bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary tract infection in infancy and childhood
Authors: Lambert Heather
Published: June 2018

Urinary tract infection (UTI) in childhood is a common problem, which is frequently dismissed as trivial because most children with UTI have a good outcome. However, UTI is an important cause of acute illness in children and causes a considerable burden of ill health on children and families. In addition, UTI may be a marker of an underlying urinary tract abnormality. UTI in a few may cause significant long-term morbidity, renal scarring, hypertension, and renal impairment that may not present until adult life. Predicting which children will go on to have long-term sequelae remains a challenge.

The risk of renal scarring is greatest in infants, the very group in whom diagnosis is often overlooked or delayed because clinical features are non-specific. Delay in treatment is associated with an increased risk of scarring in susceptible children. Thus accurate and rapid diagnosis of UTI is essential and requires a very high index of suspicion particularly in the youngest.

The role of vesicoureteric reflux in acquired scarring is not fully understood though there is clearly an association, possibly because it is a risk factor for acute pyelonephritis. Scarring when it occurs is in the areas affected by acute pyelonephritis. Higher grades of reflux are associated with a worse outcome.

Management and investigation of children with UTI consumes considerable healthcare resources. Limited understanding of the natural history and basic pathophysiology, variations in strategy with time and setting, and lack of evidence on long-term outcomes have resulted in considerable uncertainty. Some propose a minimal approach doing little investigation unless there is clear evidence for it; others favour an approach of continuation of current practice based on clinical experience until further evidence evolves. Some of the themes behind these controversies are explored.
Schistosomiasis
Authors: Barsoum Rashad S.
Published: June 2018

Abstract

Schistosomes are blood flukes that parasitize humans, apes, cattle, and other animals. In these definitive hosts they are bisexual, and lay eggs which are shed to fresh water where they complete an asexual cycle in different snails, ending in the release of cercariae which infect the definitive hosts to complete the life cycle.

Seven of over 100 species of schistosomes are human pathogens, causing disease in different organs depending on the parasite species. Racial and genetic factors are involved in susceptibility, severity, and sequelae of infection.

Morbidity is induced by the host’s immune response to schistosomal antigens. The latter include tegument, microsomal, gut, and oval antigens. The former are important in the process of invasion and establishment of infection, oval antigens in formation of granulomata which lead to fibrosis in different sites, and the gut antigens constitute the main circulating antigens in established infection, leading to immune-complex disease, particularly in the kidneys. The host immunological response includes innate and adaptive mechanisms, the former being the front line responsible for removing 90% of the infecting cercarial load. Adaptive immunity includes a Th1 phase, dominated by activation of an acute inflammatory response, followed by a prolonged Th2 phase which is responsible for immunity to re-infection as well as progression of tissue injury. Switching from Th1 to Th2 phases is controlled by functional and morphological change in the antigen-presenting cells, which is achieved by molecules of host as well as parasitic origin.

Many cells participate in parasite killing, but also in the induction of tissue injury. The most potent of these is the eosinophil, which by binding antibodies to the parasite, particularly immunoglobulin E, facilitates parasite elimination. However, this process is complex, including agonist as well as antagonist pathways, which provide escape mechanisms for the parasite to survive, thereby achieving a delicate balance that permits schistosomes to live for decades in the infected host.
Malaria
Authors: Sakhuja Vinay , Kohli Harbir Singh
Published: June 2018

Of the four pathogenic malarial species, clinically significant renal dysfunction is mainly associated with Plasmodium malariae and Plasmodium falciparum infections.

P. falciparum infection frequently causes acute kidney injury (AKI). AKI may be the sole manifestation with a complete recovery after treatment or it may be a part of multi-organ failure which is often fatal. AKI due to Plasmodium vivax infection alone or as a result of mixed infection by vivax and falciparum can also occur.

‘Quartan malarial nephropathy’ has been attributed to P. malariae infection although this relationship must be regarded as not proven. It describes nephropathy occurring predominantly in children and young adults in Africa. A full-blown nephrotic syndrome is seen in about half the patients and a chronic progressive membranoproliferative glomerulonephritis is usually seen on histology. Spontaneous remission of established nephropathy is rare, and most patients slowly progress to end-stage renal failure over 3 to 5 years even after successful eradication of the infection. The pathological description is such that it could have alternative aetiologies, including other infections.
Hepatitis B
Authors: Muche Marion , Baid-Agrawal Seema
Published: June 2018

Hepatitis B virus (HBV) has been causally linked to a variety of renal diseases, the most common being glomerular diseases and systemic autoimmune disease. Membranous nephropathy (MN) is the commonest HBV-associated glomerulonephritis (HBV-GN), followed by membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis, immunoglobulin (Ig)-A nephropathy, and focal segmental glomerulosclerosis (FSGS). Polyarteritis nodosa is a rare manifestation. The incidence of HBV-associated renal diseases seems to be decreasing with the introduction of vaccination programmes.

