bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Expenditure in Reproductive Effort of Male and Female Killdeer (Charadrius vociferus)
Authors: Brunton Dianne H.
Published: September 2019

The reproductive investment strategies of the sexes during the breeding season are detailed for Killdeer (Charadrius vociferus), a monogamous plover. I measured the energy investments of the sexes in reproductive, mating, and parental effort. As predicted, males expend more mating effort than females; however, the sexes expend equal amounts of parental effort. Total energy expenditure in reproductive effort (mating and parental effort) during a successful nesting attempt was also equal for the sexes. However, early parental effort expenditures by females, early mating effort expenditures by males, and high rates of nest failure combine to result in female reproductive energy expenditures being significantly higher over the breeding season. This suggests that energy expenditure alone is not adequate for accurate comparisons of the relative investments of the sexes. Studies investigating male and female investments need to consider the degree and pattern of nest failures along with patterns of energy expenditure.

The advantages to male and female Killdeer of sharing parental care is demonstrated using adult removal experiments. In general, a deserted parent expends more energy in parental effort than a bi-parental parent and has significantly lower reproductive success. However, males are able to hatch chicks, whereas females lose or abandon their nests within a few days of mate removal. Thus, monogamy in Killdeer appears to result from high nest failure rates, the necessity of two parents for any reproductive success, and the generalizable nature of Killdeer parental care.
Winter Survival and Territory Acquisition in a Northern Population of Black-Capped Chickadees
Authors: Desrochers André , Hannon Susan J. , Nordin Kelly E.
Published: September 2019

We assessed the effects of winter food supplementation on differential survival between sex, age and dominance classes, and the effects of feeding and territorial defense on breeding density in a northern population of Black-capped Chickadees (Parus atricapillus). Survival rates were higher in a food-supplemented area than in a control area, which suggests that food abundance limited winter survival. Survival was greater among males than lower-ranking females in 1 of 2 years, and greater in dominants than in subordinates, within sex and age classes. Survival of adults and first-year birds, however, did not differ significantly. In the 2 years of this study, a sharp decline of population size occurred at the onset of territoriality in spring. Birds that disappeared in spring were mainly subordinates of each sex. Breeding densities in control and feeder areas were similar in the two years. Eight of 14 territorial birds removed in 2 years were replaced, implying that a nonbreeding surplus was present in early spring.
Phylogenomic Analysis Reveals the Evolutionary Route of Resistant Genes in Staphylococcus aureus
Authors: John Jiffy , George Sinumol , Nori Sai Ravi Chandra , Nelson-Sathi Shijulal
Published: September 2019

Multidrug-resistant Staphylococcus aureus is a leading concern worldwide. Coagulase-Negative Staphylococci are claimed to be the reservoir and source of important resistant elements in S. aureus. However, the origin and evolutionary route of resistant genes in S. aureus are still remaining unknown. Here, we performed a detailed phylogenomic analysis of 152 completely sequenced S. aureus strains in comparison with 7,529 non-Staphylococcus aureus reference bacterial genomes. Our results reveal that S. aureus has a large open pan-genome where 97 (55%) of its known resistant-related genes belonging to its accessory genome. Among these genes, 47 (27%) were located within the Staphylococcal Cassette Chromosome mec (SCCmec), a transposable element responsible for resistance against major classes of antibiotics including beta-lactams, macrolides, and aminoglycosides. However, the physically linked mec-box genes (MecA–MecR–MecI) that are responsible for the maintenance of SCCmec elements is not unique to S. aureus, instead it is widely distributed within Staphylococcaceae family. The phyletic patterns of SCCmec-encoded resistant genes in Staphylococcus species are significantly different from that of its core genes indicating frequent exchange of these genes between Staphylococcus species. Our in-depth analysis of SCCmec-resistant gene phylogenies reveals that genes such as blaZ, ble, kmA, and tetK that are responsible for beta-lactam, bleomycin, kanamycin, and tetracycline resistance in S. aureus were laterally transferred from non-Staphylococcus sources. In addition, at least 11 non-SCCmec-encoded resistant genes in S. aureus, were laterally acquired from distantly related species. Our study evidently shows that gene transfers played a crucial role in shaping the evolution of antibiotic resistance in S. aureus.
Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity
Authors: Worawongsakul Rasin , Sirachainan Nongnuch , Rojanawatsirivej Apimid , Boongird Atthaporn , Singhsnaeh Arunee , Swangsilpa Thiti , Dhanachai Mantana , Puataweepong Putipun , Ruangkanchanasetr Rawee , Pakakasama Samart , Anurathapan Usanarat , Songdej Duantida , Pongphitcha Pongpak , Khongkhatithum Chaiyos , Hansasuta Ake , Thokanit Nintita Sripaiboonkij , Lusawat Apasri , Yuthagovit Sarunya , Thammachantha Samasuk , Muangruk Danupon , Hongeng Suradej
Published: September 2019

Background

Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity.

Methods

The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test.

Results

Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%).

