Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4,000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.

Food allergy is a major public health issue with growing prevalence in the urbanized world and significant impact on the lives of allergic patients and their families. Research into the risk factors that have contributed to this increase and their underlying immune mechanisms could lead us to definitive ways for treatment and prevention of food allergy. For the time being, introduction of peanut and other allergenic foods in the diet at the time of weaning seems to be an effective way to prevent the development of food allergy. Improved diagnosis and appropriate management and support of food allergic patients are central to patient care with food immunotherapy and biologicals making the transition to clinical practice. With the new available treatments it is becoming increasingly important to include patient's and family preferences to provide a management plan tailored to their needs.

Introduction. Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) WNT subtype as well, the course of which has only recently been described. Methods. We retrospectively retrieved all patients with documented germline APC mutations and a centrally-reviewed diagnosis of MBL to examine the outcome of their MBL, late effects of its treatment, and further oncological events. Results. Between 2007-2016 we diagnosed and treated 6 patients, all with a pathogenic APC variant mutation, who all had MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine and vincristine for a maximum of 8 courses. Five of 6 diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Four of 6 patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other 2 cases. Four patients had developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. Discussion. Our data confirm a good prognosis for patients with MBL associated with FAP. Patients’ secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

Background: Sickle cell disease (SCD) is a genetic blood disorder that results in vaso-occlusive events and shortened lifespan. Medical advancements have led to a decrease in childhood mortality in SCD, but the transition period is associated with poor outcomes. We analyzed recent US hospitalizations and mortality trends in the transition-aged population and evaluated for differences between patients with and without SCD. Methods: Nationwide Impatient Sample (NIS) database was utilized to analyze hospitalizations among individuals aged 16-24 years from 2003-2017. Diagnoses were coded using ICD-9-CM and ICD-10-CM. Statistical analyses included: bivariate analyses to assess the association between socio-demographic characteristics, joinpoint regression analysis to describe trends in mortality rates, average annual percent change (AAPC) measures were calculated, and adjusted survey logistic regression to assess the association between patient characteristics and in-hospital mortality. Results: Our data captured 37,344,532 total patients between the age of 16 and 24 who were hospitalized during 2003-2017. Patients with SCD comprised of 1.20% of population with a significant +3.2% AAPC in hospitalizations. When comparing SCD to non-SCD hospitalization trends, we observed differences in gender, against-medical-advice discharge status, zip code income, and payer. SCD in-hospital mortality rates showed a non-significant -0.7% AAPC. However, in contrast to non-SCD patients, the odds ratios for in-hospital mortality significantly increased with age for SCD patients. Conclusion: During the transition period, SCD patients have an extremely increased likelihood of mortality. Proposed interventions to address this disparity must include targeting social determinants of health.

High-grade gliomas (HGGs) are a challenging group of brain tumors. Identification of targetable genetic alterations such as TRK fusions are providing new treatment options. We discuss an infant who presented with hydrocephalus and a cystic mass at birth, while a solid tumor component of the mass was only appreciated later. Tumor analysis was consistent with HGG containing a TRK fusion. Despite treatment with conventional chemotherapy, his tumor progressed in size. He was started on larotrectinib and experienced a significant decrease in tumor burden. This case demonstrates that targeted therapy may be effective for a subset of TRK fusion-positive CNS tumors.

NTRODUCCIONEl tumor odontogénico adenomatoide (TOA), según la OMS, es una lesión epitelial tumoral benigna de origen odontogénico, de crecimiento lento. Es considerado como infrecuente; tiende a presentarse con mayor frecuencia en la zona anterior del maxilar, asociado a un diente retenido (más frecuentemente el canino), y con cierta predilección por el sexo femenino. Presenta tres variantes clínicas: folicular, extrafolicular y periférica.Es más frecuente antes de la tercera década de la vida aunque se han reportado casos entre los 3 y los 28 años, con un promedio de edad de 13,2 años. Representa el 3% de todos los tumores odontogénicos. un tumor pequeño de no más de 3 cm. .Lo que todavía continúa cuestionandose es que el TOA es una entidad muy variable, de la cual no ha sido posible precisar si es una neoplasia o un hamartoma.Palabras claves: Hamartoma, neoplasia, deinte retenido, quiste, tumor, etc.