HBV-MN is the most frequent cause of nephrotic syndrome in children in countries with high endemicity of HBV infection. The clinical course is usually benign in children with high rates of spontaneous remission rates and low risk of progression to renal failure. The prognosis is worse in adults. Of the systemic autoimmune disorders associated with HBV infection that involve the kidneys, the strongest link has been found with polyarteritis nodosa (PAN), a lesion that causes arteritis of medium-sized renal vessels. HBV-associated PAN (HBV-PAN) usually manifests in the first year after infection, and is clinically indistinguishable from classic PAN.

Diagnosis of HBV-GN or -PAN is based on the clinical picture, histological findings, evidence of viral replication in serum and/or liver and detection of HBV antigens or DNA in the tissue. Besides deposition of immune complexes, other mechanisms such as virus-induced cytopathic damage have been proposed to explain the pathogenesis.

HBV-GN and HBV-PAN appear to respond to antiviral treatment. Both show remission after HBeAg seroconversion. The available studies predominantly employed first-generation agents like interferon alpha and lamivudine, which showed suppression of viral replication and clinical remission of HBV-associated renal disease. Immunosuppressive therapy appears to be inevitable for the control of severe HBV-PAN and could be helpful in addition to antiviral treatment for cases of HBV-GN not responding clinically to antiviral treatment.
Nematode infections
Authors: Ramachandran Raja , Jha Vivekanand
Published: June 2018

In addition to the conditions discussed in other chapters in this section, renal involvement has been described in patients with other infections. These infections are usually encountered in the developing countries, especially of the tropical zone. The tropical environment is conducive to growth of a variety of life forms including infection-causing microorganisms and vectors responsible for disease transmission. Some renal pathology is related to immune responses to the organisms, and false-positive results in some tests of immunity/ autoimmunity may also be seen.

Varieties include lymphatic filariasis, subcutaneous filariasis (including onchocerciasis), and serous filariasis. Lymphatic filariasis can cause milky urine with high levels of (non-glomerular) proteinuria. Four of the 8 nematode pathogenic species have been associated with glomerular disease.
Intermittent acute renal replacement therapy
Authors: Marshall Mark R.
Published: June 2018

This chapter summarizes current best practice with respect to intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for those with acute kidney injury. These modalities can be delivered using a variety of technology platforms. These platforms for the most part use online dialysate, and water quality needs to be monitored and maintained to current standards. Intermittent haemodialysis and SLED provide reasonable outcomes in experienced hands, and ameliorate morbidity and mortality resulting from the ‘acute uraemic syndrome’: that is, intractable infection, non-resolving shock, and haemorrhage.

Careful consideration needs to be given to appropriate modality selection for patients. Lower-efficiency modalities such as continuous therapies or SLED are more appropriate for patients at risk from dialysis disequilibrium syndrome, those with abdominal compartment syndrome, and those who are haemodynamically unstable (including cardiogenic shock). Care should be taken to avoid complications related to rapid fluid and solute removal, anticoagulation, and vascular access. Intradialytic hypotension is detrimental for both general and renal recovery of critically ill patients, and can be mitigated by sodium and ultrafiltration profiling, and frequent treatments and prolonged treatment time to minimize ultrafiltration goals and rates.

Irrespective of the modality applied, an adequate dialysis dose must be achieved. This is facilitated through the use of optimally placed and technically superior central venous catheters, and well-considered prescription of haemodialysis and SLED operating parameters. Dose should be monitored regularly through urea kinetic modelling, either using Kt/V for thrice-weekly schedules or the corrected equivalent renal urea clearance (EKRc) for more frequent ones.
Acute kidney injury in patients with severe burn injury
Authors: Brusselaers Nele , Hoste Eric A. J.
Published: June 2018

Acute kidney injury (AKI) occurs in approximately one-quarter of all patients with severe burn injury (as defined by the RIFLE consensus classification), and approximately 3% of paediatric burn patients. Overall, a three- to six-fold higher mortality for burn patients with AKI is observed, depending on the applied definition. When AKI is defined by the sensitive RIFLE classification, median mortality of AKI is approximately 35%. This chapter describes the general pathophysiology of AKI in burns, particularly the severe form of burn shock, and discusses in addition the roles of intra-abdominal hypertension, rhabdomyolysis, and the potentially negative impact of povidone-iodine burn dressing. Finally the definitions used in burn pathology, the prevention of AKI with a discussion of the fluid therapy in burned patients, and the role of renal replacement therapy in these patients is discussed.
Frequent haemodialysis
Authors: Kliger Alan S. , Suri Rita
Published: June 2018