Conclusions

Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.
P01 Incidence of juvenile idiopathic arthritis in the United Kingdom: estimates from a national primary care dataset
Authors: Costello Ruth , McDonagh Janet , Dixon Will , Hyrich Kimme , Humphreys Jenny
Published: September 2019

Poster presentation Tuesday 8 October

Background

Juvenile idiopathic arthritis (JIA) is the most common childhood onset inflammatory arthritis. The last estimates of incidence of JIA in the UK are from nearly 30 years ago, prior to international classification consensus and the emergence of paediatric and adolescent rheumatology as a specialty. The aim of this study was to estimate incidence of JIA from primary care records in the UK since 2000.

Methods

The study used data from the Clinical Practice Research Datalink (CPRD), a database of UK primary care records broadly representative of the UK in terms of age, gender and ethnicity. A pre-defined list of JIA Read codes were used to identify incident cases annually from 2000-2018. Incidence rates (IR) with 95% confidence intervals(CI) were calculated and stratified by age and gender. The denominator was the population of CPRD <16 years old on the 31st December each year. Direct standardisation, applying Office for National Statistics population data, was used to estimate the UK IR. IRs in 5-year groupings were calculated 2000-2015 to identify change over time.

Results

Between 2000-2018, there were 1927 incident cases of JIA, from a total of 23,328,676 children <16 years old in CPRD. The total IR (95% CI) was 8.26 (7.90-8.64) per 100,000 population; for females and males respectively it was 9.83 (9.27-10.43) and 6.78 (6.33-7.27) per 100,000. Age-adjusted direct standardisation to the UK population estimated a total IR of 9.66 per 100,000 person-years. By age group, there appeared to be a lower incidence in middle childhood compared to early childhood and adolescents, as well as infancy where lower rates may be due to difficulties recognising the disease (Table 1). IRs over time did not appear to change.

P01 Table 1: Incidence rates by age group Age (years) Denominator Cases IR (95% CI) Per 100,000 0-2 1739417 113 6.5 (5.40-7.81) >2-6 5763003 534 9.27 (8.51 – 10.08) >6-12 9464988 693 7.32 (6.80-7.90) >12-15 6361268 587 9.22 (8.51-10.01)

Conclusion

This is the first study to provide contemporary UK estimates of the incidence of JIA for nearly 30 years. JIA was more common in females compared to males, and in early childhood and adolescence compared to other age groups. Incidence appeared to be stable over fifteen years. These data provide important information for patients, their families and healthcare providers; in addition, they are vital for appropriate resource planning and service provision in paediatric and adolescent rheumatology.

Conflicts of Interest

The authors declare no conflicts of interest.
P29 Etanercept and IBD: can we identify at risk patients?
Authors: Shepherd Kathryn , Pai Nandita , Adams Daniella , Wilkinson Nick , Shivamurthy Vinay
Published: September 2019

Poster presentation Tuesday 8 October

Background

We present four cases of patients on etanercept treatment for juvenile idiopathic arthritis (JIA) subsequently diagnosed with inflammatory bowel disease (IBD). We hypothesise that there may be identifiable characteristics of these patients which makes them more identifiable to the physician.

Etanercept is a recombinant dimer of human tumour necrosis factor (TNF) receptor proteins bound to human IgG1. It is an effective second line treatment option in JIA for those who have failed, or are intolerant to, methotrexate, and an effective first line treatment option in those who have axial disease at diagnosis. Anti-TNF treatments are effective in IBD, however etanercept in particular does not have therapeutic benefit, and in one trial there was a non-significant trend towards worsening of disease.

Methods

Please refer to the Results section.

Results

Four cases, in a 15 year old male, 11 year old female, 10 year old female and 11 year old female, have been identified at our site. The time from etanercept initiation and diagnosis of IBD was between 2 weeks and 2 years 1 month. None of the cases had gastrointestinal symptoms at JIA diagnosis. All four were ANA negative, and in the two with information, both were HLA-B27 negative. Three out of four had hip arthritis involvement. There was a family history of IBD (ulcerative colitis) in only one of the cases. Aside from non-steroidal anti-inflammatory medications, there were no other immunomodulatory medications concurrently being taken in any of the cases while on etanercept. All four were anaemic (Hb < 120g/L) at diagnosis of IBD. Only one had raised ESR (43mm/hr) while all had normal CRP. Albumin was low in two (17g/L and 29g/L). Following gastroenterology review and endoscopy, two cases were diagnosed with Crohn’s disease and two with ulcerative colitis.

Conclusion

It remains unclear whether etanercept plays a role in the development of IBD in these patients, whether it unmasks subclinical disease, or whether there is no association and it is simply a coincidence. However, there continue to be case reports and series suggesting an association between the two. We hope to identify further cases similar to these from sources such as the UK Biologics Registry and via surveys from teams at paediatric rheumatology centres throughout the UK. Further to the identification of cases, a retrospective review of patient characteristics will be carried out. This may allow for further determination of identifiable characteristics for these patients, and therefore suggest a subgroup of JIA patients with a higher risk of developing IBD, in which case caution when considering etanercept treatment would be advised.

