Sensory environment affects Icelandic threespine stickleback's anti-predator escape behaviour.

Human-induced changes in climate and habitats push populations to adapt to novel environments, including new sensory conditions, such as reduced visibility. We studied how colonizing newly formed glacial lakes with turbidity-induced low-visibility affects anti-predator behaviour in Icelandic threespine sticklebacks. We tested nearly 400 fish from 15 populations and four habitat types varying in visibility and colonization history in their reaction to two predator cues (mechano-visual versus olfactory) in high versus low-visibility light treatments. Fish reacted differently to the cues and were affected by lighting environment, confirming that cue modality and light levels are important for predator detection and evasion. Fish from spring-fed lakes, especially from the highlands (likely more diverged from marine fish than lowland fish), reacted fastest to mechano-visual cues and were generally most active. Highland glacial fish showed strong responses to olfactory cues and, counter to predictions from the flexible stem hypothesis, the greatest plasticity in response to light levels. This study, leveraging natural, repeated invasions of novel sensory habitats, (i) illustrates rapid changes in anti-predator behaviour that follow due to adaptation, early life experience, or both, and (ii) suggests an additional role for behavioural plasticity enabling population persistence in the face of frequent changes in environmental conditions.

Archipelago-Wide Patterns of Colonization and Speciation Among an Endemic Radiation of Galápagos Land Snails.

Newly arrived species on young or remote islands are likely to encounter less predation and competition than source populations on continental landmasses. The associated ecological release might facilitate divergence and speciation as colonizing lineages fill previously unoccupied niche space. Characterizing the sequence and timing of colonization on islands represents the first step in determining the relative contributions of geographical isolation and ecological factors in lineage diversification. Herein, we use genome-scale data to estimate timing of colonization in Naesiotus snails to the Galápagos islands from mainland South America. We test inter-island patterns of colonization and within-island radiations to understand their contribution to community assembly. Partly contradicting previously published topologies, phylogenetic reconstructions suggest that most Naesiotus species form island-specific clades, with within-island speciation dominating cladogenesis. Galápagos Naesiotus also adhere to the island progression rule, with colonization proceeding from old to young islands and within-island diversification occurring earlier on older islands. Our work provides a framework for evaluating the contribution of colonization and in situ speciation to the diversity of other Galápagos lineages.

Local control after brain-directed radiation in patients with cystic versus solid brain metastases.

PURPOSE: Brain metastases can be radiographically cystic or solid. Cystic metastases are associated with a greater intracranial disease burden and poorer oncologic outcomes, but the impact of cystic versus solid appearance on local control after radiation remains unknown. We investigated whether cystic versus solid nature is predictive of local control after management with stereotactic or whole brain radiation (WBRT) and whether the radiation modality utilized is an effect modifier. METHODS: We identified 859 patients with 2211 newly-diagnosed brain metastases managed with upfront stereotactic radiation or WBRT without preceding resection/aspiration at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015. Multivariable Cox regression with an interaction term and sandwich covariance matrix was used to quantify local failure. RESULTS: Cystic lesions were more likely to recur than solid ones when managed with stereotactic radiation (HR 2.33, 95% CI 1.32-4.10, p = 0.004) but not WBRT (HR 0.92, 95% CI 0.62-1.36, p = 0.67), p-interaction = 0.007. 1 year local control rates for cystic versus solid metastases treated with stereotactic radiation were 75% versus 88%, respectively; estimates with WBRT were 76% versus 76%, respectively. However, no significant differences were noted between the two cohorts in post-radiation outcomes including all-cause mortality and neurologic death (p > 0.05). CONCLUSIONS: Among patients with brain metastases, stereotactic radiation yields improved local control and less morbidity than WBRT, and consequently for many patients the cystic versus solid designation does not impact treatment selection. However, our results suggest that in patients with a large number of cystic brain metastases, a lower threshold to consider WBRT, as opposed to stereotactic radiation, should be employed. If our results can be confirmed, further investigation into the underlying mechanism(s) would be warranted.