Haemodialysis is a renal replacement treatment, an ‘artificial kidney’ that performs some of the functions of the normal kidney. It is an inelegant device, providing only a fraction of native kidney’s ability to filter toxins from the blood, but with none of the responsiveness to volume, fine feedback control to regulate solute concentrations, or endocrine functions of the healthy organ. Conventional haemodialysis performed three times a week for 4 hours per treatment filters the blood for only 12 of 168 hours each week, and removes less than 10 per cent of small solutes like urea than does the normal kidney. It is therefore not surprising that haemodialysis patients suffer high morbidity and mortality. A dialysis patient’s expected remaining lifetime is substantially shorter than a comparable person with normal kidney function. For example, a woman aged 40–44 years old in the general population can expect on average 40 more years of life, but if she is on dialysis her life expectancy is only 8.1 years. She is also more likely to have co-morbid disease, including hypertension, cardiovascular disease, metabolic bone disease, anaemia, sepsis, depression, malnutrition and inflammation, and physical and cognitive impairment.
Overview of dialysis patient management and future directions
Authors: Nissenson Allen R. , Moran John , Provenzano Robert
Published: June 2018

Nearly 2 million patients worldwide have end-stage renal disease (ESRD) and require dialysis or kidney transplantation. The advent of clinical dialysis in the 1950s has had a huge impact on the way ESRD and acute kidney injury are managed, but several decades later, the morbidity and mortality in patients with ESRD remain unacceptably high and patients often have a poor quality of life. Many believe that we have focused attention on a few key treatment-related outcomes, and have done well with these (i.e. anaemia, adequacy of dialysis, metabolic bone disease), but achieving great results in only these domains has clearly not been sufficient to drive improvements in survival or patient-reported outcomes. Recent experience with integrated care management, focusing on comorbidity management, offers promise. In addition, a number of investigators have been challenging the current thrice-weekly, diffusion-based treatment paradigm and have been developing approaches to emulate the function of natural kidneys. Thus an ideal care delivery model would focus on the holistic needs of the patient with kidney disease, while the ideal form of renal replacement therapy would mimic native kidneys, operating continuously, removing solutes with a molecular-weight spectrum similar to that of native kidneys, removing water and solutes on the basis of individual patient needs, and would be biocompatible, wearable, and ideally implantable. It would also be low cost, reliable, and safe. A few years ago, these technical requirements would have seemed impossible to achieve, but with advances in the sciences of nanotechnology and microfluidics, renal replacement of the future may come closer to this ideal.
Donor and recipient kidney transplantation surgery
Authors: Allen Richard D. M. , Pleass Henry C. C.
Published: June 2018

Kidney transplant surgery is for thinking surgeons who enjoy being part of a multidisciplinary transplant team. Good ones recognize the small margin for error and avoid difficulties by careful preparation and anticipation of potential pitfalls. Progressively, their role has gained in significance and is now the most important variable in kidney graft loss in the first 6 months after transplantation. Deceased organ donation is complex, expensive, and insufficient in numbers to meet the demand for kidney transplantation. Living donor surgery is therefore a procedure of necessity. Laparoscopic approaches have obvious benefits to the patient but are not operations for the beginner. There are few remaining stalwarts of the open nephrectomy procedure. Because of the limited length of the donor ureter, kidney transplant procedures involve placement of the donor kidney into a heterotopic position with vascular anastomoses to the iliac vessels. No two procedures are the same. Observation of the transplanted kidney changing from a flaccid and pale appearance to one that is firm and pink, and within seconds of removing vascular clamps, is an unforgettable experience for the first timer. Even better is the sight of urine, minutes later. Good transplant centres select their new surgeons carefully!
Infection
Authors: Kotton Camille Nelson
Published: June 2018

The immunosuppression which makes organ transplantation possible increases the risk of infections, both ordinary and opportunistic. The accurate diagnosis and management of infection after organ transplantation reduces morbidity and improves survival. Infections can be acquired in the hospital (i.e. nosocomial infections), from the transplant itself, from the blood product donor, from reactivation of latent infection in the host or from community exposure. Although viral infections are the most common, bacterial, fungal, and parasitic infections are also seen. While the intensity of immunosuppression is at its highest for a year after solid organ transplant, most opportunistic infections occur in the first 6 months.
Pregnancy and renal physiology
Authors: Bramham Kate , Nelson-Piercy Catherine
Published: June 2018

Pregnancy is characterized by unique physiological changes within the kidney, resulting in a marked increase in renal blood flow and glomerular filtration, which are associated with successful pregnancy outcomes. Early in normal pregnancy there are increases in plasma volume and cardiac output, but a lowered peripheral resistance leads to average blood pressures being lower. A pregnancy-associated respiratory alkalosis occurs. Protein excretion tends to increase slightly in women without kidney disease. Kidney size is increased, and pelvicalyceal system dilatation is noticeable in most women in the third trimester, right greater than left.
Ethical aspects of genetic testing
Authors: Flinter Frances
Published: June 2018

The increasing availability of genetic tests is transforming health care. Patients can benefit from earlier, more precise diagnosis and sometimes tailor-made treatment; their relatives can be offered pre-symptomatic, predictive tests and carrier tests. Physicians must balance confidentiality with duty to other individuals, and are responsible for using genetic tests for the benefit of patients in an ethical way. An offer of testing must balance potential additional benefit from potential downsides of testing including psychological effects, risk of error, continuing uncertainty, and cost. The ability to do multiple tests on many genes, even to sequence the whole genome, is rapidly approaching, and mainstreaming of tests means that geneticists are not necessarily involved. Further work and thinking needs to inform medical ethics in this area.
Autosomal dominant polycystic kidney disease
Authors: Ong Albert C. M. , Sandford Richard
Published: June 2018