Conflicts of Interest

The authors declare no conflicts of interest.
P02 Multi-trajectories of disease activity in juvenile idiopathic arthritis
Authors: Shoop-Worrall Stephanie , Hyrich Kimme , Wedderburn Lucy , Thomson Wendy , Geifman Nophar
Published: September 2019

Background

Composite disease scores in juvenile idiopathic arthritis (JIA), such as the clinical Juvenile Arthritis Disease Activity Score (cJADAS), include multiple disease manifestations, presented as a single score. These overall scores aid understanding of disease holistically in each child or young person (CYP), and have been suggested as outcomes for clinical trials and targets in treat to target clinical strategies. However, signs and symptoms of disease may not follow similar patterns following a JIA diagnosis. It is not currently known what the patterns of disease activity are in CYP with JIA and how these cluster over time.

Methods

CYP with JIA were selected if enrolled in the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort, before January 2015. cJADAS10 components (active joint count 0-10, physician global, patient/parent global) were collected at diagnosis, six months, one year and then annually to three years.

Multivariate group-based trajectory models modelled cJADAS10 component scores using censored-normal (physician and parent global) and zero-inflated Poisson (active joint count) distributions. Within linear, quadratic and cubic polynomials, one to ten trajectories were tested. The optimal models were selected using Bayesian Information Criteria, model parsimony and clinical plausibility.

Results

Of 1,183 CYP selected, the majority were female (65%) and of white ethnicity (90%) with oligoarticular JIA the most common JIA category (45%).

The optimal model identified six multivariate patterns of disease. In four of these clusters, signs and symptoms of disease had similar patterns over time: Low-Remission (32%), Low-Low (20%), High-Low (16%) and High-Low-High (10%). However, in two groups, Low-Chronic (14%) and High Chronic (8%), manifestations of inflammation and wellbeing followed different trajectory severities and shapes over time. These groups demonstrated persistent poor wellbeing despite control of inflammatory signs.

Conclusion

Disease activity in CYP with JIA does not improve in a uniform manner following initial presentation to paediatric rheumatology. Six latent multivariate trajectories have been identified in young people with JIA, two of which persist with chronic poor wellbeing despite lowered inflammation.

Conflicts of Interest

The authors declare no conflicts of interest.
P09 Juvenile osteochondritis dissecans in juvenile idiopathic arthritis: a case series review
Authors: Ward Oliver , Leach Samantha , McMahon Anne-Marie , Tattersall Rachel S. , Nicolaou Nicolas , Hawley Daniel
Published: September 2019

Background

Juvenile osteochondritis dissecans (JOCD) is a condition of bone and cartilage lesions. Contributory factors may include ischaemia, trauma, genetic or biomechanical factors such as abnormal joint loading. Children and young people (CYP) with juvenile idiopathic arthritis (JIA) have low physical activity levels, present with joint abnormalities and are exposed to immunosuppression including steroids which may cause reduced bone density. Here we describe JOCD in CYP with JIA in our service.

Methods

Retrospective reviews of case notes were conducted for current CYP with JIA in our service with known JOCD, detailing: JIA diagnosis Age & BMI at diagnosisSymptom duration pre-diagnosisManagement (including steroids)JOCD diagnosis Age & BMI at diagnosisImagingManagement

Results

Table 1 summarises the results. Twelve (n = 10 female) CYP in our cohort of 270 had JOCD with 20 lesions diagnosed on magnetic resonance imaging (MRI). Polyarticular (n = 4) and extended oligoarticular (n = 5) were the commonest JIA sub-types with all CYP receiving systemic therapy and 75% (n = 9) requiring more than one biologic.

Mean symptom duration before JIA diagnosis was 6 months (range: 1-24 months) with a mean age of 6.5 years (range: 1.5-13 years). Mean time to JOCD diagnosis was 5.5 years (range: 1.5-10.25 years) with a mean age of 12 years (range: 8-17 years) and 7 CYP having a high BMI (>85th percentile for age). The mean number of previous steroid injections per JOCD joint was 4 (range: 0-17) compared with 3 (range: 0-8) in the non-JOCD joint. Talar dome lesions (n = 9) were commonest, followed by femoral condyle (n = 4 medial, n = 3 lateral). Initial management was conservative, with half (n = 10) requiring surgery. P09 Table 1

Conclusion

This review identifies that 4% (n = 12/270) of our CYP with JIA have known JOCD, compared with 0.03% (n = 29/100,000) of the general population. Risk factors appear to be polyarticular disease, exposure to ≥ 4 steroid injections per joint, biologic-resistant disease and high BMI with low physical activity. Where CYP with JIA report symptoms which do not fit an inflammatory pattern there should be a low threshold to consider JOCD, with prospective research needed to better understand the relationship between JOCD and JIA.

Conflicts of Interest

The authors declare no conflicts of interest.
P17 What is the experience of pain pre- and post intra-articular steroid injections in children and young people with juvenile idiopathic arthritis?
Authors: Bull Samantha , Hawley Daniel , Lee Helen , Armstrong Shirley , Peech Francesca , Edgerton Jenny , Leach Samantha , Nash Clare , McMahon Anne-Marie
Published: September 2019

Background

A rheumatology service evaluation was carried out in 2016 whereby we sought to understand whether children and young people (CYP) are receiving appropriate pain relief post-administration of steroid intra-articular injections (IAI’s) and whether extended time waiting for IAI’s increases CYP experience of pain.