Rapid phenotypic evolution following shifts in life cycle complexity.

Life cycle strategies have evolved extensively throughout the history of metazoans. The expression of disparate life stages within a single ontogeny can present conflicts to trait evolution, and therefore may have played a major role in shaping metazoan forms. However, few studies have examined the consequences of adding or subtracting life stages on patterns of trait evolution. By analysing trait evolution in a clade of closely related salamander lineages we show that shifts in the number of life cycle stages are associated with rapid phenotypic evolution. Specifically, salamanders with an aquatic-only (paedomorphic) life cycle have frequently added vertebrae to their trunk skeleton compared with closely related lineages with a complex aquatic-to-terrestrial (biphasic) life cycle. The rate of vertebral column evolution is also substantially lower in biphasic lineages, which may reflect the functional compromise of a complex cycle. This study demonstrates that the consequences of life cycle evolution can be detected at very fine scales of divergence. Rapid evolutionary responses can result from shifts in selective regimes following changes in life cycle complexity.

Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide.

An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69µM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure-lowering agent for use in functional foods.

The Effects of 405-nm Visible Light on the Survival of Campylobacter on Chicken Skin and Stainless Steel.

Campylobacter spp. are foodborne pathogens responsible for a significant portion of human cases of bacterial-mediated gastrointestinal disease. A primary method for the introduction of Campylobacter into the food supply is through poultry products. Reducing the number of Campylobacter on poultry products may reduce the incidence of human disease. Research has been conducted on the use of light to inactivate Campylobacter on poultry products and processing environments. More recently, the use of high intensity visible 405-nm light has been proposed for the elimination of pathogenic bacteria. This study investigated the ability of 405-nm light to reduce Campylobacter jejuni and Campylobacter coli in poultry products. Campylobacter in chicken exudate were placed onto chicken skin or food-grade stainless steel before treatment with 405-nm light. A range of 405-nm light doses were applied to cocktails of six C. jejuni or six C. coli strains in exudate at 10°C to minimize thermal effects. Little difference was observed between inactivation of C. jejuni and C. coli on poultry skin with only minor average reductions of 1.7 logs and 2.1 logs, respectively, at the maximal dose of 184-186 J/cm(2). More noticeable differences were observed when the samples were placed on stainless steel and treated with a dose of 89 J/cm(2), producing an average reduction of 3.0 logs for C. coli but only 1.1 logs for C. jejuni. The maximal dose (181-183 J/cm(2)) applied to Campylobacter on stainless steel produced significant (p ≤ 0.05) reductions for C. jejuni and C. coli of 4.9 logs and 5.1 logs, respectively. However, significant 405-nm-mediated reductions in Campylobacter numbers required exposure times to achieve necessary dose levels that might be impractical under processing conditions. In addition, the most potent exposure times likely produced secondary thermal effects by raising sample surface temperatures above 48°C.

Biogeography and evolution of a widespread Central American lizard species complex: Norops humilis, (Squamata: Dactyloidae).

BACKGROUND: Caribbean anole lizards (Dactyloidae) have frequently been used as models to study questions regarding biogeography and adaptive radiations, but the evolutionary history of Central American anoles (particularly those of the genus Norops) has not been well studied. Previous work has hypothesized a north-to-south dispersal pattern of Central American Norops, but no studies have examined dispersal within any Norops lineages. Here we test two major hypotheses for the dispersal of the N. humilis/quaggulus complex (defined herein, forming a subset within Savage and Guyer's N. humilis group). RESULTS: Specimens of the N. humilis group were collected in Central America, from eastern Mexico to the Canal Zone of Panama. Major nodes were dated for comparison to the geologic history of Central America, and ancestral ranges were estimated for the N. humilis/quaggulus complex to test hypothesized dispersal patterns. These lineages displayed a northward dispersal pattern. We also demonstrate that the N. humilis/quaggulus complex consists of a series of highly differentiated mitochondrial lineages, with more conserved nuclear evolution. The paraphyly of the N. humilis species group is confirmed. A spatial analysis of molecular variance suggests that current populations are genetically distinct from one another, with limited mitochondrial gene flow occurring among sites. CONCLUSIONS: The observed south-to-north colonization route within the Norops humilis/quaggulus complex represents the first evidence of a Norops lineage colonizing in a south-to-north pattern, (opposite to the previously held hypothesis for mainland Norops). One previously described taxon (N. quaggulus) was nested within N. humilis, demonstrating the paraphyly of this species; while our analyses also reject the monophyly of the Norops humilis species group (sensu Savage and Guyer), with N. tropidonotus, N. uniformis, and N. marsupialis being distantly related to/highly divergent from the N. humilis/quaggulus complex. Our work sheds light on mainland anole biogeography and past dispersal events, providing a pattern to test against other groups of mainland anoles.

