 days (P = .0373). Receipt of asthma education (P = .3864), the use of appropriate drug therapy prescribed upon discharge (P = .1398), and readmission rates (P = .5486) were unaffected by pathway use.

CONCLUSIONS The asthma clinical pathway used at Wolfson Children's Hospital reduces length of hospital stay, but has no bearing on receipt of asthma education, use of appropriate drug therapy upon discharge, or readmission rates.
Griseofulvin Only Modestly Diminishes Persistence of Trichophyton tonsurans on the Scalp of Carriers
Authors: Abdel-Rahman Susan M. , Wright Krista J. , Navarre Harriett C.
Published: October 2020

OBJECTIVES Using genetic strain typing, we previously identified a high rate of T. tonsurans carriage among preschool-aged children attending an urban daycare center. No treatment was provided as part of the observational study; however, children when symptomatic were treated in accordance with daycare policies. This retrospective investigation examines antifungal drug therapy received during the previous investigation and characterizes the impact of treatment on persistence of the fungus on the scalp.

METHODS Children in whom serial typeable isolates of T. tonsurans were recovered were eligible for evaluation. Clinic charts were reviewed and dispensing records obtained from the primary pharmacies serving the daycare. Infection patterns were examined before and after treatment.

RESULTS We identified 72 dispensing records for 53 children, all of whom received griseofulvin. Nine children could not be evaluated because treatment was coincident with their last study visit. Thus, 63 treatment events in 44 children with 331 discrete infection events remained. After a single course of griseofulvin, 22.7% of children became culture negative, 6.8% acquired another strain of T. tonsurans and, 70.5% remained persistently positive with the same strain carried prior to treatment. Among those receiving a second course of therapy, 54% remained positive and the cumulative percent of children that became culture negative increased to 36.4%. If children subsequently acquiring a different strain are considered together with those that became culture negative, cumulative strain clearance was observed in 43% of children. Neither the griseofulvin dose nor the duration of time over which children were infected prior to treatment differed between those that remained positive and those that became negative.

CONCLUSIONS Griseofulvin eradicates dermatophyte scalp carriage in less than one-half of preschool-aged children receiving between one and four 4-week courses of the drug.
Smoking Cessation Treatment for Adolescents
Authors: Karpinski Julie P. , Timpe Erin M. , Lubsch Lisa
Published: October 2020

Cigarette smoking in the adolescent population remains a public health concern. A significant portion of the adolescent population currently uses tobacco. Nicotine is particularly addicting in adolescents, and quitting is difficult. The goals for adolescent cigarette smoking efforts must include both primary prevention and smoking cessation. Bupropion and nicotine replacement therapies—including nicotine patches, gum, and nasal spray—have been studied to a limited extent in the adolescent population. Varenicline has not been evaluated as a treatment modality in adolescents. Long-term quit rates in the pharmacotherapy trials have not been optimal; however, decreases in cigarettes smoked per day have been observed. Several evidencebased guidelines include recommendations for smoking cessation in adolescents that include counseling and pharmacotherapy. Pharmacotherapy may be instituted for some adolescents in addition to counseling and behavioral interventions. Therapy should be individualized, based on smoking patterns, patient preferences, and concomitant disease states. Smoking cessation support for parents should be instituted as well. The pharmacist can play a large role in helping the adolescent quit smoking. Further studies evaluating pharmacotherapy options for smoking cessation in adolescents are necessary. If pharmacotherapy is used, it should be individualized and combined with psychosocial and behavioral interventions.
Respiratory Syncytial Virus Prophylaxis in Special Populations: Is it Something Worth Considering in Cystic Fibrosis and Immunosuppression?
Authors: Prescott William A. , Hutchinson David J.
Published: October 2020

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of infant hospitalization in the United States. Prophylaxis with palivizumab is effective in reducing RSV hospitalizations in premature infants and in infants or children with chronic lung disease or congenital heart disease. Patients with CF or those who are immunocompromised may be at increased risk for RSV infection–related complications; hence, prophylaxis may prove beneficial to these populations. The extent of palivizumab use in the CF and immunocompromised populations is variable. Palivizumab appears to be safe and may be effective in infants and young children with CF and immunocompromise. However, well-designed, randomized, controlled trials published in peer-reviewed journals are lacking, and its routine use can therefore not be recommended at this time. If used in patients with CF or those who are immunocompromised, RSV prophylaxis should be restricted to peak outbreak months in order to optimize the cost benefit of palivizumab.
Hyperphosphatemia in Pediatric Oncology Patients Receiving Liposomal Amphotericin B
Authors: Knoderer Chad A. , Knoderer Holly M.
Published: October 2020

OBJECTIVE

After transitioning our front-line amphotericin product to the liposomal formulation, we observed an increased incidence of hyperphosphatemia. We aimed to determine the incidence of hyperphosphatemia in children with oncologic disorders receiving an amphotericin B product and to establish whether the incidence varies depending on amphotericin formulation.

