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Zoonotic disease surveillance is typically triggered after animal pathogens have already infected humans. Are there ways to identify high-risk viruses before they emerge in humans? If so, then how and where can identifications be made and by what methods? These were the fundamental questions driving a workshop to examine the future of predictive surveillance for viruses that might jump from animals to infect humans. Virologists, ecologists and computational biologists from academia, federal government and non-governmental organizations discussed opportunities as well as obstacles to the prediction of species jumps using genetic and ecological data from viruses and their hosts, vectors and reservoirs. This workshop marked an important first step towards envisioning both scientific and organizational frameworks for this future capability. Canine parvoviruses as well as seasonal H3N2 and pandemic H1N1 influenza viruses are discussed as exemplars that suggest what to look for in anticipating species jumps. To answer the question of where to look, prospects for discovering emerging viruses among wildlife, bats, rodents, arthropod vectors and occupationally exposed humans are discussed. Finally, opportunities and obstacles are identified and accompanied by suggestions for how to look for species jumps. Taken together, these findings constitute the beginnings of a conceptual framework for achieving a virus surveillance capability that could predict future species jumps.

Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats and humans live in close proximity in urban environments, there exists potential for transmission. To identify zoonotic agents carried by rats in Baltimore, Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a panel of viruses, bacteria, and parasites. Antibodies against Seoul virus (57.7%), hepatitis E virus (HEV, 73.5%), Leptospira interrogans (65.3%), Bartonella elizabethae (34.1%), and Rickettsia typhi (7.0%) were detected in Norway rats. Endoparasites, including Calodium hepatica (87.9%) and Hymenolepis sp. (34.4%), and ectoparasites (13.9%, primarily Laelaps echidninus) also were present. The risk of human exposure to these pathogens is a significant public health concern. Because these pathogens cause non-specific and often self-limiting symptoms in humans, infection in human populations is probably underdiagnosed. [ABSTRACT FROM AUTHOR]

Hantavirus cardiopulmonary syndrome (HCPS), a rodent-borne zoonosis, has been endemic in the Americas for at least several decades. It is hypothesized that the 1991-1992 El Nino-southern oscillation (ENSO) caused increased precipitation that allowed an increase in rodent population densities, thereby increasing the possibility of transmission to humans. The result was a 1993-1994 outbreak of the disease in the Four Corners states of the southwestern United States. A second strong ENSO occurred in 1997-1998, after a period of considerable public education about the risks of hantavirus infection that began during the 1993-1994 outbreak. The caseload of HCPS increased 5-fold above baseline in the Four Corners states in 1998-1999. Regions that had received increased rainfall in 1998 were especially affected. A large majority of the 1998-1999 case patients reported indoor exposure to deer mice. Hantavirus outbreaks can occur in response to abiotic events, even in the face of extensive public education and Copyright © 2000 The University of Chicago [ABSTRACT FROM AUTHOR]

Background: The mosquito-borne dengue viruses are a major public health problem throughout the tropical and subtropical regions of the world. Changes in temperature and precipitation have well-defined roles in the transmission cycle and may thus play a role in changing incidence levels. The El Niño Southern Oscillation (ENSO) is a multiyear climate driver of local temperature and precipitation worldwide. Previous studies have reported varying degrees of association between ENSO and dengue incidence.Methods and Findings: We analyzed the relationship between ENSO, local weather, and dengue incidence in Puerto Rico, Mexico, and Thailand using wavelet analysis to identify time- and frequency-specific association. In Puerto Rico, ENSO was transiently associated with temperature and dengue incidence on multiyear scales. However, only local precipitation and not temperature was associated with dengue on multiyear scales. In Thailand, ENSO was associated with both temperature and precipitation. Although precipitation was associated with dengue incidence, the association was nonstationary and likely spurious. In Mexico, no association between any of the variables was observed on the multiyear scale.Conclusions: The evidence for a relationship between ENSO, climate, and dengue incidence presented here is weak. While multiyear climate variability may play a role in endemic interannual dengue dynamics, we did not find evidence of a strong, consistent relationship in any of the study areas. The role of ENSO may be obscured by local climate heterogeneity, insufficient data, randomly coincident outbreaks, and other, potentially stronger, intrinsic factors regulating transmission dynamics. [ABSTRACT FROM AUTHOR]

In 1992, Baltimore Mayor Kurt L. Schmoke created the Rodent Control Committee to combat the increasing Norway rat population in Baltimore City. Following a pilot project, programs were conducted in two sections of the city from which high numbers of rat complaints had been reported. These three-month programs attacked the rodent problem via an integrated pest management approach that emphasized public education by trained community leaders and health department workers, increased community cleanup projects coordinated by the Bureau of Solid Waste, and intensified baiting by the city's Rat Rubout Program. Direct intervention eliminated up to 90 percent of rat burrows present in the target neighborhoods. Follow-up surveys, however, showed that in neighborhoods with environmental factors favoring rat populations, reinfestations achieved preintervention levels within six months. Attempts to modify the behavior of residents, which is vital in reducing and eliminating rodent infestation, were generally unsuccessful. [ABSTRACT FROM AUTHOR]