The British Society for Rheumatology BSPAR section Standard of Care for children and young people with JIA recommends 4 weeks or less waiting time for steroid IAI under general anaesthetic (GA) and 10 days or less for steroid IAI under entonox.

Methods

Data collection was obtained by patient questionnaire over a 4-month period. Parents/carers and CYP were asked to complete a questionnaire pre-steroid IAI (by a member of staff on the day of the IAI) and the same questionnaire post-steroid IAI (by telephone by the author within 2 weeks of the date of the IAI).

Twenty parents/carers or CYP completed the questionnaires. Sixteen of the CYP were female and 4 were male. Median age was 3 years. Eighty percent had a diagnosis of oligoarticular juvenile idiopathic arthritis (JIA). Seventy-five percent had IAI’s under GA and 25% with Entonox. Fifty-four percent had knee(s) injected and 23.5% had ankle(s) injected.

Results

Sixty percent of CYP waited for 4 weeks or less for steroid IAI under GA. Twenty percent of CYP waited for less than 10 days for steroid IAI under entonox. The range of pain scores for CYP pre IAI was 0-10 and the median was 5. Post IAI the range of pain scores was 0-8 and the median was 3. A positive correlation was found between those waiting longer for IAI’s and higher pain scores.

P17 Table 1: CYP experience of pain Pre IAI Post IAI Pain in joints injected or due to be injected 95% 55% CYP taking pain medication 85% 55% Type of pain medication: Diclofenac 10% 10% Ibuprofen 25% 10% Naproxen 5% 5% Naproxen & codeine 5% 0% Naproxen & oramorph 0% 5% Paracetamol 10% 10% Paracetamol & ibuprofen 30% 15% None 15% 40% Refusing 0% 5% General activity affected 90% 60% Pain medication required 80% 50% Pain medication effective 80% (100% of CYP requiring medication) 50% (100% of CYP requiring medication)

Conclusion

In our small cohort, fifty percent of CYP required no pain medication post-IAI, and fifty percent of CYP who did require pain medication post-IAI perceived the pain medication they were receiving was adequate (Table 1).

A positive correlation was found between CYP waiting longer for IAI’s and CYP experiencing higher pain scores therefore, accepting our modest sample size, this service evaluation supports ensuring timely access to IAI and the avoidance of longer waiting times.

Conflicts of Interest

The authors declare no conflicts of interest.
Risk Factors for Dry Eye After Refractive Surgery
Authors: Shehadeh-Mashor Raneen , Mimouni Michael , Shapira Yinon , Sela Tzahi , Munzer Gur , Kaiserman Igor
Published: September 2019

Purpose:

To determine the factors associated with clinically significant dry eye after keratorefractive surgery.

Methods:

This is a large database retrospective study that included consecutive cases of myopic laser in situ keratomileusis (LASIK) or photorefractive keratectomy performed between 2008 and 2016 at Care-Vision Laser Center, Israel. Patients were divided into 2 groups according to whether they developed clinically significant dry eye.

Results:

A total of 25,317 right eyes of 25,317 patients, with a mean age of 27.0 ± 8.3 years, were included. Postoperative dry eye developed in 1518 eyes (6.0%). The dry eye group was older (29.2 ± 9.0 vs. 27.6 ± 8.3 yrs, P < 0.001) and had a higher proportion of women (48.5% vs. 44.8%, P = 0.005), lower preoperative spherical equivalent (3.7 ± 2.0 vs. 4.0 ± 2.3D, P < 0.001), lower preoperative best-corrected visual acuity (0.019 ± 0.057 vs. 0.016 ± 0.064 Logarithm of the Minimum Angle of Resolution (LogMAR), P = 0.04), and lower proportion of preoperative soft contact lens wearers (40.6% vs. 45.5%, P < 0.001). In the postoperative dry eye group, a high proportion underwent LASIK (52.4% vs. 38.7%, P < 0.001) and were treated with a 7.0-mm (as opposed to 6.0 mm) optic zone (18.9% vs. 16.3%, P < 0.001). In multivariable analysis, older age [odds ratio (OR) 1.013, P < 0.001], female gender (OR 0.87, P = 0.009), lower preoperative refractive error (OR 1.05, P < 0.001), and LASIK (OR 0.67, P < 0.001) were associated with postoperative dry eye.

Conclusions:

Patients who are of older age, are of female gender, and have a lower preoperative refractive error and those undergoing LASIK are more likely to develop dry eye disease after keratorefractive surgery.
The Weekend Effect in Older Adult Urosepsis Admissions
Authors: Peach Brian C. , Li Yin , Cimiotti Jeannie P.
Published: September 2019

Background:

Urosepsis is common in older adults with more infections identified as community-acquired as opposed to hospital-acquired. Despite the prevalence of urosepsis and its high mortality rates, very little is known about the care outcomes of older adult patients with community-acquired urosepsis who are admitted to the hospital on a weekend.

Objectives:

To determine if a weekend admission was associated with inpatient mortality in older adults admitted to an acute care hospital with a diagnosis of community-acquired urosepsis.