METHODS

This retrospective review of the medical record was conducted at a tertiary, free standing children's hospital. Pharmacy data revealed 159 patients receiving an amphotericin product between November 2006 and December 2008. Doses of amphotericin, serum phosphorous, calcium and creatinine concentrations were recorded at daily time points during the 10 days following both initiation and discontinuation of amphotericin. Administration of phosphate binders and total parenteral nutrition was noted. The incidence of hyperphosphatemia, defined as a serum value greater than the age-adjusted upper limit of normal, was compared among the amphotericin groups.

RESULTS

One hundred thirty-nine amphotericin recipients had a serum phosphorus measurement during amphotericin therapy. Final analysis included 117 children, of which 64 (55%) were oncology patients. Deoxycholate (mean maximum dose 1 mg/kg), lipid complex (mean maximum dose 4.8 mg/kg) and liposomal amphotericin (mean maximum dose 4.9 mg/kg) were used in 24 (20.5%), 37 (31.6%) and 56 (47.9%) of all patients, respectively. Hyperphosphatemia developed in 27% (32/117) of all patients, and in 33% (21/64) of oncology patients. Similar to within all recipients, among oncology patients, 45% (n=18) of liposomal recipients demonstrated hyperphosphatemia compared to 13% of those receiving lipid complex (n=3, p=0.007). No oncology patient received deoxycholate.

CONCLUSION

Nearly 45% of children with oncologic disorders receiving liposomal amphotericin developed hyperphosphatemia. The incidence is significantly greater for the liposomal formulation than either of the other amphotericin formulations.
Meperidine Restriction in a Pediatric Hospital
Authors: Benner Kim W. , Durham Spencer H.
Published: October 2020

BACKGROUND

Much has been published revealing concerns surrounding the use of meperidine due to associated toxicities, drug interactions, and lack of proven efficacy. Thus, many adult institutions have chosen to remove or limit the use of this agent, while little has been published about the restriction of meperidine in pediatrics. Many clinicians feel there are still clinical situations in which this agent may be useful.

OBJECTIVE

To describe methods taken in a pediatric hospital to restrict the use of meperidine and review literature describing uses of meperidine as a second-line agent.

METHODS

In our pediatric institution, a policy to restrict the use of meperidine was developed, approved, and implemented. An assessment of meperidine's use 6 months prior to policy implementation was done, along with a postinitiation review of use.

RESULTS

Data revealed that the use of meperidine dropped from 646 doses in 84 patients to 226 doses in 27 patients after restriction, as anticipated. Previous to implementation of these restrictions, orthopedics physicians ordered the majority of meperidine prescriptions, while the gastroenterology service ordered the majority of meperidine prescriptions after implementation of the restriction policy. However, the use of the required form was not widely adopted, with only 30% of practitioners utilizing it postrestriction. Widespread restriction of meperidine and education about use of the form at this institution are still under way.

CONCLUSION

Not only are there limited reasons for using meperidine, there are acceptable alternatives for every known indication. Limiting meperidine's use via a restriction policy and/or removal from the institution formulary can help limit the use of this potentially toxic agent in the pediatric patient.
Prophylactic Ketoconazole Shampoo for Tinea Capitis in a High-Risk Pediatric Population
Authors: Bookstaver P. Brandon , Watson Holly J. , Winters Shauna D. , Carlson Adrian L. , Schulz Richard M.
Published: October 2020

OBJECTIVES

Although topical agents for the treatment of tinea capitis decrease viable fungal elements and reduce shedding, their use as a prophylactic agent has not been investigated. This study evaluated the effectiveness of a prophylactic ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically evident tinea capitis infections in a high-risk African American, urban population.

METHODS

We conducted a retrospective analysis of a ketoconazole prophylaxis protocol that was implemented at an urban pediatric clinic for medically fragile children. Patients at high risk for tinea capitis received twice-weekly ketoconazole shampoo. The primary outcome of the study was a reduction in the number of documented tinea capitis infections between the 12-month preprotocol and 12-month postprotocol periods. A secondary outcome included the evaluation of predisposing risk factors for acquiring tinea infections.

RESULTS

Ninety-seven patients, with a mean age of 8.06 years, were included. Most patients (78%) were African American. There were a total of 13 tinea capitis infections during the 12-month preprotocol period. During the 12-month postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per-patient infections in the postprotocol period were 0.79 and 0.08 in the prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis did not reduce tinea capitis infections (p=NS). Previous history of infection and a high level of care were significant predictors of infections (p<0.05).