Background: Body contouring surgery removes excess skin and fat, often after massive weight loss. Some reports suggest that patients who have previously undergone obesity (bariatric) surgery are at excess risk of subsequent bleeding, possibly due to complex nutritional and metabolic sequelae of massive weight loss., Methods: A retrospective cohort study of intraoperative blood loss and postoperative bleeding indicators were examined for patients who had undergone abdominoplasty. Participants were categorized based on their history of previous obesity surgery, and outcome variables were compared using odds ratio, followed by subgroup comparison between a history of restrictive versus malabsorptive obesity surgery., Results: The study included 472 patients, of which 171 (36.2 %) had a history of obesity surgery. Mean age was 40.4 years, and 402 (85.1%) participant were women. Fifty-five (11.6%) patients were smokers whereas 65 (13.7%) were hypertensive. Mean body mass index before surgery was 30.2 kg per m 2 , and average time between obesity and body contouring surgery (if applicable) was 35.8 months. Patients with a history of obesity surgery exhibited greater intraoperative blood loss (162.2 mL versus 132.1 mL; P = 0.001), drainage volume at 24 h (155 mL versus 135 mL; P = 0.001), and total drainage volume (300ml versus 220 mL; P = 0.001). Postoperative hematoma requiring surgical re-exploration was almost three times higher following a history of obesity surgery (4.7% versus 1.7 %; P = 0.05)., Conclusions: History of obesity surgery increases intraoperative blood loss, postoperative serosanguinous drainage volumes, and the risk of postoperative hematoma requiring surgical evacuation after abdominal body contouring procedures., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. This study was supported by the Qatar National Library., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: The risk and metabolic effects of obesity are determined by the distribution of fat throughout the body. It has been proposed that the distribution of abdominal fat is more closely related to the metabolic risks of obesity. High prevalence of overweight and obesity has thereby contributed to an increased uptake of surgical subcutaneous fat removal (SSFR) procedures. The goal of this study was to determine whether bioelectrical impedance analysis (Tanita system) can be used to detect the removal of excess abdominal subcutaneous fat tissue during SSFR when studying the metabolic effects of such procedures. Methods: Study population comprised patients who received body contouring procedures at the Hamad General Hospital's plastic surgery department between November 2020 and December 2022. To evaluate the factors of interest, subjects were prospectively followed up at two time points: within 1 week before the surgery and within 1-2 weeks thereafter. The following factors were measured: body weight, body fat percentage, body fat mass, body mass index (BMI), fat-free mass, estimated muscle mass, total body water, visceral fat score, and basal metabolic rate. Results: In total, 22 patients were included in the study. The two visits' medians for height, weight, BMI, fat percent (fat%), fat mass, visceral fat rating, and Doi's weighted average glucose (dwAG) were compared. Only in the case of Tanita fat% and fat mass, were the preoperative and postoperative medians significantly different. Furthermore, there was no association between these Tanita measures and dwAG or homeostatic model assessment (HOMA; insulin resistance [IR]) changes (before and after surgery). Tanita measures overestimated fat loss, as seen by the mountain plot and Bland-Altman plot agreement methods. Conclusions: Our findings indicated that the only two Tanita measures exhibited meaningful early associations with the amount of tissue excised which were fat mass and fat% differences. Although dwAG and HOMA-IR are not impacted immediately postsurgery, a trend was seen that suggested improvements in those parameters, even though the changes are not clinically significant.

Hantaviral diseases have been recognized as 'place diseases' from their earliest identification and, epidemiologically, are tied to single host species with transmission occurring from infectious hosts to humans. As such, human populations are most at risk when they are in physical proximity to suitable habitats for reservoir populations, when numbers of infectious hosts are greatest. Because of the lags between improving habitat conditions and increasing infectious host abundance and spillover to humans, it should be possible to anticipate (forecast) where and when outbreaks will most likely occur. Most mammalian hosts are associated with specific habitat requirements, so identifying these habitats and the ecological drivers that impact population growth and the dispersal of viral hosts should be markers of the increased risk for disease outbreaks. These regions could be targeted for public health and medical education. This paper outlines the rationale for forecasting zoonotic outbreaks, and the information that needs to be clarified at various levels of biological organization to make the forecasting of orthohantaviruses successful. Major challenges reflect the transdisciplinary nature of forecasting zoonoses, with needs to better understand the implications of the data collected, how collections are designed, and how chosen methods impact the interpretation of results.