Abstract Objetives: Currently, there is scarce evidence about protocols and algorithms for making decisions to support the decannulation process of pediatric patients. The aim of the present study is to make a systematic review of decannulation protocols in pediatric patients that are available in the published literature. Methods: Systematic review of relevant published literature until January 2020 based on studies where a decannulation algorithm or protocol was applied to 1 to 18 year-old pediatric patients who suffered tracheostomy. Main outcomes were Successful decannulation and length of hospital stay. Results: Twenty two studies were included in the review. All the studies were descriptive. Reason for tracheostomy was reported in 76% of the studies most being because of upper airway and facial disorders. Decannulation protocols or algorithms were used in all studies with the exception of one. The successful decannulation rate was over 70% in most studies. Vital signs monitoring as well as partial oxygen saturation were the most used variables in most of cases to decide on decannulation. Conclusion: The lack of proven variabilities which can be used during the decannulation process makes it difficult to provide specific recommendations for decannulation protocols. More level II studies are needed in order to evaluate its effectiveness. There is no consensus amongst the authors regarding the use of the test of occlusion on the tracheostomy cannula, but they agree that polysomnography is a complementary method to fibroscopy which may be related to decannulation success prediction.

Version of record in Molecular Ecology Resources:  https://doi.org/10.1111/1755-0998.13402 The Maroni is one of the most speciose basins of the Guianas and hosts a megadiverse freshwater fish community. Although taxonomical references exist for both the Surinamese and Guyanese parts of the basin, these lists were mainly based on morphological identification and there are still taxonomical uncertainties concerning the status of several fish species. Here we present a barcode dataset of 1,284 COI sequences from 199 freshwater fish species (68.86% of the total number of strictly freshwater fishes from the basin) from 124 genera, 36 families, and 8 orders. DNA barcoding allowed for fast and efficient identification of all specimens studied as well as unveiling a consequent cryptic diversity, with the detection of 20 putative cryptic species and 5 species flagged for re-identification. In order to explore global genetic patterns across the basin, genetic divergence landscapes were computed for 128 species, showing a global trend of high genetic divergence between the Surinamese south-west (Tapanahony and Paloemeu), the Guianese south-east (Marouini, Litany, Tampok, Lawa…), and the river mouth in the north. This could be explained either by lower levels of connectivity between these three main parts or by the exchange of individuals with the surrounding basins. A new method of ordination of genetic landscapes successfully assigned species into cluster groups based on their respective pattern of genetic divergence across the Maroni Basin: genetically homogenous species across the basin were effectively discriminated from species showing high spatial genetic fragmentation and possible lower capacity for dispersal.

The understanding of the dynamics of stomatal movements has increased substantially through genetic manipulation of plant metabolism either at the whole plant level or specifically in guard cells. However, the regulation of stomatal speediness remains not completely elucidated. Here we shown that reduced expression of guard cell sucrose synthase 2 (NtSUS2) of Nicotiana tabacum L. altered the topology and the connectivity of the guard cell metabolic network and the accumulation of metabolites positively correlated with stomatal speediness during dark-to-light transition. This leads to a slower light-induced stomatal opening, lower steady-state stomatal conductance and a strong reduction (up to 44%) in daily whole plant transpiration in the transgenics, when compared to wild type plants. Furthermore, the transgenic lines transpired more or have lower reduction in whole plant transpiration under short water deficit periods, indicating a higher effective use of water under this condition. Our results collectively suggest that the regulation of stomatal movement and speediness involve a complex modulation of the guard cell metabolic network, in which NtSUS2 has an important role. The results are discussed on the role of guard cell metabolism for the regulation of both stomatal speediness and whole plant transpiration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and 2019 novel coronavirus (2019-nCoV) pose a serious threat to human health. To determine the genetic relationships between the two clades and the genetic mechanism of origin of 2019-nCoV, we compared the whole genomic sequences of SARS-CoV and 2019-nCoV and dissected their phylogenetic histories. Surprisingly, we found that the two clades have frequently exchanged genetic material through homologous recombination in recent decades. Nearly 2/3 of the genetic material of CoVZC45 comes from 2019-nCoV lineage, while the other 1/3 descends from SARS-CoV clade. In particular, the 2019-nCoV lineage might have acquired its receptor-binding domain from the SARS-CoV clade, enabling 2019-nCoV to bind to human angiotensin-converting enzyme 2 receptor and helping it to spread rapidly in humans. Our findings suggest the role of a virus of the SARS-CoV clade in causing COVID-19 and warn of the possible emergence of more mosaic CoVs capable of causing severe epidemics.

