The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients ...at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
In the management of orbital disorders and defects, minimally invasive surgical approaches have become increasingly efficient for their reduction of operative trauma and access without compromise of ...therapeutic benefit or diagnostic yield. Various approaches have focused on bone- and canthal-sparing techniques and concealed and small skin incisions. We review the current state of knowledge of procedures to enter the orbit via the conjunctiva.
Any quadrant of the orbit can be accessed via the conjunctiva. Surgical incisions involve the orbital palpebral, forniceal, and bulbar conjunctiva. According to the location, nature, and size of the lesion, the transconjunctival orbitotomy can be used as a single procedure, in combination with a caruncular approach or as an adjunct in a multidisciplinary procedure for lesions extending deep into or outside the orbit. The working space and field of operating view can be expanded by releasing the horizontal tension of the eyelid with a lateral cantholysis, lateral paracanthal blepharotomy, or medial lid split procedure. Complications related to the conjunctival incision are reduced to dry eye disease.
In Shark Bay, Western Australia, male bottlenose dolphins form a complex nested alliance hierarchy. At the first level, pairs or trios of unrelated males cooperate to herd individual females. ...Multiple first-order alliances cooperate in teams (second-order alliances) in the pursuit and defence of females, and multiple teams also work together (third-order alliances). Yet it remains unknown how dolphins classify these nested alliance relationships. We use 30 years of behavioural data combined with 40 contemporary sound playback experiments to 14 allied males, recording responses with drone-mounted video and a hydrophone array. We show that males form a first-person social concept of cooperative team membership at the second-order alliance level, independently of first-order alliance history and current relationship strength across all three alliance levels. Such associative concepts develop through experience and likely played an important role in the cooperative behaviour of early humans. These results provide evidence that cooperation-based concepts are not unique to humans, occurring in other animal societies with extensive cooperation between non-kin.
Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen ...interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model host
with one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen's growth inside the host, its competitiveness towards other pathogens and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should first target the most virulent species to reduce host morbidity, a prediction we validated experimentally.
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients ...at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3−6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Benchmark dose (BMD) modeling is now the state of the science for determining the point of departure for risk assessment. Key advantages include the fact that the modeling takes account of all of the ...data for a particular effect from a particular experiment, increased consistency, and better accounting for statistical uncertainties. Despite these strong advantages, disagreements remain as to several specific aspects of the modeling, including differences in the recommendations of the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA). Differences exist in the choice of the benchmark response (BMR) for continuous data, the use of unrestricted models, and the mathematical models used; these can lead to differences in the final BMDL. It is important to take confidence in the model into account in choosing the BMDL, rather than simply choosing the lowest value. The field is moving in the direction of model averaging, which will avoid many of the challenges of choosing a single best model when the underlying biology does not suggest one, but additional research would be useful into methods of incorporating biological considerations into the weights used in the averaging. Additional research is also needed regarding the interplay between the BMR and the UF to ensure appropriate use for studies supporting a lower BMR than default values, such as for epidemiology data. Addressing these issues will aid in harmonizing methods and moving the field of risk assessment forward.
PURPOSE OF REVIEWPeriocular rehabilitation of the patient with a facial nerve palsy has evolved over time. Although protection of the ocular surface is paramount, application of disfiguring ...tarsorrhaphies should be utilized only in special situations. The purpose of this review is to discuss current surgical and medical strategies in treatment of the periocular area in patients with facial nerve palsy to give maximal functional and cosmetic results.
RECENT FINDINGSUpper lid lagophthalmos is preferentially treated with upper eyelid weights. Platinum has distinct advantages over gold. A supratarsal position of the upper lid weight is preferred over a pretarsal location. Lower lid malposition should be treated as a retraction, rather than an ectropion. Recalcitrant ocular surface disease can be effectively managed with a scleral lens. Tearing in the patient with a facial nerve palsy is often multifactorial; small lumen Jones tubes and botulinum toxin injection to the lacrimal gland should be considered to treat epiphora in these patients.