CONCLUSIONS

Improved hygiene, adherence to prescribed treatment regimens, and prevention of recurrent environmental exposure to surviving fomites should be stressed in high-risk patients and supersede the need for an antifungal (ketoconazole shampoo) prophylaxis protocol.
Common Sense Model of Illness in Youth With Type 1 Diabetes or Sickle Cell Disease
Authors: Huston Sally A. , Houk Christopher P.
Published: October 2020

OBJECTIVES

To qualitatively explore differences in Leventhal's common sense model (CSM) constructs between youth with type 1 diabetes (T1D) and sickle cell disease (SCD) and between different age groups and level of disease control.

METHODS

Two structured individual interviews were conducted in 24 youth with T1D (n=12) or SCD (n=12). Patients were between 8 and 21 years of age, had either good or poor disease control, and were seen at an outpatient children's hospital medical clinic.

RESULTS

Youth conceptualize their chronic disease in terms of identity, cause, timeline, control, and consequences: both cognitive and emotional dimensions are apparent. There was considerable contrast between discussions of youth with well- and poorly controlled T1D but little contrast between youth with well- and poorly controlled SCD. Surprisingly, youth with well-controlled T1D mentioned emotions most frequently. No youth with poorly controlled T1D described disease acceptance, but the majority of youth with well-controlled T1D did. Adolescents and young adults with good T1D control appear to understand disease cause, have better illness coherence, and habitually link discussion of symptoms and negative emotions with solutions. Youth with poorly controlled T1D appeared more likely to connect symptoms with negative consequences. Consequences included 1) disease symptoms, 2) the need to perform self-care activities, 3) physical outcomes, 4) health-system activities, 5) emotions, and 6) life impact. Interestingly, sickling crisis was mentioned more frequently by youth with good SCD control than by those with poor SCD control. Youth with SCD are distressed by others' judgmental perceptions and by feeling different from others.

CONCLUSIONS

In contrast to previous CSM work, youth with well-controlled T1D in this study discussed emotions more frequently than did those with poor control. Disease perceptions were similar between youth with well- and poorly controlled SCD. Results indicate there are noteworthy cognitive and emotional differences between youth with different types of disease and levels of disease control.
Development and Validation of Weight, Height and Age Bands to Guide the Prescription of Fixed-Dose Dispersible Tablet Formulations
Authors: Larson Charles P. , Sauvé Laura , Senkungu Jude Kimbowa , Arifeen Shams El , Brant Rollin
Published: October 2020

OBJECTIVES: Conversion of pediatric essential drugs from syrup to dispersible tablet formulations would require fixed dose options guided by the weight band in which a child falls or a proxy for weight, such as height or age. The purpose of this study was to determine whether weight, height, or age bands can be created that would lead to greater than 95% of children receiving a therapeutic dose of 6 commonly prescribed essential drugs, including paracetamol, iron sulfate, amoxicillin, co-trimoxazole (i.e., trimethoprim/sulfamethoxazole), ciprofloxacin, and co-artemether (i.e., artemether/lumefantrine).

METHODS: Using World Health Organization growth standards, we created 4 weight bands and then matched them to height and age 50th percentile growth curves. The resulting weight, height, and age bands were then applied to Ugandan and Bangladeshi anthropometric data sets, and the percentage of children who would have received a correct therapeutic dose based upon weight, height, or age was determined. This percentage was interpreted as acceptable if >95%, marginal if 90% to 95% and unacceptable if <90%.

RESULTS: Applying the 4 weight bands to the 6 selected drugs, greater than 95% of children would have received an acceptable therapeutic dose across the 4 weight bands for each of the 6 drugs tested. None of the drugs tested would deliver an acceptable therapeutic dose across all bands based upon height or age among Ugandan children, and only co-trimoxazole would have been delivered at acceptable therapeutic levels based upon these bands in Bangladeshi children.

CONCLUSIONS: For the 6 drugs tested, dispersible tablets prescribed on the basis of a 4-dose regimen determined by weight bands would deliver an acceptable therapeutic dose greater than 95% of the time. Substituting weight for age or height bands would result in unacceptable levels of under- or overdosing.
Levetiracetam in Neonatal Seizures: A Review
Authors: Mruk Allison L. , Garlitz Karen L. , Leung Noelle R.
Published: October 2020

Phenobarbital and phenytoin have been the mainstay treatment modalities for neonatal seizures. Studies have revealed these agents control seizures in less than half of neonates, can cause neuronal apoptosis in vitro, and have highly variable pharmacokinetics in neonates. In contrast, there have been no reports of levetiracetam causing these neurotoxic effects. Due to its favorable side effect and pharmacokinetic profiles and positive efficacy outcomes in neonatal studies to date, there is great interest in the use of levetiracetam for neonatal seizures. This article reviews the literature regarding the safety of levetiracetam in neonates and its efficacy in neonatal seizures.
Extended-Spectrum Beta-Lactamase Bacteria From Urine Isolates in Children
Authors: Degnan Lisa A. , Milstone Aaron M. , Diener-West Marie , Lee Carlton K. K.
Published: October 2020

OBJECTIVES: Multidrug-resistant Gram-negative bacteria, including extended-spectrum beta-lactamase (ESBL)–producing organisms, are a growing problem. The primary objective of this study was to describe the proportion of children with ESBL-producing urinary isolates at a tertiary medical center as well as these organisms' susceptibility patterns. The secondary objective was to identify the risk factors for acquiring ESBL urinary pathogens.