Salmonella and Escherichia coli O157:H7 survival in soil and translocation into leeks (Allium porrum) as influenced by an arbuscular mycorrhizal fungus (Glomus intraradices).

A study was conducted to determine the influence of arbuscular mycorrhizal (AM) fungi on Salmonella and enterohemorrhagic Escherichia coli O157:H7 (EHEC) in autoclaved soil and translocation into leek plants. Six-week-old leek plants (with [Myc+] or without [Myc-] AM fungi) were inoculated with composite suspensions of Salmonella or EHEC at ca. 8.2 log CFU/plant into soil. Soil, root, and shoot samples were analyzed for pathogens on days 1, 8, 15, and 22 postinoculation. Initial populations (day 1) were ca. 3.1 and 2.1 log CFU/root, ca. 2.0 and 1.5 log CFU/shoot, and ca. 5.5 and 5.1 CFU/g of soil for Salmonella and EHEC, respectively. Enrichments indicated that at days 8 and 22, only 31% of root samples were positive for EHEC, versus 73% positive for Salmonella. The mean Salmonella level in soil was 3.4 log CFU/g at day 22, while EHEC populations dropped to ≤ 0.75 log CFU/g by day 15. Overall, Salmonella survived in a greater number of shoot, root, and soil samples, compared with the survival of EHEC. EHEC was not present in Myc- shoots after day 8 (0/16 samples positive); however, EHEC persisted in higher numbers (P = 0.05) in Myc+ shoots (4/16 positive) at days 15 and 22. Salmonella, likewise, survived in statistically higher numbers of Myc+ shoot samples (8/8) at day 8, compared with survival in Myc- shoots (i.e., only 4/8). These results suggest that AM fungi may potentially enhance the survival of E. coli O157:H7 and Salmonella in the stems of growing leek plants.

Growth of a pYV-bearing Yersinia pestis KIM5 in retail raw ground pork.

Yersinia pestis can cause oropharyngeal plague as a result of consumption or handling of meat from infected animals. Thus, food naturally or intentionally contaminated can have a role in the dissemination of oropharyngeal plague. The growth of a conditionally virulent pYV-bearing rifampicin-resistant Y. pestis KIM5 (rif-Y. pestis KIM5) in retail raw ground pork (RGP) was studied at temperatures ranging from 4 to 30°C. At 4°C, rif-Y. pestis KIM5 did not grow but survived. In RGP, rif-Y. pestis KIM5 grew at refrigerated temperatures of 10 and 15°C with growth rates of 0.05 and 0.16 log(10) colony-forming units (CFU)/h. The growth rates at abusive temperatures of 20, 25, and 30°C were 0.26, 0.30, and 0.77 log(10) CFU/h. The growth rate was increased 15.4-fold with the increase of storage temperatures from 10°C to 30°C. The maximum population density ranged from 6.76 to 8.66 log(10) CFU/g. Furthermore, there was no detectable loss of pYV in surviving rif-Y. pestis KIM5 at any of the temperatures tested in retail RGP. This suggests that under these conditions, Y. pestis could cause oropharyngeal plague if the meat was not properly cooked. The individual infected by Y. pestis in food is a potential reservoir who can infect others, leading to outbreaks of plague.