Methods:

Data from the State Inpatient Datasets for Florida were merged with data from the American Hospital Association Annual Survey on hospital characteristics for the year 2014. Logistic regression models with a sizable number of patient and hospital controls were used to identify factors associated with inpatient mortality in patients 65 years of age and older with a primary or secondary diagnosis of community-acquired urosepsis.

Results:

In total 21,904 older adults were admitted to a Florida hospital with a diagnosis of community-acquired urosepsis; 5736 of these patients were admitted on a weekend. In a fully adjusted logistic regression model, weekend admission was associated with a 12% increase in the odds of mortality, and each additional hour of nursing care per patient day was associated with a 2% decrease in the odds of mortality.

Conclusions:

Our findings suggest that weekend admission was associated with an increase in the odds of mortality in older adults with community-acquired urosepsis. Small increases in nurse staffing seem to reduce the odds of mortality.
Diagnostic Variation in p53 Usage for Endometrial Carcinoma Diagnosis: Implications for Molecular Subtyping
Authors: Baniak Nick , Gilks C. Blake , DeCoteau John , Kinloch Mary
Published: September 2019

Immunostaining for p53 is widely but variably used when diagnosing endometrial carcinoma (EC). Mutant-pattern p53 staining can support a diagnosis of serous carcinoma, and also serve as a surrogate test for identifying the “serous-like” subset of aggressive EC identified by The Cancer Genome Atlas characterized by high numbers of somatic copy number abnormalities. We, retrospectively, assessed WHO histotype, usage of p53 immunostaining, and p53 status in a consecutive series of biopsies showing EC from a single hospital. Of 79 ECs, 59 (75%) were low-grade EC (LGEC), 13 (16%) high-grade EC (HGEC), and 7 (9%) were serous. p53 immunostaining was performed at the time of diagnosis in 27/79 (34%) biopsies; 6/7 of serous histotype, 11/13 HGEC, and 10/59 LGEC. Mutant-pattern p53 staining was present in 6/6 serous, 2/11 HGEC, and 2/10 LGEC. The remaining 53 tumors subsequently had p53 immunostaining done; all 49 LGEC showed wild-type staining and the serous carcinoma and 1/2 HGEC showed mutant pattern staining. While there are no guidelines on using p53 in endometrial biopsies, this study shows consistent usage in high-grade histotypes and variable usage in LGEC. As 100% (7/7) of serous EC and 3% (2/59) of the LGECs showed mutant-pattern p53 staining, histotype may serve as a surrogate for p53 assessment, such that only HGEC or ambiguous carcinomas should be routinely subjected to p53 immunostaining.
Minor Hepatectomies: Focusing a Blurred Picture
Authors: Viganò Luca , Torzilli Guido , Troisi Roberto , Aldrighetti Luca , Ferrero Alessandro , Majno Pietro , Toso Christian , Figueras Joan , Cherqui Daniel , Adam René , Kokudo Norihiro , Hasegawa Kiyoshi , Guglielmi Alfredo , Krawczyk Marek , Giuliante Felice , Hilal Mohammad Abu , Costa-Maia José , Pinna Antonio Daniele , Cescon Matteo , De Santibanes Eduardo , Urbani Lucio , Pawlik Timothy , Costa Guido , Zugna Daniela
Published: September 2019

Objective:

To elucidate minor hepatectomy (MiH) outcomes.

Summary Background Data:

Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures.

Methods:

We retrospectively evaluated consecutive patients who underwent open liver resections in 17 high-volume centers. Exclusion criteria: cirrhosis and associated digestive/biliary resections. Resections were classified as (Brisbane nomenclature): limited resections (LR); (mono)segmentectomies/bisegmentectomies (Segm/Bisegm); right anterior and right posterior sectionectomies (RightAnteriorSect/RightPosteriorSect). Additionally, we defined: complex LRs (ComplexLR = LRs with exposed vessels); postero-superior segmentectomies (PosteroSuperiorSegm = segment (Sg)7, Sg8, and Sg7+Sg8 segmentectomies); and complex core hepatectomies (ComplexCoreHeps = Sg1 segmentectomies and combined resections of Sg4s+Sg8+Sg1). Left lateral sectionectomies (LLSs, n = 442) and right hepatectomies (RHs, n = 1042) were reference standards. Outcomes were adjusted for potential confounders.

Results:

Four thousand four hundred seventy-one MiHs were analyzed. Compared with RHs, MiHs had lower 90-day mortality (0.5%/2.2%), severe morbidity (8.6%/14.4%), and liver failure rates (2.4%/11.6%,P< 0.001), but similar bile leak rates. LR and LLS had similar outcomes. ComplexLR and Segm/Bisegm of anterolateral segments had higher bile leak rates than LLS rates (OR = 2.35 and OR = 3.24), but similar severe morbidity rates. ComplexCoreHeps had higher bile leak rates than RH rates (OR = 1.94); the severe morbidity rate approached that of RH. PosteroSuperiorSegm, RightAnteriorSect, and RightPosteriorSect had severe morbidity and bile leak rates similar to RH rates. MiHs had low liver failure rates, except RightAnteriorSect (vs LLS OR = 4.02).