METHODS: This retrospective study evaluated a cohort of children with ESBL urinary isolates, admitted to a tertiary children's hospital during a 6-year period. The proportion of patients with an ESBL-producing urinary isolate among all patients who grew a Gram-negative isolate is described together with the organism's susceptibility pattern. Patients with non-ESBL Gram-negative urinary organisms were used as a control group for identifying patient risk factors for ESBL.

RESULTS: A total of 7.8% (29 of 370) of patients in our cohort grew Gram-negative urinary isolates with an ESBL strain. Most of the ESBL organisms isolated were sensitive to carbapenems (100% of ESBL organisms susceptible to ertapenem and 93.8% susceptible to meropenem) and amikacin (92.3% of ESBL organisms susceptible). Patients with longer hospitalization, recent antibiotic use, and recent intensive care unit admission were found to be at increased risk for ESBL organisms in the urine.

CONCLUSIONS: When selecting empiric antibiotic therapy for suspected urinary tract infection in children, it may be prudent to consider the risk factors identified for acquiring an ESBL urinary pathogen.
Effect of intermediate aerodisk mounted sharp tip spike on the drag reduction over a hemispherical body at Mach 2.0
Authors: Tembhurnikar Payal , Jadhav Akash , Sahoo Devabrata
Published: October 2020

Reduction of forebody drag in high speed flying vehicles such as rockets and missiles are of high research interest in the present time. In the present research, drag reduction obtained by using an intermediate aerodisk mounted sharp tip spike has been investigated using computational studies at Mach number of 2.0. The flowfield over a hemispherical blunt body with an intermediate aerodisk mounted sharp tip spike is investigated at zero degree angle of attack and the amount of drag reduction obtained is then compared with that of a conventional sharp tip spike mounted hemisphere. The presence of an intermediate aerodisk changes the flow physics and shock system over the blunt body. The change in the system of shock waves by mounting an intermediate aerodisk results in a higher percentage (20% higher) of drag reduction generated by the blunt spiked body moving at a supersonic speed of Mach 2.0. Use of intermediate aerodisk proves to be beneficial in terms of drag reduction for spike lengths ranging beyond the critical length.
Heat transfer and entropy generation for natural convection by adiabatic obstacles inside a cavity heated on the left side
Authors: Baliti Jamal , Hssikou Mohamed , Elguennouni Youssef , Moussaoui Ahmed , Alaoui Mohammed
Published: October 2020

By using finite difference method, the problem of heat transfer and entropy generation for natural convection of a fluid inside a square cavity with inner adiabatic bodies has been investigated numerically. Calculations have been made for Rayleigh numbers ranging from 102 to 5·104 for two obstacles with different heights. Results are presented as streamlines, isotherm contours and Nusselt number for Prandtl number of 0.71 (assuming the cavity is filled with air). The obtained results demonstrate the effects of pertinent parameters on the fluid flow, thermal fields and heat transfer inside the cavity. The results show that the heat transfer rates generally increase with the shrink of the obstacle size and with the increase of Rayleigh number. The entropy generation is higher at locations with large temperature gradients. Excellent agreement is obtained with previous results in the literature.
Double diffusion in square porous cavity subjected to conjugate heat transfer
Authors: Ahamad N. , Kamangar Sarfaraz , Aljohani A.F. , Azeem A , Ali Baig , Badruddin Irfan
Published: October 2020

Double diffusion inside a square porous cavity being subjected to conjugate heat transfer arising because of the square solid block at the center is studied under homogeneous properties. The double diffusive equations along with the conjugate effect due to square block are subjected to solution through finite element method (FEM). The right vertical surface of cavity remains at cool temperature (Tc) and concentration (Cc), whereas the hot temperature (Th) and higher concentration (Ch) is maintained at the left surface of the cavity. The investigated parameters considered are the Rayleigh number (Ra), Thermal conductivity ratio (Kr), Lewis number (Le), Buoyancy ratio (N) and the height of solid block (B). The outcomes are presented in terms of contours of concentration, isotherms and streamlines, along with local Sherwood number (Sh) and Nusselt number (Nu). The fluid is found to rush around the top left corner of solid. The mass transfer has sharp rise around the top left corner of the solid block.
Influence of variable particle size reinforcement on mechanical and wear properties of alumina reinforced 2014Al alloy particulate composite
Authors: Bharath V. , Ashita D.H. , Auradi V. , Nagaral Madeva
Published: October 2020