SUMMARYA facial nerve palsy can be devastating for patients from both a functional and cosmetic perspective. Although seismic shifts in treatment of the periocular subunit have not occurred, there are a number of small, yet significant, changes in treatment that should be adopted in taking care of these patients.
Efforts to understand human social evolution rely largely on comparisons with nonhuman primates. However, a population of bottlenose dolphins in Shark Bay, Western Australia, combines a ...chimpanzee-like fission-fusion grouping pattern, mating system, and life history with the only nonhuman example of strategic multilevel male alliances. Unrelated male dolphins form three alliance levels, or “orders”, in competition over females: both within-group alliances (i.e., first- and second-order) and between-group alliances (third-order), based on cooperation between two or more second-order alliances against other groups. Both sexes navigate an open society with a continuous mosaic of overlapping home ranges. Here, we use comprehensive association and consortship data to examine fine-scale alliance relationships among 121 adult males. This analysis reveals the largest nonhuman alliance network known, with highly differentiated relationships among individuals. Each male is connected, directly or indirectly, to every other male, including direct connections with adult males outside of their three-level alliance network. We further show that the duration with which males consort females is dependent upon being well connected with third-order allies, independently of the effect of their second-order alliance connections, i.e., alliances between groups increase access to a contested resource, thereby increasing reproductive success. Models of human social evolution traditionally link intergroup alliances to other divergent human traits, such as pair bonds, but our study reveals that intergroup male alliances can arise directly from a chimpanzee-like, promiscuous mating system without one-male units, pair bonds, or male parental care.
To use time-driven, activity-based costing (TDABC) methodology to investigate drivers of cost variation and to elucidate preoperative and intraoperative factors associated with increased cost of ...outpatient arthroscopic hip labral repair.
A retrospective analysis of data from January 2020 to October 2021 was performed. Patients undergoing primary hip arthroscopy for labral repair in the outpatient setting were included. Indexed TDABC data from Avant-garde Health’s analytics platform were used to represent cost-of-care breakdowns. Patients in the top decile of cost were defined as high cost, and cost category variance was determined as a percent increase between high and low cost. Analyses tested for associations between preoperative and perioperative factors with total cost. Surgical procedures performed concomitantly to labral repair were included in subanalyses.
Data from 151 patients were analyzed. Consumables made up 61% of total outpatient cost with surgical personnel costs (30%) being the second largest category. The average total cost was 19% higher for patients in the top decile of cost compared to the remainder of the cohort. Factors contributing to this difference were implants (36% higher), surgical personnel (20% higher), and operating room (OR) consumables (15% higher). Multivariate linear regression modeling indicated that OR time (Standardized β = 0.504; P < .001) and anchor quantity (standardized β = 0.443; P < .001) were significant predictors of increased cost. Femoroplasty (Unstandardized β = 15.274; P = .010), chondroplasty (Unstandardized β = 8.860; P = .009), excision of os acetabuli (unstandardized β = 13.619; P = .041), and trochanteric bursectomy (Unstandardized β = 21.176; P = .009) were also all independently associated with increasing operating time.
TDABC analysis showed that OR consumables and implants were the largest drivers of cost for the procedure. OR time was also shown to be a significant predictor of increased costs.
Level IV, economic analysis.
Quorum sensing (QS) is a cell-cell communication system found in many bacterial species, commonly controlling secreted co-operative traits, including extracellular digestive enzymes. We show that the ...canonical QS regulatory architecture allows bacteria to sense the genotypic composition of high-density populations, and limit co-operative investments to social environments enriched for co-operators. Using high-density populations of the opportunistic pathogen Pseudomonas aeruginosa we map per-capita signal and co-operative enzyme investment in the wild type as a function of the frequency of non-responder cheats. We demonstrate mathematically and experimentally that the observed response rule of 'co-operate when surrounded by co-operators' allows bacteria to match their investment in co-operation to the composition of the group, therefore allowing the maintenance of co-operation at lower levels of population structuring (that is, lower relatedness). Similar behavioural responses have been described in vertebrates under the banner of 'generalised reciprocity'. Our results suggest that mechanisms of reciprocity are not confined to taxa with advanced cognition, and can be implemented at the cellular level via positive feedback circuits.
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