Based on an estimated population prevalence of between 1 in 400 and 1 in 1000, there are over 60,000 individuals with or at risk of developing complications associated with autosomal dominant polycystic kidney disease (ADPKD) in the United Kingdom. This equates to over 300,000 people in the United States and 7 million worldwide. Once diagnosed, an individual with ADPKD will require long-term medical follow-up and treatment with an unknown cost to national health care systems. A major proportion, probably two-thirds, will develop end-stage renal disease (ESRD) requiring renal replacement therapy—dialysis or transplantation. ADPKD is therefore the commonest genetic cause of ESRD. Most centres worldwide report that approximately one in ten patients receiving dialysis therapy have a diagnosis of ADPKD. Improvements in healthcare for individuals with ADPKD will therefore impact directly on patients, their families, and healthcare resources.
Autosomal dominant polycystic kidney disease
Authors: Ong Albert C. M. , Ellam Timothy
Published: June 2018

Autosomal dominant polycystic kidney disease (ADPKD) is responsible for up to 10% of prevalent patients with end-stage renal disease (ESRD). It is characterized by the enlargement of multiple bilateral renal cysts, present in almost all patients by their fifth decade. Loin pain is a common symptom that may be caused by cyst growth, intracyst haemorrhage, nephrolithiasis, or infection. Gross haematuria is also a common feature, but usually settles spontaneously. Excretory impairment develops after extensive cystic change has occurred and progresses to ESRD in half of all affected patients by the age of 60. However, the onset of cystic change and rate of renal functional decline are highly variable between individuals. ADPKD associated with the PKD1 gene has an earlier average age of cyst development and ESRD than PKD2, but the two cannot be distinguished on clinical grounds. Polycystins 1 and 2 are expressed in various organs and extrarenal disease may be the presenting feature. Intracranial aneurysms are five times more common in patients with ADPKD, but rupture is infrequent. Liver cysts are present in most patients and may be complicated by haemorrhage or infection, though liver failure is very rare. Massive hepatic cystic disease is confined to women, reflecting stimulatory effects of oestrogen on hepatic cyst growth. Cardiovascular disease is the leading cause of death in ADPKD and vascular dysfunction is present in many patients even before the development of excretory impairment. However, despite the multisystem manifestations of ADPKD, survival from ESRD is better for patients with ADPKD than for other non-diabetic causes of kidney failure.
Nephronophthisis
Authors: Sayer John A. , Simms Roslyn J.
Published: June 2018

Nephronophthisis (NPHP) is a clinically heterogeneous autosomal recessive cystic kidney disease and the leading genetic cause of end-stage renal failure in children and young adults. Whilst enlarged dysplastic cystic kidneys are associated with infantile NPHP, more typically renal ultrasound reveals normal kidney size and corticomedullary cysts in a child with polyuria and secondary enuresis. Extrarenal manifestations occur in 10–15% including retinal degeneration, cerebellar vermis hypoplasia and liver fibrosis, requiring referral to other specialists. Mutations in 18 genes have been identified to cause NPHP, but a genetic diagnosis still cannot be found in many patients. NPHP is classified as a ciliopathy because of the localization of the protein products of the associated genes. Currently there is no specific therapy for NPHP.
Fabry disease
Authors: Waldek Stephen
Published: June 2018

Fabry disease is a rare X-linked lysosomal storage disorder in which deficiency of alpha-galactosidase A leads to accumulation of substrate, mostly globotriaosylceramide (Gb3), which causes a progressive, multiorgan disease affecting predominantly the kidneys, skin, heart, and nervous system. Painful peripheral (‘acral’) neuropathy is characteristic. Proteinuria and estimated glomerular filtration rate (eGFR) are strongly associated with risk of progression, but this may be reduced by treatment with angiotensin-converting enzyme inhibitors as well as by enzyme replacement therapy (ERT). ERT was approved in 2001; it improves pain and other neuropathic symptoms, and well-being, and has been proven to clear deposits of Gb3 from tissues, at variable speeds. There is limited randomized controlled trial data but protective effects have been proven for renal outcomes, death, and better outcomes in some other organ systems. Renal function may be protected if ERT is commenced before there is heavy proteinuria or substantial loss of GFR. It is recommended to start ERT as soon as the diagnosis is made in those with very low or absent enzyme. For those with intermediate levels it is recommended to commence treatment only when signs or symptoms appear. Proteinuria and eGFR give most information from a renal point of view, but renal biopsy is also useful for confirming the renal diagnosis and staging the disease as well as monitoring progress in selected cases. Management should include regular screening for complications including myocardial and neurological assessments. It is likely that registries will show progressive rises in median survival with this condition.
APOL1 and renal disease
Authors: Turner Neil , Tandon Teena , Agarwal Rajiv
Published: June 2018