The Costa Rican pygmy rice rat ( Oligoryzomys costaricensis ) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Photobiomodulation (PBM) therapy is an increasingly popular modality for aesthetic skin rejuvenation. PBM induces genomic, proteomic, and metabolomic processes within target cells, but such manipulation of cell behavior has led to concerns about oncologic safety. This article presents a summary of the clinical and preclinical evidence for the oncologic safety of PBM for aesthetic skin rejuvenation. A focused systematic review was performed, in which safety data from clinical trials of PBM for skin rejuvenation was supplemented by analyses of in vitro data obtained from cells derived from human skin and human neoplastic cells and in vivo data of tumors of the skin, oral cavity, and breast. Within established parameters, red and near infrared light mainly enhances proliferation of healthy cells without a clear pattern of influence on cell viability. The same light parameters mainly reduce neoplastic cell proliferation and viability or else make no difference. Invasiveness potential (appraised by cell migration assays and/or differential gene expression) is equivocal. PBM does not induce dysplastic change in healthy cells. In vivo tumor models yield varied results with no clear pattern emerging. There are no relevant clinical trial data linking PBM with any significant adverse events, including the finding of a new or recurrent malignancy.Current clinical and preclinical evidence suggests that PBM is oncologically safe for skin rejuvenation, and there is no evidence to support the proposition that it should be avoided by patients who have previously undergone treatment for cancer., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Obesity-induced insulin resistance leads to the metabolic syndrome. Both bariatric surgery and surgical fat removal have been shown to improve metabolic health, but the metabolic benefits of nonsurgical fat removal remain uncertain. The aim of this paper is to establish whether nonsurgical fat removal exerts measurable, lasting metabolic benefits by way of changes to serum lipid profiles., Methods: PubMed, Cochrane CENTRAL, Embase, and clinical trials registers were searched using the Polyglot Search Translator to find studies examining quantitative changes in metabolic markers after nonsurgical body contouring procedures. The MethodologicAl STandard for Epidemiological Research (MASTER) scale was adopted for the quality assessment of the included studies. The robust-error meta-regression (REMR) model was employed., Results: Twenty-two studies and 676 participants were included. Peak body compositions measures manifest as a reduction of 2 units in body mass index (BMI), 1 kg of body weight (BW), 5 cm in waist circumference (WC) and 1.5 cm in abdominal fat thickness (FT), sustained up to 60 days postprocedure. Transient increases of 15 mg/dL in low-density lipoprotein (LDL), 10 mg/dl in triglycerides (TG), and 15 mg/dl in total cholesterol (TC) were observed at 2 weeks postprocedure., Conclusion: While nonsurgical fat removal exerts sustained effects on body anthropometrics, changes to serum lipid profiles were transient. There is no compelling evidence at present to support the conclusion that nonsurgical fat removal is metabolically beneficial., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Bariatric surgery averts obesity-induced insulin resistance and the metabolic syndrome. By contrast, surgical fat removal is considered merely an esthetic endeavor. The aim of this article was to establish whether surgical fat removal, similar to bariatric surgery, exerts measurable, lasting metabolic benefits., Methods: PubMed, Embase, and Scopus were searched using the Polyglot Search Translator to find studies examining quantitative expression of metabolic markers. Quality assessment was done using the MethodologicAl STandard for Epidemiological Research scale. The robust-error meta-regression model was employed for this synthesis., Results: Twenty-two studies with 493 participants were included. Insulin sensitivity improved gradually with a maximum reduction in fasting insulin and homeostatic model assessment for insulin resistance of 17 pmol/L and 1 point, respectively, at postoperative day 180. Peak metabolic benefits manifest as a reduction of 2 units in body mass index, 3 kg of fat mass, 5 cm of waist circumference, 15 µg/L of serum leptin, 0.75 pg/ml of tumor necrosis factor-alpha, 0.25 mmol/L of total cholesterol, and 3.5 mmHg of systolic and diastolic blood pressure that were observed at day 50 but were followed by a return to preoperative levels by day 180. Serum high-density lipoproteins peaked at 50 days post-surgery before falling below the baseline. No significant changes were observed in lean body mass, serum adiponectin, resistin, interleukin-6, C-reactive protein, triglyceride, low-density lipoproteins, free fatty acids, and fasting blood glucose., Conclusion: Surgical fat removal exerts several metabolic benefits in the short term, but only improvements in insulin sensitivity last beyond 6 months., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Möbius (Moebius) and Poland's syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6 th and 7 th cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors. The PLXND1 gene codes for a protein expressed in the fetal central nervous system and vascular endothelium and is thus involved in embryonic neurogenesis and vasculogenesis. It is located at chromosome region 3q21-q22, a locus of interest for Möbius syndrome., Case Presentation: We present the first report of a patient with Poland-Möbius syndrome and a mutation in the PLXND1 gene. A child with Poland-Möbius syndrome and a maternally inherited missense variant (NM_015103.2:ex14:c.2890G > Ap.V964M) in the PLXND1 gene is described. In order to contextualize these findings, the literature was examined to identify other confirmed cases of Poland-Möbius syndrome for which genetic data were available. Fourteen additional cases of Poland-Möbius syndrome with genetic studies are described in the literature. None implicated the PLXND1 gene which has previously been implicated in isolated Möbius syndrome., Conclusions: This report provides further evidence in support of a role for PLXND1 mutations in Möbius syndrome and reasserts the nosological link between Möbius and Poland's syndromes., Level of Evidence: Level V, Descriptive Study., (© 2022. The Author(s).)

Introduction: Published standards for the management of open extremity fractures have improved limb salvage, fracture union, and deep infection rates, but the aesthetic and functional importance of our flap choices has been overlooked. Thin and superthin free flaps exhibit advantages over traditional free flaps in some situations but have seldom been reported in children. The aim of this paper is to present our experience of thin and superthin free flaps in pediatric extremity reconstruction., Methods: Children (≤13 years) who underwent soft tissue reconstruction using a thin and superthin free flap following major extremity trauma are presented., Results: Five patients (5 flaps) met the inclusion criteria. The median age was 9 (range 6-13). There were 3 Gustilo IIIB open fractures and 2 multiplanar degloving injuries. The median mangled extremity severity score (MESS) was 4 (range 2-6). The median time from injury to definitive soft tissue closure was 72 h (range 28-120 h). Four anterolateral thigh (ALT) flaps were raised as thin flaps, and 1 superficial circumflex iliac artery perforator (SCIP) was raised as a superthin flap. There was one re-exploration owing to venous congestion, and a second venous anastomosis was performed to enhance flap drainage. The same ALT flap exhibited necrosis at one margin, which was debrided and grafted before discharge. There were no other flap complications. No flap-related secondary surgeries were required., Conclusion: Thin and superthin free flaps are viable options in pediatric extremity reconstruction. They exhibit excellent aesthetic and functional contouring when a slender fasciocutaneous flap is needed, especially when body habitus renders traditional options unfavorable., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare, (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Extremity ischemia and necrosis after jellyfish envenomation can be mutilating and cause long-term functional deficits. The best way to manage these presentations is unknown., Objective: The aim of this review was to establish an evidence-based consensus for the management of extremity ischemia after jellyfish envenomation., Methods: A systematic review of cases of extremity ischemia and necrosis after envenomation by marine cnidarians was performed to clarify what is and what is not known about management and outcomes, to draw conclusions about how best to manage these rare presentations, and to establish an evidence-based algorithm., Results: The ischemic sequelae of envenomation typically evolves over a few days. Close medical supervision is necessary to react promptly to the evolving clinical scenario. In the literature, 15 different pharmacologic classes have been used to manage these presentations. Only IV infusions of prostaglandin derivatives and intra-arterial thrombolytics have been found to improve the clinical picture and avoid the need for surgical fasciotomy and debridement in some cases. Anticoagulants, antiplatelet agents, steroids, antibiotics, and nitrates, which are among the most commonly prescribed pharmacologic agents, have not been observed to alter the clinical picture., Conclusions: Surgery for compartment syndrome and necrosis are common sequelae of extremity envenomation by marine cnidarians. Only prompt use of IV prostaglandins or intra-arterial thrombolytics can halt ischemic progression and avoid the need for surgery. An algorithm is proposed to guide management of these rare and mutilative presentations., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mapping asymptomatic malaria infections, which contribute to the transmission reservoir, is important for elimination programs. This analysis compared the spatiotemporal patterns of symptomatic and asymptomatic Plasmodium falciparum malaria infections in a cohort study of ∼25,000 people living in a rural hypoendemic area of about 179 km2 in a small area of the Chittagong Hill Districts of Bangladesh. Asymptomatic infections were identified by active surveillance; symptomatic clinical cases presented for care. Infections were identified by a positive rapid diagnostic test and/or microscopy. Fifty-three subjects with asymptomatic P. falciparum infection were compared with 572 subjects with symptomatic P. falciparum between mid-October 2009 and mid-October 2012 with regard to seasonality, household location, and extent of spatial clustering. We found increased spatial clustering of symptomatic compared with asymptomatic infections, and the areas of high intensity were only sometimes overlapping. Symptomatic cases had a distinct seasonality, unlike asymptomatic infections, which were detected year-round. In a comparison of 42 symptomatic Plasmodium vivax and 777 symptomatic P. falciparum cases from mid-October 2009 through mid-March 2015, we found substantial spatial overlap in areas with high infection rates, but the areas with the greatest concentration of infection differed. Detection of both symptomatic P. falciparum and symptomatic P. vivax infections was greater during the May-to-October high season, although a greater proportion of P. falciparum cases occurred during the high season compared with P. vivax. These findings reinforce that passive malaria surveillance and treatment of symptomatic cases will not eliminate the asymptomatic reservoirs that occur distinctly in time and space.