Objectives: The aims of the study were to further elucidate the roles of M1 and M2 macrophages in the pathogenesis of EAE and the effects of treatment with M2 macrophages that target certain pro-inflammatory cytokines and with immunomodulatory preparations that beneficially influence the disease course should be in focus of future therapeutic trials. Results: Enhanced the total number of macrophages at the onset of clinical signs in the EAE group, consistent with an increased proportion of M1 cells and low numbers of M2 cells. As the disease progressed and the symptoms worsened, M1 cells were decreased and M2 cells were gradually increased till the peak. In the recovery stage, M2 cell numbers were gradually decreased. Treatment with M2 macrophages inhibited the NF-κb pathway, alleviated the symptoms of EAE, reduced inflammatory cell infiltration and demyelination in the central nervous system, and decreased the numbers of macrophages in the spleens. BAY-11-7082, an NF-κb blocking agent, could reduce the total number of macrophages both in vivo and in vitro, effectively prevented the EAE development, and significantly inhibited the symptoms EAE in mice. Conclusions: Macrophages may play a crucial role in the pathogenesis of EAE, while M2 macrophages have anti-inflammatory effects. Transfer of M2 macrophages to EAE mice can block the NF-κb pathway successfully and relieve the EAE symptoms. Application of NF-κb blockers is useful in the prevention and treatment of EAE.

Introduction: Intranasal steroid injections were once routinely performed for refractory allergy patients worldwide. Due to concerns about visual complications, the procedure is very rarely performed today. Nonetheless, many studies evaluating the technique advocate for its use. Methods: A narrative review of the history of intranasal steroid injections was performed. Additionally, the analogous experiences of non-otolaryngology providers with steroid injection treatments were assessed. Results: Many non-otolaryngology providers have had similar, devastating thromboembolic complications from particulate steroid injections. In other fields, a switch to non-particulate steroid formulations (e.g. dexamethasone) appears to avoid the risk of thromboembolic events entirely without sacrificing effectiveness. Conclusion: The otolaryngologists’ aversion to intranasal injection treatments may not be evidence-based. Intranasal injection treatments with non-particulate steroids as well as other medications merit consideration.

Introduction; This review discusses how nasal congestion may have benefits as a mechanism of defence against respiratory viruses. Methods; A literature research was conducted on respiratory viruses and nasal congestion, following a recently published review on how temperature sensitivity is important for the success of common respiratory viruses. Results; The literature reported that common respiratory viruses are temperature sensitive and replicate well at the cooler temperatures of the upper airways (32oC), but replication is restricted at body temperature (37oC). The amplitude of the phases of congestion and decongestion associated with the nasal cycle was increased on infection with respiratory viruses and this caused unilateral nasal congestion and obstruction. Nasal congestion and obstruction increase nasal mucosal temperature towards 37oC and therefore restricted the replication of respiratory viruses. Conclusion; Nasal congestion associated with the nasal cycle may act as a mechanism of respiratory defence against infection with respiratory viruses