Conclusions:

MiHs had heterogeneous outcomes. Mortality was low, but MiHs could be stratified according to severe morbidity, bile leak, and liver failure rates. Some MiHs had postoperative outcomes similar to RH.
Vortex motion and geometric function theory: the role of connections
Authors: Gustafsson Björn
Published: September 2019

We formulate the equations for point vortex dynamics on a closed two-dimensional Riemannian manifold in the language of affine and other kinds of connections. This can be viewed as a relaxation of standard approaches, using the Riemannian metric directly, to an approach based more on local coordinates provided with a minimal amount of extra structure. The speed of a vortex is then expressed in terms of the difference between an affine connection derived from the coordinate Robin function and the Levi–Civita connection associated with the Riemannian metric. A Hamiltonian formulation of the same dynamics is also given. The relevant Hamiltonian function consists of two main terms. One of the terms is the well-known quadratic form based on a matrix whose entries are Green and Robin functions, while the other term describes the energy contribution from those circulating flows which are not implicit in the Green functions. One main issue of the paper is a detailed analysis of the somewhat intricate exchanges of energy between these two terms of the Hamiltonian. This analysis confirms the mentioned dynamical equations formulated in terms of connections.

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
Winding of a Brownian particle around a point vortex
Authors: Wen Huanyu , Thiffeault Jean-Luc
Published: September 2019

We derive the asymptotic winding law for a Brownian particle in the plane subjected to a tangential drift due to a point vortex. For winding around a point, the normalized winding angle converges to an inverse Gamma distribution. For winding around a disc, the angle converges to a distribution given by an elliptic theta function. For winding in an annulus, the winding angle is asymptotically Gaussian with a linear drift term. We validate our results with numerical simulations.

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
Vortices and atoms in the Maxwellian era
Authors: Falconer Isobel
Published: September 2019

The mathematical study of vortices began with Herman von Helmholtz's pioneering study in 1858. It was pursued vigorously over the next two decades, largely by British physicists and mathematicians, in two contexts: Maxwell's vortex analogy for the electromagnetic field and William Thomson's (Lord Kelvin) theory that atoms were vortex rings in an all-pervading ether. By the time of Maxwell's death in 1879, the basic laws of vortices in a perfect fluid in three-dimensional Euclidean space had been established, as had their importance to physics. Early vortex studies were embedded in a web of issues spanning the fields we now know as ‘mathematics’ and ‘physics’—fields which had not yet become institutionally distinct disciplines but overlapped. This paper investigates the conceptual issues with ideas of force, matter, and space, that underlay mechanics and led to vortex models being an attractive proposition for British physicists, and how these issues played out in the mathematics of vortices, paying particular attention to problems around continuity. It concludes that while they made valuable contributions to hydrodynamics and the nascent field of topology, the British ultimately failed in their more physical objectives.

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
A vortex ring on a sphere: the case of total vorticity equal to zero
Authors: Boatto Stefanella , Simó Carles
Published: September 2019

The stability of a ring of vortices has attracted the interest of researchers for over a century. Recent beautiful observations of polygonal configurations of vortices present in the atmospheres of Jupiter and Saturn, and of polygonal jets in the Earth's atmosphere, have revived the interest in the subject. In the observed cases, the vortex ring is in the presence of a central vortex. We present analytical and numerical results about the linear, spectral and Lyapunov stability of a ring in the presence of polar vortices. Motivated by both atmospheric observations we considered the special case of total vorticity equal to zero. Such a case has also the very nice property of being
universal
, i.e. not depending on a choice of gauge. We considered the two cases of fixed and non-fixed polar vortices. A ring in the northern (respectively, southern) hemisphere is stabilized by the presence of a northern (respectively, southern) polar vortex of suitable strength, in agreement with what is observed numerically and atmospherically.

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
Euler flows and singular geometric structures
Authors: Cardona Robert , Miranda Eva , Peralta-Salas Daniel
Published: September 2019

Tichler proved (Tischler D. 1970Topology9, 153–154. (doi:10.1016/0040-9383(70)90037-6)) that a manifold admitting a smooth non-vanishing and closed one-form fibres over a circle. More generally, a manifold admittingk-independent closed one-form fibres over a torusTk. In this article, we explain a version of this construction for manifolds with boundary using the techniques ofb-calculus (Melrose R. 1993The Atiyah Patodi Singer index theorem. Research Notes in Mathematics. Wellesley, MA: A. K. Peters; Guillemin V, Miranda E, Pires AR. 2014Adv. Math.(N. Y.)264, 864–896. (doi:10.1016/j.aim.2014.07.032)). We explore new applications of this idea to fluid dynamics and more concretely in the study of stationary solutions of the Euler equations. In the study of Euler flows on manifolds, two dichotomic situations appear. For the first one, in which the Bernoulli function is not constant, we provide a new proof of Arnold's structure theorem and describeb-symplectic structures on some of the singular sets of the Bernoulli function. When the Bernoulli function is constant, a correspondence between contact structures with singularities (Miranda E, Oms C. 2018 Contact structures with singularities.https://arxiv.org/abs/1806.05638) and what we callb-Beltrami fields is established, thus mimicking the classical correspondence between Beltrami fields and contact structures (see for instance Etnyre J, Ghrist R. 2000Trans. Am. Math. Soc.352, 5781–5794. (doi:10.1090/S0002-9947-00-02651-9)). These results provide a new technique to analyse the geometry of steady fluid flows on non-compact manifolds with cylindrical ends.