Abstract: Facial paralysis can impair one's ability to form facial expressions that are congruent with internal emotion. This hinders communication and the cognitive processing of emotional experience. Facial reanimation surgery, which aims to restore full facial expressivity is a relatively recent undertaking which is still evolving. Due in large part to published techniques, refinements, and clinical outcomes in the scientific literature, consensus on best practice is gradually emerging, whereas controversies still exist.Taking stock of how the discipline reached its current state can help delineate areas of agreement and debate, and more clearly reveal a path forward. To do this, the authors have analyzed the 50 seminal publications pertaining to facial reanimation surgery. In longstanding cases, the free gracilis transfer emerges as a clear muscle of choice but the nerve selection remains controversial with prevailing philosophies advocating cross facial nerve grafts (with or without the support of an ipsilateral motor donor) or an ipsilateral motor donor only, of which the hypoglossal and nerve to masseter predominate. The alternative orthodoxy has refined the approach popularized by Gillies in 1934 and does not require the deployment of microsurgical principles. Although this citation analysis does not tell the whole story, surgeons with an interest in facial reanimation will find that this is a good place to start., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Ensembles of Species Distribution Models (SDMs) represent the geographic ranges of pathogen vectors by combining alternative analytical approaches and merging information on vector occurrences with more extensive environmental data. Biased collection data impact SDMs, regardless of the target species, but no studies have compared the differences in the distributions predicted by the ensemble models when different sampling frameworks are used for the same species. We compared Ensemble SDMs for two important Ixodid tick vectors, Amblyomma americanum and Ixodes scapularis in mainland Florida, USA, when inputs were either convenience samples of ticks, or collections obtained using the standard protocols promulgated by the U.S. Centers for Disease Control and Prevention. The Ensemble SDMs for the convenience samples and standard surveys showed only a slight agreement (Kappa = 0.060, A. americanum ; 0.053, I. scapularis). Convenience sample SDMs indicated A. americanum and I. scapularis should be absent from nearly one third (34.5% and 30.9%, respectively) of the state where standard surveys predicted the highest likelihood of occurrence. Ensemble models from standard surveys predicted 81.4% and 72.5% ( A. americanum and I. scapularis ) of convenience sample sites. Omission errors by standard survey SDMs of the convenience collections were associated almost exclusively with either adjacency to at least one SDM, or errors in geocoding algorithms that failed to correctly locate geographic locations of convenience samples. These errors emphasize commonly overlooked needs to explicitly evaluate and improve data quality for arthropod survey data that are applied to spatial models.

Rare deletions and duplications on the long arm of Chromosome 21 have previously been reported in many patients with craniofacial and developmental phenotypes. However, this Down Syndrome Critical Region (DSCR) contains multiple genes, making identifying a single causative gene difficult. Here, we report a case of a boy with bicoronal craniosynostosis, facial dysmorphism, developmental delay, and intellectual impairment who was found by whole genome sequencing to have a homozygous missense mutation in the Single-Minded Homolog 2 (SIM2) gene (c.461 A > G, p.Tyr154Cys) within the DSCR. SIM2 encodes an essential bHLH and PAS domain transcription factor expressed during fetal brain development and acts as a master regulator of neurogenesis. This variant is globally very rare, segregates in the family, and is predicted to be highly deleterious by in silico analysis, 3D molecular modeling of protein structure, and functional analysis of zebrafish models. Zebrafish expressing the human SIM2 p.Y154C variant displayed a progressed microcephaly-like phenotype and head shape abnormalities. When combined with careful phenotyping of the patient vis-à-vis previously reported cases harboring structural variants in this critical 21q22 region, the data support a pathogenic role of SIM2 in this complex syndrome and demonstrates the utility of next-generation sequencing in prioritizing genes in contiguous deletions/duplications syndromes and diagnosing microarray-negative patients in the craniofacial clinic., (Copyright © 2022. Published by Elsevier Masson SAS.)