Although apolipoprotein L1 (APOL1) is not known to be a direct cause of renal disease, it has emerged as a powerful cofactor in several important conditions. APOL1 gene polymorphisms account for the restriction of HIV-associated collapsing focal segmental glomerulosclerosis (FSGS) to those with African ancestry. In Africa, the disease-predisposing alleles seem to have been selected for because they convey resistance to some strains of trypanosomiasis. The same alleles are associated with increased susceptibility to primary FSGS, and are probably able to fully account for the excess of FSGS in black races. Two high-risk alleles have been labelled G1 and G2. To have increased susceptibility, individuals must usually have two copies, that is, it is recessive, but the gene frequency is high in West and Southern Africa and in those descended from those regions. The same alleles convey susceptibility to other more common renal diseases. Numerically the most significant association is with nephropathy previously attributed to hypertension. Recent evidence suggests that the gene may increase rate of progression in renal disease of various types, including diabetes. The mechanism is not known.
MYH9 and renal disease
Authors: Turner Neil , Knebelmann Bertrand
Published: June 2018

MYH9 encodes one of three heavy chain isoforms for the non-muscle myosin II (NM II) molecule. NM II is involved in cell structure and shape and motility. Myosin II is very widely expressed but MYH9 is highly expressed in podocytes. MYH9 diseases are characterized by various combinations of autosomal dominant progressive, proteinuric renal disease, giant platelets with low platelet counts, progressive sensorineural hearing impairment, granulocyte inclusions, and in some patients also cataracts. Although the eponyms Epstein and Fechtner have been given to MYH9 renal syndromes, there is a spectrum of manifestations of MYH9 diseases that do not correlate perfectly with genotype. They are best described as MYH9-associated renal disease. The occurrence of progressive deafness and renal failure led to this condition being considered an Alport syndrome variant in the past, but phenotype as well as molecular genetics clearly separate the disorders.
Primary vesicoureteric reflux and reflux nephropathy
Authors: Lambert Heather
Published: June 2018

Vesicoureteric reflux (VUR) describes the flow of urine from the bladder into the upper urinary tract when the ureterovesical junction fails to perform as a one-way valve. Most commonly, VUR is primary, though it can be secondary to bladder outflow obstruction and can occur in several multiorgan congenital disorders. There is good evidence of a genetic basis with a greatly increased risk of VUR in children with a family history of VUR. VUR is a congenital disorder, which largely shows improvement or complete resolution with age. Fetal VUR may be associated with parenchymal developmental defects (dysplasia). Postnatally non-infected, non-obstructed VUR does not appear to have a detrimental effect on the kidneys. However there is an association of VUR with urinary tract infection and acquired renal parenchymal defects (scarring). The parenchymal abnormalities detected on imaging, often termed reflux nephropathy, may be as a result of reflux-associated dysplasia or acquired renal scarring or both. It is difficult to distinguish between the two on routine imaging. Higher grades of VUR are associated with more severe reflux nephropathy. The precise role of VUR in pyelonephritis and scarring is not clear and it may be that VUR simply increases the risk of acute pyelonephritis. Whilst most VUR resolves during childhood, it is associated with an increased risk of urinary tract infection and burden of acute disease. Investigation strategies vary considerably, related to uncertainties about the natural history of the condition and the effectiveness of various interventions. The long-term prognosis is chiefly related to the morbidity of reflux nephropathy leading in some cases to impairment of glomerular filtration rate, hypertension, proteinuria, and pregnancy-related conditions including hypertension, pre-eclampsia, and recurrent urinary tract infection. Management is controversial and ranges from simple observation with or without provision of rapid access to diagnosis and treatment of urinary tract infections; to long-term prophylactic antibiotics or various antireflux surgical procedures.
A global curriculum for training the next generation of nephrologists
Authors: Vachharajani Tushar J. , Phoon Richard K. S. , Harris David C. H.
Published: June 2018

A nephrologist should have the generic skills of a consultant general physician, plus theoretical knowledge, and skills in nephrology.
Moving on from a purely apprenticeship model, in the last 40 years several countries have listed the desirable knowledge and skills content for a specialist nephrologist in their jurisdiction. Some of these lists are exhaustive. Assessments of competence often include a written test of knowledge, and workplace based assessment or reports on specific skills or overall performance.
We list some of the common generic headings used to define these areas of competence, and point to some curricula for specialist nephrologists. We also summarize methods of learning and point to resources which are available internationally, particularly online.
The majority of the numerical need for additional nephrologists globally is in regions with fewer physicians, and fewer resources for their education. The ISN has proposed a global curriculum and identified how this might be tailored to regional needs. We might all help with producing support learning internationally, and we point to some good sources below.