Al2O3 may be the most important reinforcement in aluminum-based composites that are rising quickly in modern years. The significance of this paper is to study the influence of Al2O3p size variation (i.e. 53 µm and 88 µm) and content (i.e. 9, 12, and 15Wt %) on density, hardness, tensile strength, elongation to fracture and wear studies. During the preparation of each composite, the ceramic reinforcements were introduced in a novel way which involves two-stage additions of reinforcements during liquid stirring. It has been found that because the size of the Al2O3p is reduced, measurement of the density showed that 2014Al-Al2O3p composites contained slight porosity and also the quantity of porosity among the prepared composites higher with diminishing the Al2O3p size and increasing weight percentage of Al2O3p. In addition to this, the results show that by decreasing the Al2O3p size and increasing the weight proportion of the Al2O3p the tensile strength and hardness of the prepared composites increase. Microstructural characterization carried out for the 2014Al-Al2O3 composites using scanning electron microscopy (SEM) which showed a fairly homogeneous distribution of Al2O3p with grain refinement of the matrix. Wear test is conducted for the prepared composites by utilizing a computerized pin on disc wear testing machine which shows greater wear resistance property as the size of the Al2O3p reduced.
Temaredaktørens forord: Danske grænser
Authors: Frandsen Steen Bo
Published: October 2020

Temanummeret fokuserer på danske grænser i anledning af hundredeåret for fastlæggelsen af den dansk-tyske landegrænse i Slesvig. Det forsøger at fremkalde billedet af grænsers mangfoldighed og foranderlighed og at understrege deres proceskarakter frem for det dominerende indtryk af noget fast og varigt. Et vigtigt udgangspunkt ligger i forskningen ved Center for Grænseregionsforskning, som siden 1976 har forsket i grænser, først nationalt, men siden stedse mere internationalt og komparativt. Temanummeret rækker med bidrag fra forskere fra andre discipliner og institutioner fra grænsernes historiske udvikling over de særlige omstændigheder i det arktiske område, på de sig gennem praksis forandrendegrænser mod Tyskland og Sverige samt de indre grænser i den offentlige debat.
Uden for tema: Privatisering for enhver pris? Drivkræfter og barrierer i privatiseringen af DONG 2001-2018
Authors: Brogaard Lena , Kestrup Jesper Dahl
Published: October 2020

Siden 1980 har den danske stat helt eller delvist frasolgt selskaber for et samlet provenu på over 80 mia. kr. (2017-priser). Privatiseringen af offentlige selskaber har blandt andet været drevet frem af ønsket om markedseffektivitet, politisk ideologi og EU-direktiver møntet på at fremme konkurrencen i det indre marked. På den baggrund undersøges det, hvorfor det tog over ti år at gennemføre en delvis privatisering af det statslige energi- og forsyningsselskab DONG (nu Ørsted). John Kingdons multiple streams-tilgang anvendes i et omfattende dokumentstudie til at indfange de kræfter, der i perioden 2001 til 2018 satte privatiseringen af DONG på den politiske dagsorden og bidrog til at forsinke og forandre beslutningen om at privatisere. Den drypvise privatisering af DONG blev dels formet af eksogene faktorer som international konkurrence, finanskrise og investeringsbanken Goldman Sachs, dels af den indsats, som skiftende regeringer, centraladministration og ledelsen i DONG lagde i at realisere privatiseringen.
Redaktionelt forord
Authors: Marcussen Martin
Published: October 2020

Center for Cybersecurity, der er placeret hos Forsvarets Efterretningstjeneste, lægger i deres årlige trusselvurdering ikke fingrene imellem: “Truslen fra cyberkriminalitet er MEGET HØJ”, slås fast med versaler i fed skrift. Cyberkriminalitet er en samlebetegnelse for handlinger, hvor hackere bruger cyberangreb til at begå kriminalitet, der er motiveret af et ønske om økonomisk berigelse. Også truslen fra cyberspionage er MEGET HØJ, konkluderer centeret. Det betyder konkret, at det er meget sandsynligt, at danske myndigheder og virksomheder vil blive udsat for forsøg på cyberspionage inden for de næste to år.
Offensive cyberoperasjoner: Den nye normalen?
Authors: Friis Karsten
Published: October 2020

Kan stater gå til motangrep om de blir angrepet digitalt i fredstid? Hva gjør toneangivende land, og hva sier internasjonal rett og normer om dette? Og hva kan de sikkerhetspolitiske konsekvensene bli av økt bruk av offensive cyberoperasjoner? Denne artikkelen diskuterer denne sikkerhetspolitiske utviklingen i kombinasjon med en analyse av det relevante internasjonale rettslige rammeverket. Artikkelen begynner med en redegjørelse av USAs nye tilnærming til offensive operasjoner, knytte til de to begrepene “persistent engagement” og “defend forward”. Deretter følger en kort case-studie på Norges tilnærming til offensive cyber operasjoner, noe som bringer oss til “Responsibility of States of International Wrongful Acts”-lovverket, som er det mest relevante med tanke på offensive cyberangrep utenom væpnet konflikt. Artikkelen avsluttes med en diskusjon av dilemmaer i skjøringspunktet sikkerhetspolitikk og folkerett.
Hvem er cybereksperten? Ekspertise og professioner i cybersikkerhedsfeltet
Authors: Willers Johann Ole
Published: October 2020