In Europe, two species of hantaviruses, Puumala orthohantavirus (PUUV) and Dobrava orthohantavirus (DOBV), cause hemorrhagic fever with renal syndrome in humans. The rodent reservoirs for these viruses are common throughout Ukraine, and hence, the goal of this study was to identify the species and strains of hantaviruses circulating in this region. We conducted surveillance of small rodent populations in a rural region in northwestern Ukraine approximately 30 km from Poland. From the 424 small mammals captured, we identified nine species, of which the most abundant were Myodes glareolus , the bank vole (45%); Apodemus flavicollis , the yellow-necked mouse (29%); and Apodemus agrarius , the striped field mouse (14.6%) Using an indirect immunofluorescence assay, 15.7%, 20.5%, and 33.9% of the sera from M. glareolus , A. glareolus , and A. flavicollis were positive for hantaviral antibodies, respectively. Additionally, we detected antibodies to the hantaviral antigen in one Microtus arvalis , one Mus musculus , and one Sorex minutus . We screened the lung tissue for hantaviral RNA using next-generation sequencing and identified PUUV sequences in 25 small mammals, including 23 M. glareolus , 1 M. musculus , and 1 A. flavicollis, but we were unable to detect DOBV sequences in any of our A. agrarius specimens. The percent identity matrix and Bayesian phylogenetic analyses of the S-segment of PUUV from 14 M. glareolus lungs suggest the highest similarity (92-95% nucleotide or 99-100% amino acid) with the Latvian lineage. This new genetic information will contribute to future molecular surveillance of human cases in Ukraine.

Background: Low-level light therapy (LLLT) is a recent addition to the pantheon of light-based therapeutic interventions. The absorption of red/near-infrared light energy, a process termed "photobiomodulation," enhances mitochondrial ATP production, cell signaling, and growth factor synthesis, and attenuates oxidative stress. Photobiomodulation is now highly commercialized with devices marketed directly to the consumer. In the gray area between the commercial and therapeutic sectors, harnessing the clinical potential in reproducible and scientifically measurable ways remains challenging., Objectives: The aim of this article was to summarize the clinical evidence for photobiomodulation and discuss the regulatory framework for this therapy., Methods: A review of the clinical literature pertaining to the use of LLLT for skin rejuvenation (facial rhytids and dyschromias), acne vulgaris, wound healing, body contouring, and androgenic alopecia was performed., Results: A reasonable body of clinical trial evidence exists to support the role of low-energy red/near-infrared light as a safe and effective method of skin rejuvenation, treatment of acne vulgaris and alopecia, and, especially, body contouring. Methodologic flaws, small patient cohorts, and industry funding mean there is ample scope to improve the quality of evidence. It remains unclear if light-emitting diode sources induce physiologic effects of compararable nature and magnitude to those of the laser-based systems used in most of the higher-quality studies., Conclusions: LLLT is here to stay. However, its ubiquity and commercial success have outpaced empirical approaches on which solid clinical evidence is established. Thus, the challenge is to prove its therapeutic utility in retrospect. Well-designed, adequately powered, independent clinical trials will help us answer some of the unresolved questions and enable the potential of this therapy to be realized., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Tick-borne pathogens are of growing concern. The U.S. Centers for Disease Control and Prevention (CDC) developed guidelines standardizing surveys of tick vectors to better monitor the changes in their occurrences. Unbiased surveillance data, from standardized surveys, are presumed critical to generate valid species distribution models (SDMs). We tested previously generated SDMs from standardized protocols for three medically important ticks [Amblyomma americanum (Linnaeus, Ixodida, Ixodidae), Ixodes scapularis (Say, Ixodida, Ixodidae), and Dermacentor variabilis (Say, Ixodida, Ixodidae)]. These previous models ruled out a quarter to half of the state as having these species, with consensus occurrence in about a quarter of the state. New surveys performed throughout 2019 on 250 transects at 43 sites indicated the rule-out functions were 100% accurate for I. scapularis and D. variabilis and 91.9% for A. americanum. As SDM concordance increased, the proportion of transects yielding ticks increased. Independent surveys of SDMs provide external validation-an aspect missing from many SDM studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America.)

Light energy is harnessed for therapeutic use in a number of ways, most recently by way of photobiomodulation (PBM). This phenomenon is a cascade of physiological events induced by the nonthermal exposure of tissue to light at the near infrared end of the visible spectrum. Therapeutic PBM has become a highly commercialized interest, marketed for everything from facial rejuvenation to fat loss, and diode-based devices are popular in both the clinic setting and for use at home. The lack of regulatory standards makes it difficult to draw clear conclusions about efficacy and safety but it is crucial that we understand the theoretical basis for PBM, so that we can engage in an honest dialogue with our patients and design better clinical studies to put claims of efficacy to the test. This article presents a summary of the science of PBM and examines the differences between laser light, on which much of the preclinical evidence is based and light from diodes, which are typically used in a clinical setting., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Florida faces the challenge of repeated introduction and autochthonous transmission of arboviruses transmitted by Aedes aegypti and Aedes albopictus. Empirically-based predictive models of the spatial distribution of these species would aid surveillance and vector control efforts. To predict the occurrence and abundance of these species, we fit a mixed-effects zero-inflated negative binomial regression to a mosquito surveillance dataset with records from more than 200,000 trap days, representative of 53% of the land area and ranging from 2004 to 2018 in Florida. We found an asymmetrical competitive interaction between adult populations of Aedes aegypti and Aedes albopictus for the sampled sites. Wind speed was negatively associated with the occurrence and abundance of both vectors. Our model predictions show high accuracy (72.9% to 94.5%) in validation tests leaving out a random 10% subset of sites and data since 2017, suggesting a potential for predicting the distribution of the two Aedes vectors., Competing Interests: The authors declare no competing financial interests.