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
Travel time to health facilities as a marker of geographical accessibility across heterogeneous land coverage in Peru
Authors: Carrasco-Escobar Gabriel , Manrique Edgar , Tello-Lizarraga Kelly , Miranda J. Jaime
Published: September 2019

The geographical accessibility to health facilities is conditioned by the topography and environmental conditions overlapped with different transport facilities between rural and urban areas. To better estimate the travel time to the most proximate health facility infrastructure and determine the differences across heterogeneous land coverage types, this study explored the use of a novel cloud-based geospatial modeling approach and use as a case study the unique geographical and ecological diversity in the Peruvian territory. Geospatial data of 145,134 cities and villages and 8,067 health facilities in Peru were gathered with land coverage types, roads infrastructure, navigable river networks, and digital elevation data to produce high-resolution (30 m) estimates of travel time to the most proximate health facility across the country. This study estimated important variations in travel time between urban and rural settings across the 16 major land coverage types in Peru, that in turn, overlaps with socio-economic profiles of the villages. The median travel time to primary, secondary, and tertiary healthcare facilities was 1.9, 2.3, and 2.2 folds higher in rural than urban settings, respectively. Also, higher travel time values were observed in areas with a high proportion of the population with unsatisfied basic needs. In so doing, this study provides a new methodology to estimate travel time to health facilities as a tool to enhance the understanding and characterization of the profiles of accessibility to health facilities in low- and middle-income countries (LMIC), calling for a service delivery redesign to maximize high quality of care.
Behavior-dependent directional tuning in the human visual-navigation network
Authors: Nau Matthias , Navarro Schröder Tobias , Frey Markus , Doeller Christian F.
Published: September 2019

The brain derives cognitive maps from sensory experience that guide memory formation and behavior. Despite extensive efforts, it still remains unclear how the underlying population activity relates to active behavior and memory performance. To examine these processes, we here combined 7T-fMRI with a kernel-based encoding model of virtual navigation to map world-centered directional tuning across the human cortex. First, we present an in-depth analysis of directional tuning in visual, retrosplenial, parahippocampal and medial temporal cortices. Second, we show that tuning strength, width and topology of this directional code during memory-guided navigation depend on successful encoding of the environment. Finally, we show that participants’ locomotory state influences this tuning in sensory and mnemonic regions such as the hippocampus. We demonstrate a direct link between neural population tuning and human cognition and show that high-level memory processing interacts with network-wide environmental coding in the service of behavior.
Spinal signaling of C-fiber mediated pleasant touch in humans
Authors: Marshall Andrew G. , Sharma Manohar L , Marley Kate , Olausson Hakan , McGlone Francis P.
Published: September 2019

C-tactile afferents form a distinct channel that encodes pleasant tactile stimulation. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways. However, we found that spinothalamic ablation in humans, whilst profoundly impairing pain, temperature and itch, had no effect on pleasant touch perception. Only discriminative touch deficits were seen. These findings preclude privileged C-tactile-lamina I-spinothalamic projections and imply integrated hedonic and discriminative spinal processing from the body.
ZapLine: a simple and effective method to remove power line artifacts
Authors: de Cheveigné Alain
Published: September 2019

Power line artifacts are the bane of animal and human electrophysiology. A number of methods are available to help attenuate or eliminate them, but each has its own set of drawbacks. In this brief note I present a simple method that combines the advantages of spectral and spatial filtering, while minimizing their downsides. This method is applicable to multichannel data such as electroencephalography (EEG), magnetoencephalography (MEG), or multichannel local field potentials (LFP). I briefly review past methods, pointing out their drawbacks, describe the new method, and evaluate the outcome using synthetic and real data.
Peripherally expressed misfolded proteins remotely disrupt brain function and aggravate stroke-induced brain injury
Authors: Liu Yanying , Subedi Kalpana , Baride Aravind , Romanova Svetlana , Huber Christa C. , Wang Xuejun , Wang Hongmin
Published: September 2019

Impaired proteostasis has been linked to various diseases, whereas little is known about the impact of peripherally misfolded proteins on the brain. We here studied the brain of mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryABR120G). At baseline, the CryABR120G mice showed impaired cognitive and motor functions, aberrant protein aggregates, neuroinflammation, impaired blood-brain barrier, and reduced proteasome activity in the brain compared with their non-transgenic (Ntg) littermates. Ischemic stroke dramatically exacerbated these pathological alterations and caused more severe brain dysfunction in CryABR120G mice than in the Ntg mice. Intravenously injecting the exosomes isolated from CryABR120G mouse blood into wild-type mice caused the similar phenotypes seen from CryABR120G mice. Importantly, the CryABR120G protein showed the prion-like properties. These results suggest that peripherally misfolded proteins in the heart remotely disrupt brain function through prion-like neuropathology, which may represent an underappreciated mechanism underlying heart-brain crosstalk.
Crystal structure of β-arrestin 2 in complex with an atypical chemokine receptor phosphopeptide reveals an alternative active conformation
Authors: Min Kyungjin , Yoon Hye-Jin , Park Ji Young , Baidya Mithu , Dwivedi Hemlata , Maharana Jagannath , Chung Ka Young , Shukla Arun K. , Lee Hyung Ho
Published: September 2019