How to best support the development of nephrologists in these regions without unintentionally attracting them away from places of greatest need is an important question.
Alternative Hosts for Soybean vein necrosis virus and Feeding Preferences of Its Vector Soybean Thrips
Authors: Irizarry Melissa D. , Elmore Manjula G. , Batzer Jean C. , Whitham Steven A. , Mueller Daren S.
Published: June 2018

Soybean vein necrosis virus (SVNV), a tospovirus and one of the most widespread soybean viruses in North America, is primarily transmitted by soybean thrips (Neohydatothrips variabilis). Although soybean is not considered the primary plant host for SVNV, there is a dearth of knowledge about alternative host plants for SVNV. We therefore investigated whether commonly present specialty and cover crops in Iowa can serve as alternative hosts for SVNV. Seventeen cover crops and seven specialty crops were tested using mechanical and thrips inoculations. Clear symptoms of SVNV and systemic infection in buckwheat and clear local infection with possible systemic infection on melon were shown. Additionally, we compared soybean thrips feeding on 18 cover crops and determined that they preferred alfalfa, buckwheat, crimson clover, and red clover. Our results suggested that alternative host crops may harbor SVNV and be a possible source of inoculum for soybean.
Functional Data Analysis of Weather Variables Linked to Fusarium Head Blight Epidemics in the United States
Authors: Shah D. A. , De Wolf E. D. , Paul P. A. , Madden L. V.
Published: June 2018

In past efforts, input weather variables for Fusarium head blight (FHB) prediction models in the United States were identified after following some version of the window-pane algorithm, which discretizes a continuous weather time series into fixed-length windows before searching for summary variables associated with FHB risk. Functional data analysis, on the other hand, reconstructs the assumed continuous process (represented by a series of recorded weather data) by using smoothing functions, and is an alternative way of working with time series data with respect to FHB risk. Our objective was to functionally model weather-based time series data linked to 865 observations of FHB (covering 16 states and 31 years in total), classified as epidemics (FHB disease index ≥ 10%) and nonepidemics (FHB disease index < 10%). Altogether, 94 different time series variables were modeled by penalized cubic B-splines for the smoothing function, from 120 days pre-anthesis to 20 days post-anthesis. Functional mean curves, standard deviations, and first derivatives were plotted for FHB epidemics relative to nonepidemics. Function-on-scalar regressions assessed the temporal trends of the magnitude and significance of the mean difference between functionally represented weather time series associated with FHB epidemics and nonepidemics. The mean functional weather-variable curve for epidemics started to deviate, in general, from that for nonepidemics as early as 40 days pre-anthesis for several weather variables. The greatest deviations were often near anthesis, the period of maximum susceptibility of wheat to FHB-causing fungi. The most consistent separations between the mean functional curves were seen with the daily averages of moisture-related variables (such as average relative humidity) and with variables summarizing the daily variation in temperature (as opposed to the daily mean). Functional data analysis was useful for extending our knowledge of relationships between weather variables and FHB epidemics.
Phenotypes of Thyroid Eye Disease
Authors: Uddin Jimmy M. , Rubinstein Tal , Hamed-Azzam Shirin
Published: June 2018

Purpose:

To describe a new classification system of thyroid eye disease (TED) based on the phenotypic features (clinical and radiologic) of the disease.

Methods:

Clinical features, photographic, and orbital imaging of TED patients were considered in relation to their natural history and treatment response in the experience of the author. Phenotypically distinct categories of patients were identified and described.

Results:

Six phenotypes of TED are observed: 1) congestive (active inflammatory), 2) “white eye” expansion, 3) “hydraulic” apex, 4) “white eye” apex, 5) cicatricial active, and 6) cicatricial passive.

Conclusions:

The observable characteristics of TED are determined by the underlying pathophysiology of the disease. TED is heterogeneous in its underlying pathogenesis, clinical manifestations, and response to medical and surgical treatment modalities. Several previous categorizations of the clinical appearance of TED exist, but they are dichotomous and underrepresent the heterogeneity of the disease. The authors present clinical and radiologic features of 6 different classes or phenotypes of TED and their response to different treatments.
Screening for depression: Review of the Patient Health Questionnaire-9 for nurse practitioners
Authors: O'Byrne Patrick , Jacob Jean Daniel
Published: June 2018

Background and purpose:

Depression is a major health concern encountered by nurse practitioners working in an array of health care settings. Many current guidelines and articles on this topic recommend using the Patient Health Questionnaire-9 (PHQ-9) as a screening tool. Nurse practitioners should have a sophisticated knowledge of this tool.

Methods:

Review of the criteria for diagnosing depression as well as depression screening tools. Database search of EMBASE, CINAHL, and MEDLINE for articles about the PHQ-9. Discussion of how the instrument is used in the clinical setting.

Conclusions:

The PHQ-9 is a free tool that nurse practitioners can use to screen patients in the primary care environment. Screening will detect more instances of depression, which is often missed in this population of patients.