The American obstetrician, Joseph DeLee, ‘father of modern obstetrics’, founded the Chicago Lying-in Hospital in 1931 with his vision for womens’ health captured in a set of five stone plaques at the top of the cloister of the hospital’s building. Four of the five stone plaques are engraved with the names of pioneering clinicians whose contributions to the field of obstetrics and gynaecology have been seminal: Jan Palfyn (1650-1730), for introducing the obstetric forceps in the 1720s, Hendrik Van Deventer (1651-1724), for discovering obstetric anatomical disorders, William Smellie (1697-1763), for improving the design of the forceps, and Eduardo Porro (1842 –1902), for introducing hysterectomy to stop postpartum haemorrhage. The fifth stone plaque, in the centre, which is still blank today, is reserved for the physician/scientist who discovers the cause and cure of preeclampsia according to legend.That clusters of preeclamsia occur in family units prompted the question whether preecclampsia is an inherited disorder, and if so, what is the mode of inheritance? Familial clustering opened the possibility of deploying genome wide association studies (GWAS) for the identification of candidate genes and susceptibility loci for the development of preeclampsia and researchers have focused on this question since the discovery of DNA. However, till date, there has been no clearly defined causal relationship between a preeclampsia genotype and phenotype except for heterozygous women who are pregnant with long-chain hydroxyacyl-CoA dehydrogenase deficient fetus who have nearly 80% chance of developing HELLP syndrome or acute fatty liver of pregnancy. Defining the genetics and mode of inheritance of preeclampsia is challenged in part by the involvement of two genomes (maternal and fetal), and a wide spectrum of women who meet the diagnostic criteria according to the International Society for the Study of Hypertension in Pregnancy.There is persuasive literature that coexisting maternal medical disorders such as diabetes, chronic hypertension, renal disease, autoimmune disease, antiphospholipid antibody syndrome and other maternal-fetal risk factors including obesity, dyslipidemia, nulliparity, previous/family history of preeclampsia, and multifetal gestation, increase the risk of preeclampsia. In this issue of the Journal, Gray and colleagues (BJOG 2020 xxxx) used single nucleotide polymorphisms (SNPs) for 21 distinct clinical traits for increased risk of preeclampsia within 7 categories (cardiovascular, inflammatory/ autoimmune, insulin resistance, liver, obesity, renal, and thrombophilia) from the European GWAS to test the hypothesis that women with genetic predisposition to these disorders would have increased risk of preeclampsia in a case/control sample of data from the largest known US preeclampsia GWAS. The authors’ findings that; a) risk alleles for raised diastolic blood pressure and increased BMI were strongly associated with preeclampsia risk (more so for the early-onset disease variant), b) risk alleles for raised alkaline phosphatase levels, increased HDL, GFR, and venous thromboembolism were protective, and c) no significant associations for the other traits examined, are consistent with the current status of preeclampsia and HELLP as highly complex disorders with variable clinical presentations depending on pre-pregnancy maternal conditions, fetal/placental genotypes, and maternal adaptation to the challenge of pregnancy.So, preeclampsia is far from a Mendelian inherited type of genetic disease and the search for its cause and cure continues 90 years after DeLee’s vision!Conflict of interest: None. A completed disclosure of interest form is available to view online as supporting information.

Left ventricular assist devices (LVADs) have become integral to the treatment of advanced heart failure. Surgical bleeding is a known complication of LVAD placement but is most associated with intraperitoneal pump locations. Here we describe a case of massive postoperative hemorrhage secondary to erosion of an intrapericardial LVAD into an intercostal artery with an associated rib fracture.

Background In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection on COVID-19 clinical outcomes. Methods Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. Results We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n=17), Chlamydia pneumoniae (n=13) and human adenovirus (n=10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r=0.1) and higher mortality (OR 1.78, CI=0.38-8.28) compared to bacterial co-infections (OR 0.44, CI=0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r=0.2). Amongst comorbidities, co-infection in patients with diabetes was associated with a significantly higher mortality (p=0.02). We also found that Troponin T was strongly related (p=0.001) with ICU admission and could be used as a predictor of COVID-19 severity. Conclusions The similarity in clinical presentation for both COVID-19 and Influenza makes it difficult to assess their impact on ICU admission and mortality. Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, given the high prevalence of Influenza viruses. The detection of co-infections in COVID-19 cases shows the importance of flu vaccination and warrants its increased coverage to reduce the hospitalization and associated mortality.