Peroxide resistance in Escherichia coli serotype O157 : H7 biofilms is regulated by both RpoS-dependent and -independent mechanisms.

In many Escherichia coli serotype O157 : H7 strains, defences against peroxide damage include the peroxiredoxin AhpCF and three catalases: KatG (catalase/peroxidase), KatE (catalase) and the plasmid-encoded KatP (catalase/peroxidase). AhpC and KatG basal expression is maintained by RpoS, and AhpC, KatG and KatP are all induced by OxyR/σ(70) in exponential phase. KatE is regulated by RpoS during stationary growth and is independent of OxyR. In a previous study we used mutant strains of ATCC 43895 (EDL933) with deletions of katG, ahpC, katE and katP in all possible combinations to characterize peroxide resistance during both exponential and 18-24 h growth in Luria-Bertani broth at 37 °C. In this study, we used triple deletion strains that isolated each catalase/peroxidase gene to investigate their role in the peroxide resistance of biofilm-forming variant 43895OR in 48 and 72 h biofilms. We also used quantitative real-time reverse transcriptase PCR and translational lacZ fusions to study gene expression. Peroxide resistance was greater (P<0.05) in biofilm cells than in planktonic cells, and full resistance required rpoS but not oxyR. In 72 h biofilms, katG and katE were the major protective genes. katG, ahpC and katE peroxide protection had both rpoS-dependent and rpoS-independent components, but katP protection was independent of rpoS. H(2)O(2) challenge induced (P<0.05) katG, ahpC and katP expression in biofilm cells, suggesting that peroxide induction of the OxyR-dependent resistance genes may contribute to the RpoS-independent protection in Shiga toxin-producing E. coli biofilms.

Multidisciplinary management of early-stage rectal cancer.

Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer.

Survival Prediction After Neurosurgical Resection of Brain Metastases: A Machine Learning Approach.

BACKGROUND: Current prognostic models for brain metastases (BMs) have been constructed and validated almost entirely with data from patients receiving up-front radiotherapy, leaving uncertainty about surgical patients. OBJECTIVE: To build and validate a model predicting 6-month survival after BM resection using different machine learning algorithms. METHODS: An institutional database of 1062 patients who underwent resection for BM was split into an 80:20 training and testing set. Seven different machine learning algorithms were trained and assessed for performance; an established prognostic model for patients with BM undergoing radiotherapy, the diagnosis-specific graded prognostic assessment, was also evaluated. Model performance was assessed using area under the curve (AUC) and calibration. RESULTS: The logistic regression showed the best performance with an AUC of 0.71 in the hold-out test set, a calibration slope of 0.76, and a calibration intercept of 0.03. The diagnosis-specific graded prognostic assessment had an AUC of 0.66. Patients were stratified into regular-risk, high-risk and very high-risk groups for death at 6 months; these strata strongly predicted both 6-month and longitudinal overall survival ( P < .0005). The model was implemented into a web application that can be accessed through http://brainmets.morethanml.com . CONCLUSION: We developed and internally validated a prediction model that accurately predicts 6-month survival after neurosurgical resection for BM and allows for meaningful risk stratification. Future efforts should focus on external validation of our model.

Predicting leptomeningeal disease spread after resection of brain metastases using machine learning.