Implications for practice:

Nurse practitioners can and should use the PHQ-9 when screening for depression. However, they should do so with full knowledge and awareness of its strengths and limitations.
Insular biogeographic origins and high phylogenetic distinctiveness for a recently depleted lizard fauna from Christmas Island, Australia
Authors: Oliver Paul M. , Blom Mozes P. K. , Cogger Harold G. , Fisher Robert N. , Richmond Jonathan Q. , Woinarski John C. Z.
Published: June 2018

Striking faunal turnover across Asia and Australasia, most famously along the eastern edge of the Sunda Shelf or ‘Wallace's Line’, has been a focus of biogeographic research for over 150 years. Here, we investigate the origins of a highly threatened endemic lizard fauna (four species) on Christmas Island. Despite occurring less 350 km south of the Sunda Shelf, this fauna mostly comprises species from clades centred on the more distant regions of Wallacea, the Pacific and Australia (more than 1000 km east). The three most divergent lineages show Miocene (approx. 23–5 Ma) divergences from sampled relatives; and have recently become extinct or extinct in the wild, likely owing to the recent introduction of a southeast Asian snake (
Lycodon capucinus
). Insular distributions, deep phylogenetic divergence and recent decline suggest that rather than dispersal ability or recent origins, environmental and biotic barriers have impeded these lineages from diversifying on the continental Sunda Shelf, and thereby, reinforced faunal differentiation across Wallace's Line. Our new phylogenetically informed perspective further highlights the rapid loss of ancient lineages that has occurred on Christmas Island, and underlines how the evolutionary divergence and vulnerability of many island-associated lineages may continue to be underestimated.
LncRNA Spehd regulates hematopoietic stem cells and progenitors and is required for multilineage differentiation
Authors: Joaquina Delás M , Jackson Benjamin T , Kovacevic Tatjana , Vangelisti Silvia , Maravilla Ester Munera , Wild Sophia A , Stork Eva Maria , Erard Nicolas , Knott Simon RV , Hannon Gregory J
Published: June 2018

Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell-type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs might play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Our studies identified two lncRNAs that were required for hematopoiesis. One of these, Spehd, showed defective multi-lineage differentiation, and its silencing yielded common myeloid progenitors deficient in their oxidative phosphorylation pathway. This effort not only suggests that lncRNAs can contribute to differentiation decisions during hematopoiesis but also provides a path toward the identification of functional lncRNAs in other differentiation hierarchies.
Inductance in Neural Systems
Authors: Wang Hao , Wang Jiahui , Yuan Thow Xin , Lee Sanghoon , Xian Peh Wendy Yen , Ann Ng Kian , He Tianyiyi , Thakor Nitish V. , Chen Chia-Hung , Lee Chengkuo
Published: June 2018

A neural circuit model involving inductance is established to explain the neural networks’ behavior. A parallel resistor-inductor-capacitor (RLC) circuit was used to fit the stimulus artifacts in the electromyography (EMG) recording of cortical and pelvic electrical nerve stimulations. This parallel RLC circuit model also predicts the resonance effect in both stimulus artifacts and EMG signals. Moreover, the well-known strength-duration relationship was directly derived to be a precise format with this parallel RLC circuit model. A theoretical explanation is provided to show the inductance is generated by the coil structure of the myelin sheath and the piezoelectric effect of the plasma membrane.

One Sentence Summary:

The inductance in the neural systems is generated by the coil structure of the myelin sheath and the piezoelectric effect of the plasma membrane.
Robust and conserved stochastic self-assembly mechanism for dynamic ParB-parSpartition complexes on bacterial chromosomes and plasmids
Authors: Diaz Roxanne , Sanchez Aurore , Rech Jérôme , Labourdette Delphine , Dorignac Jérôme , Geniet Frédéric , Palmeri John , Parmeggiani Andrea , Boudsocq François , Leberre Véronique Anton , Walter Jean-Charles , Bouet Jean-Yves
Published: June 2018

Chromosome and plasmid segregation in bacteria are mostly driven by ParABS systems. These DNA partitioning machineries rely on large nucleoprotein complexes assembled on centromere sites (parS). However, the mechanism of how a fewparS-bound ParB proteins nucleate the formation of highly concentrated ParB clusters remains unclear despite several proposed physico-mathematical models. We discriminated between these different models by varying some key parametersin vivousing the plasmid F partition system. We found that ‘Nucleation & caging’ is the only coherent model recapitulatingin vivodata. We also showed that the stochastic self-assembly of partition complexes (i) does not directly involve ParA, (ii) results in a dynamic structure of discrete size independent of ParB concentration, and (iii) is not perturbed by active transcription but is by protein complexes. We refined the ‘Nucleation & Caging’ model and successfully applied it to the chromosomally-encoded Par system ofVibrio cholerae, indicating that this stochastic self-assembly mechanism is widely conserved from plasmids to chromosomes.
Optimally designed vs intuition-driven inputs: the study case of promoter activity modelling
Authors: Bandiera L. , Kothamachu V. , Balsa-Canto E. , Swain P. S. , Menolascina F.
Published: June 2018