A 73-year-old male with a history of severe coronary artery disease and prior CABG presented with chest pain and elevated troponins. His workup revealed an ejection fraction of 10-15% and severe native coronary disease as well as stenosis of bypass grafts. He underwent high-risk redo CABG with Impella 5.5 (Abiomed, Danvers, MA) placement. The Impella was removed on postoperative day eight at which time he went into cardiogenic shock from aortic valve leaflet disruption and severe aortic insufficiency. Given that this patient had severe aortic insufficiency and no calcium deposits around the aortic valve annulus a multidisciplinary heart team decided he would be best served by a surgical aortic valve replacement. He was taken back to the operating room for a surgical aortic valve and intra-aortic balloon pump. His postoperative course was complicated by pneumonia, sepsis, and renal failure requiring continuous renal replacement therapy. He was discharged to rehab after 42 days.

One way in which trichocyte keratin intermediate filament proteins (keratins) and keratin associated proteins (KAPs) differ from their epithelial equivalents is in their higher levels of cysteine residues. Interactions between these cysteine residues within a mammalian fiber, and the putative regular organization of interactions (i.e., types of disulfide bond) are likely important for defining fiber mechanical properties, and thus biological functionality of hairs. Here we extend a previous study of cysteine accessibility under different levels of exposure to reducing compounds to explore a finer set of levels associated with interactions between keratins and KAPs. We found that most of the cysteines in the KAPs were close to either the N- or C- terminal domains of these proteins. The most accessible cysteines in keratins were present in the head or tail domains indicating their function in readily forming intermolecular bonds with KAPs. Some of the more buried cysteines in keratins were discovered either close to or within the rod region in positions previously identified in human epithelial keratins as being involved in crosslinking between the heterodimers of the tetramer. Our present study therefore provides a deeper understanding of the accessibility of disulfides especially in keratins and thus proves that there is some specificity to the disulfide bond interactions leading to these intermolecular bonds stabilizing the fiber structure.

BACKGROUND AND PURPOSE: The α7 and α4β2* (* denotes possibly assembly with another subunit) nicotinic acetylcholine receptors (nAChR) are the most abundant nAChR in the mammalian brain. These subtypes are also the most commonly targeted nAChR in drug discovery programs for brain disorders. However, the development of subtype-specific agonists remains challenging, mainly due to the high degree of sequence homology coupled to the conservation of function in the nAChR family. Here, we determined the structural underpinning of the selectivity of 10-methylcytisine, a compound with high-affinity for α4β2* nAChR but negligible selectivity for the α7 subtype. EXPERIMENTAL APPROACH: The structural underpinning of the receptor selectivity of 10-methylcytisine was investigated using molecular dynamics simulations combined with mutagenesis and whole-cell and single-channel current recordings. KEY RESULTS: We identify a conserved arginine residue in the β3-strand that exhibits a non-conserved salt-bridge in the nAChR family. In α4β2 nAChR, the arginine forms an inter-subunit salt-bridge with an aspartate residue in loop B that is necessary for functional expression, whereas in the α7 subtype, this residue is not stabilised by electrostatic interactions, making its side chain highly mobile. This produces steric clashes with agonists and affects the dynamics of residues involved in agonist binding or the coupling network. CONCLUSIONS AND IMPLICATIONS: We conclude that the high mobility of the arginine residue in the α7 nAChR subtype affects agonist function by influencing agonist binding and the pathway communicating agonist binding to the ion channel. The findings have implications for the rational design of subtype-selective cholinergic agents.

Aim Patients on anti-tuberculosis (anti-TB) therapy are at risk of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) and cytokeratin-18 (K18) are exploratory DILI biomarkers. To explore their utility in this global context, circulating miR-122 and K18 concentrations were measured in UK and Ugandan populations on anti-TB therapy for mycobacterial infection. Methods European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER-ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF-NCT03982277). Serial blood samples, demographic and clinical data were collected. MiR-122 was quantified using PCR. K18 was quantified using the M65 ELISA. Results The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). In the absence of DILI, there was no difference in miR-122 and K18 across the groups. Both miR-122 and K18 correlated with alanine transaminase activity (ALT) (miR-122: r=0.52, 95%CI=0.42-0.61, P<0.0001. K18: r=0.42, 95%CI=0.34-0.49, P<0.0001). There were two DILI cases: baseline ALT was 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR-122 4 and 17 fM, peak miR-122 60 and 336 fM, respectively. Conclusion In European and African patients treated with anti-TB therapy miR-122 and K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of miR-122 and K18 in this global context-of-use.