Successful public health regimes for COVID-19 push below unity long-term regional R t -the average number of secondary cases caused by an infectious individual. We use a susceptible-infectious-recovered (SIR) model for two coupled populations to make the conceptual point that asynchronous, variable local control, together with movement between populations, elevates long-term regional R t , and cumulative cases, and may even prevent disease eradication that is otherwise possible. For effective pandemic mitigation strategies, it is critical that models encompass both spatiotemporal heterogeneity in transmission and movement., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Social interactions are largely dependent on the interpretation of information conveyed through facial expressions. Although facial reanimation seeks restoration of the facial expression of emotion, outcome measures have not addressed this directly. This study evaluates the use of a machine learning technology to directly measure facial expression before and after facial reanimation surgery. Fifteen study subjects with facial palsy were evaluated both before and after undergoing cross-facial nerve grafting and free gracilis muscle transfer. Eight healthy volunteers were assessed for control comparison. Video footage of subjects with their face in repose and with a posed, closed-lip smile was obtained. The video data were then analyzed using the Noldus FaceReader software application to measure the relative proportions of seven cardinal facial expressions detected within each clip. The facial expression recognition application detected a far greater happy signal in postoperative (42 percent) versus preoperative (13 percent) smile videos (p < 0.0001), compared to 53 percent in videos of control faces smiling. This increase in postoperative happy signal was achieved in exchange for a reduction in the sad signal (15 percent to 9 percent; p = 0.092) and the neutral signal (57 percent to 37 percent; p = 0.0012). For video clips of patients in repose, no significant difference in happy emotion was detected between preoperative (3.1 percent) and postoperative (1.4 percent) states (p = 0.5). This study provides the first proof of concept for the use of a machine learning software application to objectively quantify facial expression before and after surgical reanimation. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, IV.

In Ukraine, a retrospective review of clinical case reports by public health officials suggest that human cases of febrile illnesses associated with hemorrhage may be due to infections of Crimean-Congo hemorrhagic fever virus (CCHFV) and Old World hantaviruses. In a serosurvey of 966 healthy individuals in the Lviv Oblast, Ukraine, bordering Poland, we found that 1.6% showed cross-reactivity to hantaviral antigens by an immunofluorescence assay (IFA) and 1.7% of the study participants had antibodies cross-reactive to CCHFV by enzyme-linked immunosorbent assay (ELISA). Demographic variables and history of exposures obtained through questionnaires were assessed by logistic regression models for association with seroprevalence for both viruses with no significant risk factors found. Analysis of spatial distribution identified two clusters of samples positive for antibodies to both hantaviruses and CCHFV, which, however, were not statistically significant (p > 0.05). In general, the study results suggest that the population of the study area is exposed to hantaviruses and CCHFV. Further surveillance for respective pathogens in Ukraine is warranted and prospective surveillance of febrile patients with unidentified febrile illness., (Copyright © 2020 Lozynskyi, Shulgan, Zarichna, Ben, Kessler, Cao, Nesterova, Glass, Spruill-Harrell, Taylor, Williams and Jonsson.)

Background: Aesthetic practice relies on a harmonious relationship between medicine and commerce. Bridging the gap is a large number of skincare products that make therapeutic claims while avoiding the regulatory framework of pharmaceuticals. In this gray area, clinicians find themselves poorly disposed to counsel patients wisely as the industry is expanding faster than empirical evidence of efficacy and safety can be acquired. To serve our patients and engage with industry, we must understand the theoretical principles and evaluate the clinical evidence in practice., Objectives: The purpose of this paper is to classify cosmeceuticals by method of action, explain how they work in principle with reference to skin aging, and evaluate the clinical evidence for them., Methods: A literature and cosmetic clinic website search was conducted to establish a list of the most commonly advertised cosmeceuticals, and a peer-reviewed literature search was then conducted to establish the clinical evidence for them., Results: A huge number of cosmeceuticals are marketed for skin rejuvenation but almost invariably they fall into 1 of 4 categories. These include the induction of tissue repair mechanisms, inflammatory modulation, scavenging of reactive oxygen species, or a combination of the 3. With the exception of retinol derivatives and hydroxy acids, the clinical evidence is limited, despite promising preclinical evidence for several cosmeceuticals., Conclusions: Cosmeceuticals reside within a highly competitive ecosystem and are often brought to market based on preclinical, not clinical evidence. Success and failure will largely be governed by the establishment of clinical evidence in retrospect., (© 2020 The Aesthetic Society.)

Rodent-borne hantaviruses have been reported in many of the countries surrounding Ukraine; however, to date we have no knowledge of the viral strains circulating in Ukraine within reservoirs such as the striped field mouse ( Apodemus agrarius ), the yellow-necked field mouse ( Apodemus flavicollis ), and the bank vole ( Myodes glareolus ). To determine the prevalence of hantaviruses in Ukraine, we captured 1,261 mammals, of which 1,109 were rodents, in 58 field sites within the province of Volyn in western Ukraine. Foci of the striped field mouse tended to occur in the eastern and southern parts of the province, whereas the bank vole were clustered in western and northern regions. The striped field mouse and bank vole had detectable serum antibodies to Puumala virus (PUUV) or Dobrava virus (DOBV) antigens at 7% or 2%, respectively, using an indirect immunofluorescence assay. Antibody prevalence among the bank vole males and females was equivalent, whereas for the striped field mouse, the prevalence among males was 5% versus 1% for females. In two bank vole specimens, we were able to detect partial nucleotide sequences that showed identity to PUUV. In summary, this study suggests that two human pathogens, PUUV and DOBV, cocirculate in the bank vole and the striped field mouse, respectively, in Ukraine. Future studies will focus on new rodent collections that will enable obtaining the complete genome sequences of the PUUV and DOBV strains circulating in Ukraine to provide guidance on the design of optimal molecular diagnostics that can enable insight into the potential contribution of hantaviruses to human disease in Ukraine.