Synthetic biology is an emerging engineering discipline that aims at synthesising logical circuits into cells to accomplish new functions. Despite a thriving community and some notable successes, the basic task of assembling predictable gene circuits is still a key challenge. Mathematical models are uniquely suited to help solve this issue. Yet in biology they are perceived as expensive and laborious to obtain because low-information experiments have often been used to infer model parameters. How much additional information can be gained using optimally designed experiments? To tackle this question we consider a building block in Synthetic Biology, an inducible promoter in yeast S. cerevisiae. Using in vivo data we re-fit a mathematical model for such a system; we then compare in silico the quality of the parameter estimates when model calibration is done using typical (e.g. step inputs) and optimally designed experiments. We find that Optimal Experimental Design leads to ~70% improvement in the predictive ability of the inferred models. We conclude providing suggestions on how optimally designed experiments can be implemented in vivo.
Structural evolutionary analysis predicts functional sites in the artemisinin resistance malaria protein K13
Authors: Coppée Romain , Jeffares Daniel C. , Sabbagh Audrey , Clain Jérôme
Published: June 2018

K13 is an essential Plasmodium falciparum protein that plays a key role in malaria resistance to artemisinins. Although K13 resembles BTB- and Kelch/propeller-containing proteins involved in ubiquitin ligase complexes, its functional sites remain uncharacterized. Using evolutionary and structural information, we searched for the most conserved K13 sites across Apicomplexa species evolution to identify sub-regions of K13 that are likely functional. An amino acid electropositive ‘patch’ in the K13 propeller domain has a dense concentration of extraordinarily conserved positions located at a shallow pocket, suggesting a role as binding surface. When applied to experimentally-characterized BTB-Kelch proteins, our strategy successfully identifies the validated substrate-binding residues within their own propeller shallow pocket. Another patch of slowly evolving sites is identified in the K13 BTB domain which partially overlaps the surface that binds to Cullin proteins in BTB-Cullin complexes. We provide candidate binding sites in K13 propeller and BTB domains for functional follow-up studies.
Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures
Authors: Nadig Ajay , Reardon Paul K. , Seidlitz Jakob , McDermott Cassidy L. , Blumenthal Jonathan D. , Clasen Liv S. , Lalonde Francois , Lerch Jason P. , Chakravarty Mallar M. , Raznahan Armin
Published: June 2018

Sex chromosome aneuploidy (SCA) enhances risk for several psychiatric disorders associated with the limbic system, including mood and autism spectrum disorders. These patients provide a powerful genetics-first model for understanding the biological basis of psychopathology. Additionally, these disorders are frequently sex-biased in prevalence, further suggesting an etiological role for sex chromosomes. To clarify how limbic anatomy varies across sex and sex chromosome complement, we characterized amygdala and hippocampus structure in a uniquely large sample of patients carrying supernumerary sex chromosomes (n = 132) and typically developing controls (n=166). After correction for sex-differences in brain size, karyotypically normal males (XY) and females (XX) did not differ in volume or shape of either structure. In contrast, all SCAs were associated with lowered amygdala volume relative to gonadally-matched controls. This effect was robust to three different methods for total brain volume correction, including an allometric analysis that derived normative scaling rules for these structures in a separate, typically developing population (n = 79). Hippocampal volume was insensitive to SCA after correction for total brain volume. However, surface-based analysis revealed that SCA, regardless of specific karyotype, was consistently associated with a spatially specific pattern of shape change in both amygdala and hippocampus. In particular, SCA was accompanied by contraction around the basomedial nucleus of the amygdala and an area within the hippocampal surface that cuts across hippocampal subfields. These results demonstrate the power of SCA as a model to understand how copy number variation can precipitate changes in brain systems relevant to psychiatric disease.
A multilevel statistical toolkit to study animal social networks: Animal Network Toolkit (ANT) R package
Authors: Sebastian Sosa , Ivan Puga-Gonzalez , He Hu Feng , Peng Zhang , Xie Xiaohua , Cédric Sueur
Published: June 2018

How animals interact and develop social relationships regarding, individual attributes, sociodemographic and ecological pressures is of great interest. New methodologies, in particular Social Network Analysis, allow us to elucidate these types of questions. However, the different methodologies developed to that end and the speed at which they emerge make their use difficult. Moreover, the lack of communication between the different software developed to provide an answer to the same/different research questions is a source of confusion. The R package Animal Network Toolkit (ANT) was developed with the aim of implementing in one package the many different social network analysis techniques currently used in the study of animal social networks. Hence, ANT is a toolkit for animal research allowing among other things to: 1) measure global, dyadic and nodal networks metrics; 2) perform data randomization: pre-network and network (node and link) permutations; 3) perform statistical permutation tests. The package is partially coded in C++ for an optimal coding speed, and it gives researchers a workflow from raw data to the achievement of statistical analyses, allowing for a multilevel approach: from individual position and role within the network, to the identification of interaction patterns, and the analysis of the overall network properties.