Cybersikkerhedseksperter spiller en vigtig rolle i at identificere digitale risici og at definere hensigtsmæssige løsninger. Denne artikel gør brug af professions- og ekspertsociologien til at belyse konkurrerende epistemiske rationaliteter i konstruktionen af digitale risici. På baggrund af et nyt datasæt omhandlende ekspertprofiler i offentlige og private cybersikkerhedsråd og -udvalg, argumenteres der for, at profilen af cybersikkerhedseksperter har bevæget sig væk fra et rent teknisk fokus og hen imod en procesorientering, som både er bredere i fokus og placeret tættere på beslutningstagere. Den nye ekspertprofil er positioneret i et spændingsfelt imellem tekniske, organisatoriske og økonomiske rationaliteter. I fraværet af en bred politisk debat kan denne udvikling styrke ekspertmagten, som nu er begrænset til få hybride aktører, som formår at bygge bro imellem de forskellige rationaliteter. En sådan udvikling vil være skadelig for demokratiet, men udviklingen imod en procesorienteret forståelse af cybersikkerhed åber samtidlig muligheder for at re-politisere cybersikkerhedsdiskursen igennem en mindre teknifiseret debat.
Abstracts
Authors: Jensen Mikkel Storm , Friis Karsten , Jacobsen Jeppe Teglskov , Willers Johann Ole , Lentz Lene Wacher , Pedersen Jens Myrup , Olesen Finn , Erbas Mina , Suenson Emil Lobe Wellington , Larsen Bøje
Published: October 2020

Abstracts of each article
Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards
Authors: Shapiro Julie Teresa , Leboucher Gilles , Myard-Dury Anne-Florence , Girardo Pascale , Luzzati Anatole , Mary Mélissa , Sauzon Jean-François , Lafay Bénédicte , Dauwalder Olivier , Laurent Frédéric , Lina Gerard , Chidiac Christian , Couray-Targe Sandrine , Vandenesch François , Flandrois Jean-Pierre , Rasigade Jean-Philippe
Published: October 2020

Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and between-ward patient transfers (or connectivity) impact population-level AMR in hospital networks can help optimize antibiotic stewardship and infection control strategies. Here, we used a metapopulation framework to explain variations in the incidence of infections caused by seven major bacterial species and their drug-resistant variants in a network of 357 hospital wards. We found that ward-level antibiotic consumption volume had a stronger influence on the incidence of the more resistant pathogens, while connectivity had the most influence on hospital-endemic species and carbapenem-resistant pathogens. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data provide evidence that both antibiotic use and connectivity measurably influence hospital AMR. Finally, we provide a ranking of key antibiotics by their estimated population-level impact on AMR that might help inform antimicrobial stewardship strategies.
Drosophila PDGF/VEGF signaling from muscles to hepatocyte-like cells protects against obesity
Authors: Ghosh Arpan C , Tattikota Sudhir Gopal , Liu Yifang , Comjean Aram , Hu Yanhui , Barrera Victor , Ho Sui Shannan J , Perrimon Norbert
Published: October 2020

PDGF/VEGF ligands regulate a plethora of biological processes in multicellular organisms via autocrine, paracrine, and endocrine mechanisms. We investigated organ-specific metabolic roles of Drosophila PDGF/VEGF-like factors (Pvfs). We combine genetic approaches and single-nuclei sequencing to demonstrate that muscle-derived Pvf1 signals to the Drosophila hepatocyte-like cells/oenocytes to suppress lipid synthesis by activating the Pi3K/Akt1/TOR signaling cascade in the oenocytes. Functionally, this signaling axis regulates expansion of adipose tissue lipid stores in newly eclosed flies. Flies emerge after pupation with limited adipose tissue lipid stores and lipid level is progressively accumulated via lipid synthesis. We find that adult muscle-specific expression of pvf1 increases rapidly during this stage and that muscle-to-oenocyte Pvf1 signaling inhibits expansion of adipose tissue lipid stores as the process reaches completion. Our findings provide the first evidence in a metazoan of a PDGF/VEGF ligand acting as a myokine that regulates systemic lipid homeostasis by activating TOR in hepatocyte-like cells.
Specificity in glycosylation of multiple flagellins by the modular and cell cycle regulated glycosyltransferase FlmG
Authors: Ardissone Silvia , Kint Nicolas , Viollier Patrick H
Published: October 2020