β-arrestins (βarrs) critically regulate signaling and trafficking of G protein-coupled receptors (GPCRs), the largest family of drug targets in the human genome, and there are two isoforms of βarrs: βarr1 and βarr2. Most GPCRs interact with both the heterotrimeric G-proteins and βarrs, inducing distinct downstream signal transduction. However, certain chemokine receptors lack functional G-protein coupling, but they can efficiently recruit βarrs upon agonist-stimulation, and they are referred to as atypical chemokine receptors (ACKRs). Receptor phosphorylation is a key determinant for the binding of βarrs, and understanding the intricate details of receptor-βarr interaction is the next frontier in GPCR structural biology. To date, the high-resolution structures of active βarr1 have been revealed, but the activation mechanism of βarr2 by a phosphorylated GPCR remains elusive. Here, we present a 1.95 Å crystal structure of βarr2 in complex with a phosphopeptide (C7pp) derived from the carboxyl-terminus of ACKR3, also known as CXCR7. The structure of C7pp-bound βarr2 reveals key differences from the previously determined active conformation of βarr1. One of the key differences is that C7pp-bound βarr2 shows a relatively small inter-domain rotation. An antibody-fragment-based conformational sensor and hydrogen/deuterium exchange experiments further corroborate structural features and suggest that the determined structure is an alternative active conformation of βarr2.
Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data
Authors: Sahoo Prativa , Yang Xin , Abler Daniel , Maestrini Davide , Adhikarla Vikram , Frankhouser David , Cho Heyrim , Machuca Vanessa , Wang Dongrui , Barish Michael , Gutova Margarita , Branciamore Sergio , Brown Christine E. , Rockne Russell C.
Published: September 2019

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in the treatment of hematological cancers and is currently being investigated for solid tumors including high-grade glioma brain tumors. There is a desperate need to quantitatively study the factors that contribute to the efficacy of CAR T-cell therapy in solid tumors. In this work we use a mathematical model of predator-prey dynamics to explore the kinetics of CAR T-cell killing in glioma: the Chimeric Antigen Receptor t-cell treatment Response in GliOma (CARRGO) model. The model includes rates of cancer cell proliferation, CAR T-cell killing, CAR T-cell proliferation and exhaustion, and CAR T-cell persistence. We use patient-derived and engineered cancer cell lines with an in vitro real-time cell analyzer to parameterize the CARRGO model. We observe that CAR T-cell dose correlates inversely with the killing rate and correlates directly with the net rate of proliferation and exhaustion. This suggests that at a lower dose of CAR T-cells, individual T-cells kill more cancer cells but become more exhausted as compared to higher doses. Furthermore, the exhaustion rate was observed to increase significantly with tumor growth rate and was dependent on level of antigen expression. The CARRGO model highlights nonlinear dynamics involved in CAR T-cell therapy and provides novel insights into the kinetics of CAR T-cell killing. The model suggests that CAR T-cell treatment may be tailored to individual tumor characteristics including tumor growth rate and antigen level to maximize therapeutic benefit.

Statement of Significance

We utilize a mathematical model to deconvolute the nonlinear contributions of CAR T-cell proliferation and exhaustion to predict therapeutic efficacy and dependence on CAR T-cell dose and target antigen levels.
The First Publicly Available Annotated Genome for Cannabis plants
Authors: Jenkins Conor , Orsburn Ben
Published: September 2019

Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants in North America. We have recently described a pipeline for the creation of annotated protein databases using a combination of genomic and proteomic data and the application of this method toward the analysis of the proteomes of Cannabis plants. In parallel with our work, we approached the National Center for Biotechnology Information (NCBI) to align and annotate publicly deposited genomic files for these plants. In September of 2019, this project was completed. The result, NCBI Cannabis sativa Annotation Release 100 is now live and publicly available. The annotated genome allows, for the first time, the use of classical genetics and proteomics tools for the interrogation of these plants. Furthermore, the presence of an annotated genome within the NCBI Genome browser now permits any researcher with a web browser to manually examine or BLAST genetic sequences, vastly reducing the resources required to create primers to amplify genes from the plants or microbial contaminants that may affect them. We describe this new resource and some points of obvious value to the scientific community as well as the integration into the Cannabis Proteome Draft Map Project.

Significance Statement

Until recently laws in North America have restricted nearly all research on Cannabis plants. Until recent research from our lab, only a few hundred genes and proteins from the plant had been annotated for putative function. The construction of a publicly available annotated genome for this plant allows, for the first time, the use of traditional genomic and proteomic tools for the investigation of these plants. We evaluate herein the first fully annotated publicly available genome for Cannabis plants and the integration of this resource into www.CannabisDraftmap.org