Introduction: Encorafenib (BraftoviTM) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi ®). According to the product label of encorafenib, there are no specific treatment recommendations in case of an overdose. Case presentation: We report on a 63 year old man who ingested a double dose (900 mg) of encorafenib for 16 days. He developed overall minor chronic intoxication symptoms such as upset stomach, bloating, occasional vomiting and muscle pain. Based on the most occurring adverse events of encorafenib, liver values, kidney function parameters and QTc interval were measured. Kidney function parameters were normal, whereas liver values were slightly increased and QTc slightly prolonged. The plasma concentration 3 hours after the last dose was 2110 ng/mL. Conclusion: We describe the course of a case with a chronic toxicity during 16 days of double dose of encorafenib as well as the followed approach, which could be taken into account when treating a patient with encorafenib intoxication.

The paper deals with blow-up phenomena for the following coupled reaction-diffusion system with nonlocal boundary conditions: \begin{equation*} \left\{\begin{aligned} &u_t=\nabla\cdot\big(\rho_1(u)\nabla u\big)+a_1(x)f_1(v),~~v_t=\nabla\cdot\big(\rho_2(v)\nabla v\big)+a_2(x)f_2(u),&(x,t)\in D\times(0,T),~~\\ &\frac{\partial u}{\partial \nu}=k_1(t)\int_D g_1(u) {\rm d }x,~~\frac{\partial v}{\partial \nu}=k_2(t)\int_D g_2(v) {\rm d }x,&(x,t)\in\partial D\times(0,T),\\ &u(x,0)=u_0(x),~~v(x,0)=v_0(x),\quad &x\in \overline{D}.~~~~~~~~~~~~~~~~~ \end{aligned}\right. \end{equation*} Based some differential inequalities and Sobolev inequality, we establish conditions on the data to guarantee the occurrence of the blow-up. Moreover, when the blow-up occurs, explicit lower and upper bounds on blow-up time are obtained. At last, an example is presented to illustrate our main results.

This paper presents the particle swarm optimization algorithm and immune particle swarm optimization algorithm (PSO-IPSO) to solve the single-leader-multi-follower game (SLMFG). The PSO-IPSO algorithm is designed by combining particle swarm algorithm and immune memory mechanism, and the diversity of the population is maintained by using probability density selection function. Meanwhile, we define the efficiency Nash equilibrium by using the idea of efficiency, which is more beneficial to all players and greatly refine Nash equilibrium. Finally, numerical experiments show that this algorithm not only does not rely on the choice of an initial point, but also increases the diversity of swarm to keep global convergence, and the PSO-IPSO algorithm is fast convergence speed and effective.

People’s preferences influence national priorities for economic development and ecological integrity. Often policy makers and development agents base their actions on unclear assumptions about people’s preferences. This paper explores rural citizens’ preferences for economic and ecological development goals and how they differ within and between communities. We collected data from three purposely selected communities representing dominant social-ecological systems in the transboundary Cubango-Okavango River Basin in southern Africa. We used contingent ranking survey experiments, which are a novel methodological advance in policy related research. This included a qualitative experimental design process that provided a broad framing underpinning the research. The contingent ranking itself allowed us to simultaneously assess (i) participants’ ranking priorities for the development goals; and (ii) participants’ preferences for the ordering of those goals. We found relatively strong preference homogeneity within and between communities. Economic development attributes were given high priority across all communities. At the same time, all communities expressed a high preference for a healthy river system providing stable water quality and quantity. This does not mean that our respondents prioritized nature conservation. They showed low preferences for preserving biodiversity and forests which provide less important local benefits than water. This is of high governance relevance. The results point at development domains where policy makers can most likely expect stronger buy-in from citizens. Understanding citizens’ preferences helps to better align national development priorities with what citizens want.