How specificity is programmed into post-translational modification of proteins by glycosylation is poorly understood, especially for O-linked glycosylation systems. Here we reconstitute and dissect the substrate specificity underpinning the cytoplasmic O-glycosylation pathway that modifies all six flagellins, five structural and one regulatory paralog, in Caulobacter crescentus, a monopolarly flagellated alpha-proteobacterium. We characterize the biosynthetic pathway for the sialic acid-like sugar pseudaminic acid and show its requirement for flagellation, flagellin modification and efficient export. The cognate NeuB enzyme that condenses phosphoenolpyruvate with a hexose into pseudaminic acid is functionally interchangeable with other pseudaminic acid synthases. The previously unknown and cell cycle-regulated FlmG protein, a defining member of a new class of cytoplasmic O-glycosyltransferases, is required and sufficient for flagellin modification. The substrate specificity of FlmG is conferred by its N-terminal flagellin-binding domain. FlmG accumulates before the FlaF secretion chaperone, potentially timing flagellin modification, export, and assembly during the cell division cycle.
Finding phenazine
Authors: Wolfson Sarah J , Kelly Libusha
Published: October 2020

Analysis of genetic information from soil samples provides insights into bacteria that help to protect crops from fungal diseases by producing chemicals called phenazines.
Novel targets for engineering Physostegia chlorotic mottle and tomato brown rugose fruit virus-resistant tomatoes: in silico prediction of tomato microRNA targets
Authors: Gaafar Yahya Zakaria Abdou , Ziebell Heiko
Published: October 2020

Background

Physostegia chlorotic mottle virus (PhCMoV; genus: Alphanucleorhabdovirus, family: Rhabdoviridae) and tomato brown rugose fruit virus (ToBRFV; genus: Tobamovirus, family: Virgaviridae) are newly emerging plant viruses that have a dramatic effect on tomato production. Among various known virus-control strategies, RNAi-mediated defence has shown the potential to protect plants against various pathogens including viral infections. Micro(mi)RNAs play a major role in RNAi-mediated defence.

Methods

Using in silico analyses, we investigated the possibility of tomato-encoded miRNAs (TomiRNA) to target PhCMoV and ToBRFV genomes using five different algorithms, i.e., miRanda, RNAhybrid, RNA22, Tapirhybrid and psRNATarget.

Results

The results revealed that 14 loci on PhCMoV and 10 loci on ToBRFV can be targeted by the TomiRNAs based on the prediction of at least three algorithms. Interestingly, one TomiRNA, miR6026, can target open reading frames from both viruses, i.e., the phosphoprotein encoding gene of PhCMoV, and the two replicase components of ToBRFV. There are currently no commercially available PhCMoV- or ToBRFV-resistant tomato varieties, therefore the predicted data provide useful information for the development of PhCMoV- and ToBFRV-resistant tomato plants.
The Bacteria Genome Pipeline (BAGEP): an automated, scalable workflow for bacteria genomes with Snakemake
Authors: Olawoye Idowu B. , Frost Simon D.W. , Happi Christian T.
Published: October 2020

Next generation sequencing technologies are becoming more accessible and affordable over the years, with entire genome sequences of several pathogens being deciphered in few hours. However, there is the need to analyze multiple genomes within a short time, in order to provide critical information about a pathogen of interest such as drug resistance, mutations and genetic relationship of isolates in an outbreak setting. Many pipelines that currently do this are stand-alone workflows and require huge computational requirements to analyze multiple genomes. We present an automated and scalable pipeline called BAGEP for monomorphic bacteria that performs quality control on FASTQ paired end files, scan reads for contaminants using a taxonomic classifier, maps reads to a reference genome of choice for variant detection, detects antimicrobial resistant (AMR) genes, constructs a phylogenetic tree from core genome alignments and provide interactive short nucleotide polymorphism (SNP) visualization across core genomes in the data set. The objective of our research was to create an easy-to-use pipeline from existing bioinformatics tools that can be deployed on a personal computer. The pipeline was built on the Snakemake framework and utilizes existing tools for each processing step: fastp for quality trimming, snippy for variant calling, Centrifuge for taxonomic classification, Abricate for AMR gene detection, snippy-core for generating whole and core genome alignments, IQ-TREE for phylogenetic tree construction and vcfR for an interactive heatmap visualization which shows SNPs at specific locations across the genomes. BAGEP was successfully tested and validated with Mycobacterium tuberculosis (n = 20) and Salmonella enterica serovar Typhi (n = 20) genomes which are about 4.4 million and 4.8 million base pairs, respectively. Running these test data on a 8 GB RAM, 2.5 GHz quad core laptop took 122 and 61 minutes on respective data sets to complete the analysis. BAGEP is a fast, calls accurate SNPs and an easy to run pipeline that can be executed on a mid-range laptop; it is freely available on: https://github.com/idolawoye/BAGEP.
Developing mathematical model for diurnal dynamics of photosynthesis in Saccharum officinarum responsive to different irrigation and silicon application
Authors: Verma Krishan K. , Wu Kai-Chao , Verma Chhedi Lal , Li Dong-Mei , Malviya Mukesh Kumar , Singh Rajesh Kumar , Singh Pratiksha , Chen Gan-Lin , Song Xiu Peng , Li Yang Rui
Published: October 2020