Penetrating orbital trauma in the pediatric population is rare. Even more unusual is a secondary orbital infection following penetrating trauma. Here we present a highly unusual case of fulminant facial cellulitis with an orbital abscess in an otherwise healthy 3-year-old boy following a penetrating injury to the orbit from a point of entry on the gingiva-buccal sulcus, sustained during a fall while carrying a wooden lollipop stick. Examination of the retina revealed a focal injury at the inferior pole of the globe. The organisms cultured from pus sampled from the abscess and from the discharging intraoral wound revealed the same oral commensals while the MRI revealed a track in continuity with the orbital collection.

Background: Many prospective patients remain wary of the effects that glabellar muscle paralysis may have on their ability to normally communicate emotion with their face., Objective: We undertook a direct empirical test of the effects of glabellar onabotulinum toxin type A injections on the ability to convey 6 universally recognized facial expressions of emotion., Methods: Fifty-two female subjects ("expressors") were recorded on hidden camera while viewing video clips intended as a mood induction procedure that stimulates the 6 cardinal emotions (amusement, anger, disgust, fear, sadness, surprise). The subjects were then injected with 25 units of onabotulinum toxin A in the glabellar region. The subjects returned 1 month later and were again recorded while being spontaneously induced to express emotion. All video clips from both time periods from the 10 maximal expressors were extracted and shown to a group of 31 "perceivers" who rated the facial expressions for intensity (Likert 1-7) and identity of emotion (percent correct emotion identified)., Results: Glabellar paralysis significantly diminished mean perceived intensity of anger (50.4% relative reduction, P < 0.001) and surprise (20.6% relative reduction, P < 0.001). The mean intensity of disgust increased (39.0%, P < 0.001). Importantly, however, glabellar paralysis did not result in a significant change in observers' ability to discern provoked cardinal emotions., Conclusions: We believe these findings provide a measure of reassurance to patients and their providers that the use of onabotulinum toxin A to paralyze the glabellar musculature for aesthetic purposes may not pose a meaningful risk to the overall ability to express emotion during social interaction., (© 2019 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Rhinoplasty utilizes cartilage harvested from the nasal septum as autologous graft material. Traditional dogma espouses preservation of the "L-strut" of dorsal and caudal septum, which is less resistant to axial loading than virgin septum. Considering the 90° angle between dorsal and caudal limbs, the traditional L-strut also suffers from localized increases in internal stresses leading to premature septal "cracking," structural-scale deformation, or both. Deformation and failure of the L-strut leads to nasal deviation, saddle deformity, loss of tip support, or restriction of the nasal valve. The balance between cartilage yield and structural integrity is a topographical optimization problem. Guided by finite element (FE) modelling, recent efforts have yielded important modifications including the chamfering of right-angled corners to reduce stress concentrations and the preservation of a minimum width along the inferior portion of the caudal strut. However, all existing FE studies offer simplified assumptions to make the construct easier to model. This review article highlights advances in our understanding of septal engineering and identifies areas that require more work to further refine the balance between the competing interests of graft acquisition and the maintenance of nasal structural integrity., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Actinomycosis is a rare disease that remains difficult to diagnose and manage. Prompted by 2 recent cases the authors sought evidence-based conclusions about best practice. A systematic review was conducted using standard PRISMA methodology. The study was registered prospectively (PROSPERO: CRD42018115064). Thirty-three children from 23 series are described. The mean age was 8 years (range 3-17). Fifty-five percent were female. Twenty cases involved bone (usually mandible); 13 cases involved cervicofacial soft tissue. Poor dental hygiene and oral trauma were implicated. The median diagnostic delay was 12 weeks (range 1-156 weeks). The median duration of definitive antibiotic therapy was 17 weeks (range 1-130 weeks). Although diagnostic delay did not correlate with number of surgeries, bony involvement was associated with more procedures (P = 0.008, unpaired t test). All (6) cases with residual infection had bony involvement (P = 0.06, Fisher exact test). Neither diagnostic delay nor number of surgeries significantly influenced infection-free outcome which, instead, relies on aggressive surgical debridement and prolonged antibiotic therapy. Mandibular involvement exhibits a higher surgical burden and chronicity in around a third of cases. As dental caries are implicated in mandibular disease, preventative strategies must focus on improving pediatric oral hygiene.

Globally, vector-borne diseases are an increasing public health burden; in the United States, tick-borne diseases have tripled in the last three years. The United States Centers for Disease Control and Prevention (CDC) recognizes the need for resilience to the increasing vector-borne disease burden and has called for increased partnerships and sustained networks to identify and respond to the most pressing challenges that face vector-borne disease management, including increased surveillance. To increase applied research, develop communities of practice, and enhance workforce development, the CDC has created five regional Centers of Excellence in Vector-borne Disease. These Centers are a partnership of public health agencies, vector control groups, academic institutions, and industries. This special issue on tick and tick-borne disease surveillance is a collection of research articles on multiple aspects of surveillance from authors that are affiliated with or funded by the CDC Centers of Excellence. This body of work illustrates a community-based system of research by which participants share common problems and use integrated methodologies to produce outputs and effect outcomes that benefit human, animal and environmental health., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Within the past three decades, new bacterial etiological agents of tick-borne disease have been discovered in the southeastern U.S., and the number of reported tick-borne pathogen infections has increased. In Florida, few systematic studies have been conducted to determine the presence of tick-borne bacterial pathogens. This investigation examined the distribution and presence of tick-borne bacterial pathogens in Florida. Ticks were collected by flagging at 41 field sites, spanning the climatic regions of mainland Florida. DNA was extracted individually from 1608 ticks and screened for Anaplasma , Borrelia , Ehrlichia and Rickettsia using conventional PCR and primers that amplified multiple species for each genus. PCR positive samples were Sanger sequenced. Four species of ticks were collected: Amblyomma americanum , Amblyomma maculatum , Dermacentor variabilis, and Ixodes scapularis . Within these ticks, six bacterial species were identified: Borrelia burgdorferi , Borrelia lonestari , Ehrlichia ewingii , Rickettsia amblyommatis , Rickettsia andeanae , Rickettsia parkeri , and Rickettsia endosymbionts. Pathogenic Borrelia , Ehrlichia , and Rickettsia species were all detected in the North and North-Central Florida counties; however, we found only moderate concordance between the distribution of ticks infected with pathogenic bacteria and human cases of tick-borne diseases in Florida. Given the diversity and numerous bacterial species detected in ticks in Florida, further investigations should be conducted to identify regional hotspots of tick-borne pathogens.