OBJECTIVE: The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of individual studies investigating LMD after surgery for BMs and its risk factors have been limited, ranging from 200 to 400 patients at risk for LMD, which only allows the use of conventional biostatistics. Here, the authors used machine learning techniques to enhance LMD prediction in a cohort of surgically treated BMs. METHODS: A conditional survival forest, a Cox proportional hazards model, an extreme gradient boosting (XGBoost) classifier, an extra trees classifier, and logistic regression were trained. A synthetic minority oversampling technique (SMOTE) was used to train the models and handle the inherent class imbalance. Patients were divided into an 80:20 training and test set. Fivefold cross-validation was used on the training set for hyperparameter optimization. Patients eligible for study inclusion were adults who had consecutively undergone neurosurgical BM treatment, had been admitted to Brigham and Women's Hospital from January 2007 through December 2019, and had a minimum of 1 month of follow-up after neurosurgical treatment. RESULTS: A total of 1054 surgically treated BM patients were included in this analysis. LMD occurred in 168 patients (15.9%) at a median of 7.05 months after BM diagnosis. The discrimination of LMD occurrence was optimal using an XGboost algorithm (area under the curve = 0.83), and the time to LMD was prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76). The most important feature for both LMD classification and regression was the BM proximity to the CSF space, followed by a cerebellar BM location. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest risk factors for both LMD occurrence and time to LMD. CONCLUSIONS: The outcomes of LMD patients in the BM population are predictable using SMOTE and machine learning. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest LMD risk factors.

Neurosurgical resection for locally recurrent brain metastasis.

BACKGROUND: In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population. METHODS: Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM). RESULTS: Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with >24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (P < 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, P < 0.05) but similar ICC (hazard ratio 1.11 in both groups, P > 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes. CONCLUSIONS: In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

Programmed Death Receptor Ligand One Expression May Independently Predict Survival in Patients With Non-Small Cell Lung Carcinoma Brain Metastases Receiving Immunotherapy.

PURPOSE: Programmed death receptor ligand 1 (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. METHODS AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM with available PD-L1 expression were identified. PD-L1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR, 0.86 per 10% expression; 95% CI, 0.77-0.98; P = .02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR, 0.54; 95% CI, 0.26-1.14; P = .11). CONCLUSIONS: In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-graded prognostic assessment. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.

Academic ecosystems must evolve to support a sustainable postdoc workforce.

The postdoctoral workforce comprises a growing proportion of the science, technology, engineering and mathematics (STEM) community, and plays a vital role in advancing science. Postdoc professional development, however, remains rooted in outdated realities. We propose enhancements to postdoc-centred policies and practices to better align this career stage with contemporary job markets and work life. By facilitating productivity, wellness and career advancement, the proposed changes will benefit all stakeholders in postdoc success-including research teams, institutions, professional societies and the scientific community as a whole. To catalyse reform, we outline recommendations for (1) skills-based training tailored to the current career landscape, and (2) supportive policies and tools outlined in postdoc handbooks. We also invite the ecology and evolution community to lead further progressive reform.

Neurosurgical Resection and Stereotactic Radiation Versus Stereotactic Radiation Alone in Patients with a Single or Solitary Brain Metastasis.

BACKGROUND: Brain metastases commonly manifest in patients with cancer, with ∼20%-50% presenting with 1 intracranial lesion. Among patients with 1, small brain metastasis and controlled or absent extracranial disease, it remains unclear whether aggressive intracranial management using neurosurgical resection plus cavity stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) rather than SRS/SRT alone is beneficial. In patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size, we evaluated the effect of surgery plus SRS/SRT compared with SRS/SRT on oncologic outcomes, including overall survival. METHODS: We retrospectively identified 86 patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size who had been treated from 2000 to 2015 at our institution. We examined differences in the rates of local and distant failure, use of salvage treatment, and other oncologic outcomes, including all-cause mortality. RESULTS: The baseline characteristics were similar between the 2 cohorts. The median follow-up period for the surviving patients was 38 months. On multivariable analysis, surgical resection plus cavity SRS/SRT was associated with a lower risk of all-cause mortality (hazard ratio, 0.44; 95% confidence interval, 0.19-1.00; P = 0.05) compared with SRS/SRT alone. The 1- and 2-year rates of overall survival were 100% and 88% versus 74% and 52% for surgery plus cavity SRS/SRT versus SRS/SRT alone, respectively. CONCLUSIONS: Aggressive, local therapy, including neurosurgical resection, might benefit patients with 1 brain metastasis in the context of controlled or absent systemic disease, even if the lesion in question is small. Further studies are needed to evaluate these associations.