In the dynamic era of climate change, agricultural farming systems are facing various unprecedented problems worldwide. Drought stress is one of the serious abiotic stresses that hinder the growth potential and crop productivity. Silicon (Si) can improve crop yield by enhancing the efficiency of inputs and reducing relevant losses. As a quasi-essential element and the 2nd most abundant element in the Earth’s crust, Si is utilized by plants and applied exogenously to combat drought stress and improve plant performance by increasing physiological, cellular and molecular responses. However, the physiological mechanisms that respond to water stress are still not well defined in Saccharum officinarum plants. To the best of our knowledge, the dynamics of photosynthesis responsive to different exogenous Si levels in Saccharum officinarum has not been reported to date. The current experiment was carried out to assess the protective role of Si in plant growth and photosynthetic responses in Saccharum officinarum under water stress conditions. Saccharum officinarum cv. ‘GT 42’ plants were subjected to drought stress conditions (80–75%, 55–50% and 35–30% of soil moisture) after ten weeks of normal growth, followed by the soil irrigation of Si (0, 100, 300 and 500 mg L−1) for 8 weeks. The results indicated that Si addition mitigated the inhibition in Saccharum officinarum growth and photosynthesis, and improved biomass accumulation during water stress. The photosynthetic responses (photosynthesis, transpiration and stomatal conductance) were found down-regulated under water stress, and it was significantly enhanced by Si application. No phytotoxic effects were monitored even at excess (500 mg L−1). Soil irrigation of 300 mg L−1 of Si was more effective as 100 and 500 mg L−1 under water stress condition. It is concluded that the stress in Saccharum officinarum plants applied with Si was alleviated by improving plant fitness, photosynthetic capacity and biomass accumulation as compared with the control. Thus, this study offers new information towards the assessment of growth, biomass accumulation and physiological changes related to water stress with Si application in plants.
An improved modified early warning score that incorporates the abdomen score for identifying multiple traumatic injury severity
Authors: Jiang Xiaobin
Published: October 2020

Background

Rapid identification of trauma severity is essential for the timely triage of multiple trauma patients. Tools such as the modified early warning score (MEWS) are used for determining injury severity. Although the conventional MEWS is a good predictor of mortality, its performance assessing injury severity is moderate. This study hypothesized that adding an injury site severity-related score (e.g., abdomen score) may enhance the capability of the MEWS for identifying severe trauma.

Method

To validate the hypothesis, we propose an improved modified early warning score called MEWS-A, which incorporates an injury site-specific severity-related abdomen score to MEWS. The utility of MEWS and MEWS-A were retrospectively evaluated and compared for identifying trauma severity in adult multiple trauma patients admitted to the emergency department.

Results

We included 1,230 eligible multiple trauma patients and divided them into minor and severe trauma groups based on the injury severity score. Results of logistic regression and receiver operating characteristic (ROC) curve analyses showed that the MEWS-A had a higher area under the ROC curve (AUC: 0.81 95% CI [0.78–0.83]) than did the MEWS (AUC: 0.77 95% CI [0.74–0.79]), indicating that the MEWS-A is superior to the MEWS in identifying severe trauma. The optimal MEWS-A cut-off score is 4, with a specificity of 0.93 and a sensitivity of 0.54. MEWS-A ≥ 4 can be used as a protocol for decision-making in the emergency department.

Conclusions

Our study suggests that while the conventional MEWS is sufficient for predicting mortality risk, adding an injury site-specific score (e.g., abdomen score) can enhance its performance in determining injury severity in multiple trauma patients.
Chemical Composition of Diplopterys pubipetala (Malpighiaceae)
Authors: Costa Mariana de O. N. , Santos Kamylla T. , Almeida Clarice A. , Fonseca Francine S. A. da , Angolini Célio F. F. , Oliveira Dario A. de , Júnior Afrânio F. de Melo , Menezes Elytania V. , Royo Vanessa de A.
Published: October 2020

In view of the therapeutic potential and popular use of the Malpighiaceae family, with emphasis on the importance of species of the Diplopterys (Banisteriopsis) genus, the objective of this study was to identify the metabolites classes of leaves and stems of Diplopterys pubipetala. The extracts were analyzed and detected 10 compounds distributed among alkaloids (2), flavonoids (3), terpenes (3), saponin (1) and lactone (1). Among the substances found, there are compounds already reported in the Malpighiaceae family. The therapeutic potentials cited in the literature for the identified substances were: antifungal, antiviral, antimicrobial, antioxidant, anti-inflammatory and antitumor actions. This work is a pioneer in the study of the chemical constituents present in D. pubipetala and opens new lines of research for this species.