Worldwide, landslides incur catastrophic and significant economic and human losses. Previous studies have characterized the patterns in landslides' fatalities, from all kinds of triggering causes, at a continental or global scale, but they were based on data from periods of <10 years. The research herein presented hypothesizes that climate change associated with extreme rainfall and population distribution is contributing to a higher number of deadly landslides worldwide. This study maps and identified deadly landslides in 128 countries and it encompasses their role, for a 20 years' period from January/1995 to December/2014, considered representative for establishing a relationship between landslides and their meteorological triggers. A database of georeferenced landslides, their date, and casualties' information, duly validated, was implemented. A hot spot analysis for the daily record of landslide locations was performed, as well as a percentile-based approach to evaluate the trend of extreme rainfall events for each occurrence. The relationship between casualty, population distribution, and rainfall was also evaluated. For 20 years, 3876 landslides caused a total of 163,658 deaths and 11,689 injuries globally. They occurred most frequently between June and December in the Northern Hemisphere, and between December and February in the Southern Hemisphere. A significant global rise in the number of deadly landslides and hotspots across the studied period was observed. Analysis of daily rainfall confirmed that more than half of the events were in areas exposed to the risk of extreme rainfall. The relationships established between extreme rainfall, population distribution, seasonality, and landslides provide a useful basis for efforts to model the adverse impacts of extreme rainfall due to climate change and human activities and thus contribute towards a more resilient society., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A statewide survey of questing ixodid ticks in mainland Florida was developed consistent with U.S. CDC standards to maximize the amount of epidemiologic and environmental data gathered. Survey sites were stratified by climatic zones and proportional to recognized land cover categories. A total of 560 transects on 41 sites within the state were sampled repeatedly by flagging between 2015 and 2018. Four tick species were collected; Amblyomma americanum , Amblyomma maculatum , Ixodes scapularis and Dermacentor variabilis . All species were more commonly found in northern and central regions of the state than in southern and western regions. Adult I. scapularis were active from autumn through spring and complementary to adult A. americanum and D. variabilis . Standardized survey methods help reduce sampling biases and better characterize risk from the species surveyed. However, differences in the attractiveness of collection methods for different tick species makes cross-species comparisons a continuing challenge., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The lone star ( Amblyomma americanum ), black-legged ( Ixodes scapularis ) and American dog ticks ( Dermacentor variabilis ) are species of great public health importance as they are competent vectors of several notable pathogens. While the regional distributions of these species are well characterized, more localized distribution estimates are sparse. We used records of field collected ticks and an ensemble modeling approach to predict habitat suitability for each of these species in Florida. Environmental variables capturing climatic extremes were common contributors to habitat suitability. Most frequently, annual precipitation (Bio12), mean temperature of the driest quarter (Bio9), minimum temperature of the coldest month (Bio6), and mean Normalized Difference Vegetation Index (NDVI) were included in the final models for each species. Agreement between the modeling algorithms used in this study was high and indicated the distribution of suitable habitat for all three species was reduced at lower latitudes. These findings are important for raising awareness of the potential for tick-borne pathogens in Florida.

Mutations in the ERF gene, coding for ETS2 repressor factor, a member of the ETS family of transcription factors cause a recently recognized syndromic form of craniosynostosis (CRS4) with facial dysmorphism, Chiari-1 malformation, speech and language delay, and learning difficulties and/or behavioral problems. The overall prevalence of ERF mutations in patients with syndromic craniosynostosis is around 2%, and 0.7% in clinically nonsyndromic craniosynostosis. Here, we present findings from 16 unrelated probands with ERF-related craniosynostosis, with additional data from 20 family members sharing the mutations. Most of the probands exhibited multisutural (including pan-) synostosis but a pattern involving the sagittal and lambdoid sutures (Mercedes-Benz pattern) predominated. Importantly the craniosynostosis was often postnatal in onset, insidious and progressive with subtle effects on head morphology resulting in a median age at presentation of 42 months among the probands and, in some instances, permanent visual impairment due to unsuspected raised intracranial pressure (ICP). Facial dysmorphism (exhibited by all of the probands and many of the affected relatives) took the form of orbital hypertelorism, mild exorbitism and malar hypoplasia resembling Crouzon syndrome but, importantly, a Class I occlusal relationship. Speech delay, poor gross and/or fine motor control, hyperactivity and poor concentration were common. Cranial vault surgery for raised ICP and/or Chiari-1 malformation was expected when multisutural synostosis was observed. Variable expressivity and nonpenetrance among genetically affected relatives was encountered. These observations form the most complete phenotypic and developmental profile of this recently identified craniosynostosis syndrome yet described and have important implications for surgical intervention and follow-up., (© 2019 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.)

Adipose-derived stem cells (ADSC) have come to be viewed as a ubiquitous solution for aesthetic and reconstructive problems involving loss of tissue volume and age or radiation-induced loss of tissue pliability and vascularity. As the theoretical potential of "stem cell therapy" has captured the public imagination, so the commercial potential of novel therapies is being exploited beyond scientifically sound, hypothesis-driven paradigms and in the absence of evidence establishing clinical efficacy and safety. Moreover, with variations in methods of isolation, manipulation, and reintroduction described, it is unclear how the practitioner with an interest in ADSC can harness the clinical potential in reproducible and scientifically measurable ways. This Continuing Medical Education (CME) article presents a summary of our understanding of what ADSC are, their utility within the field of aesthetic surgery, and the current and future directions for adipose stem cell research., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)