Transfer coefficient models for escherichia coli O157:H7 on contacts between beef tissue and high-density polyethylene surfaces.

Risk studies have identified cross-contamination during beef fabrication as a knowledge gap, particularly as to how and at what levels Escherichia coli O157:H7 transfers among meat and cutting board (or equipment) surfaces. The objectives of this study were to determine and model transfer coefficients (TCs) between E. coli O157:H7 on beef tissue and high-density polyethylene (HDPE) cutting board surfaces. Four different transfer scenarios were evaluated: (i) HDPE board to agar, (ii) beef tissue to agar, (iii) HDPE board to beef tissue to agar, and (iv) beef tissue to HDPE board to agar. Also, the following factors were studied for each transfer scenario: two HDPE surface roughness levels (rough and smooth), two beef tissues (fat and fascia), and two conditions of the initial beef tissue inoculation with E. coli O157:H7 (wet and dry surfaces), for a total of 24 treatments. The TCs were calculated as a function of the plated inoculum and of the cells recovered from the first contact. When the treatments were compared, all of the variables evaluated interacted significantly in determining the TC. An overall TC-per-treatment model did not adequately represent the reduction of the cells on the original surface after each contact and the interaction of the factors studied. However, an exponential model was developed that explained the experimental data for all treatments and represented the recontamination of the surfaces with E. coli O157:H7. The parameters for the exponential model for cross-contamination with E. coli O157:H7 between beef tissue and HDPE surfaces were determined, allowing for the use of the resulting model in quantitative microbial risk assessment.

Acute gastrointestinal toxicity and bowel bag dose-volume parameters for preoperative radiation therapy for retroperitoneal sarcoma.

PURPOSE: Acute gastrointestinal (GI) toxicity has been studied in GI and gynecological (GYN) cancers, with volume receiving 15 Gy (V15) <830 mL, V25 <650 mL, and V45 <195 mL identified as dose constraints for the peritoneal space (bowel bag [BB]). There are no reported constraints derived from retroperitoneal sarcoma (RPS), and prospective trials for RPS have adopted some of the GI and GYN constraints. This study quantified GI toxicity during preoperative radiation therapy (RT) for RPS, assessed toxicity using published constraints, and evaluated predictors for toxicity. METHODS AND MATERIALS: From 2003 to 2013, 56 patients with RPS underwent preoperative RT at 2 institutions. Toxicity was scored using Radiation Therapy Oncology Group criteria for upper and lower acute GI toxicity. BB was contoured on planning computed tomography scans per Radiation Therapy Oncology Group atlas guidelines with review by a radiologist. Relationships among toxicity, clinical factors, and BB dose were analyzed. RESULTS: Three patients (5%) developed grade ≥3 acute GI toxicity: 2 grade 3 toxicities (anorexia and nausea) and 1 grade 5 toxicity (tumor-bowel fistula). Thirty-six patients (64%) had grade 2 toxicity (nausea, 55%; diarrhea, 23%; pain, 20%). Tumor size was the only significant clinical predictor of grade ≥2 acute GI toxicity. Larger mean BB volumes predicted for grade ≥2 toxicity (P = .001). On receiver operating characteristics analysis, V30 was the best discriminator for toxicity (P = .0001). Median BB V15 was 1375 mL; 75% of patients had V15 ≥830 mL. Median V25 was 1083 mL; 68% had V25 ≥650 mL. Median V45 was 575 mL; 82% had V45 ≥195 mL. V25 ≥650 mL was significantly associated with grade ≥2 toxicity (P = .01). CONCLUSIONS: Among patients treated with preoperative RT for RPS, significant acute GI toxicity was very low despite BB dose exceeding established constraints for most cases. Acceptable dose constraints for RPS may be higher than those for GI or GYN cancers. Further assessment of dose-volume constraints for RPS is needed.