The pharmacokinetics and pharmacodynamics of fentanyl administered via transdermal patch in horses.

Introduction: Understanding the pharmacokinetics and pharmacodynamics of fentanyl in horses is crucial for optimizing pain management strategies in veterinary medicine. Methods: Six adult horses were enrolled in a randomized crossover design. Treatments included: placebo, two 100 mcg/h patches (LDF), four 100 mcg/h patches (MDF), and six 100 mcg/h patches (HDF). Patches were in place for 72 h. Blood was obtained for fentanyl plasma concentration determination, thermal threshold, mechanical threshold, heart rate, respiratory rate, and rectal temperature were obtained prior patch placement and at multiple time points following patch placement for the following 96 h. Fentanyl plasma concentration was determined using LC-MS/MS. Data were analyzed using a generalized mixed effects model. Results: Mean (range) maximum plasma concentration (Cmax), time to Cmax, and area under the curve extrapolated to infinity were 1.39 (0.82-1.82), 2.64 (1.21-4.42), 4.11 (2.78-7.12) ng/ml, 12.7 (8.0-16.0), 12.7 (8.0-16.0), 12 (8.0-16.0) h, 42.37 (27.59-55.56), 77.24 (45.62-115.06), 120.34 (100.66-150.55) h ng/ml for LDF, MDF, and HDF, respectively. There was no significant effect of treatment or time on thermal threshold, mechanical threshold, respiratory rate, or temperature (p > 0.063). There was no significant effect of treatment on heart rate (p = 0.364). There was a significant effect of time (p = 0.003) on heart rate with overall heart rates being less than baseline at 64 h. Conclusions: Fentanyl administered via transdermal patch is well absorbed and well tolerated but does not result in an anti-nociceptive effect as measured by thermal and mechanical threshold at the doses studied.

Best practice recommendations for the management of anxiety during the pegvaliase journey.

BACKGROUND: Pegvaliase, an enzyme substitution therapy, is a treatment option for phenylketonuria (PKU). Due to the neuropathophysiology and disease burden of PKU, individuals can experience baseline anxiety unrelated to pegvaliase therapy. In addition, there are aspects of pegvaliase therapy that may be anxiety-inducing for those considering or receiving treatment. The aim of this manuscript is to present best practice recommendations for the identification and management of anxiety symptoms that can occur along the pegvaliase journey. METHODS: A modified Delphi approach was used to seek consensus among a multidisciplinary panel of experts. To this end, an in-person meeting was held that was preceded by a medical specialist- and patient-specific survey to develop preliminary recommendations on ways to address anxiety along the pegvaliase journey. After the meeting, an additional survey was conducted to rank the proposed solutions and mitigation strategies from which a set of recommendations was developed. All recommendations were voted on with the aim of consensus generation, defined as achieving ≥75% agreement among experts. RESULTS: The panel reached consensus on a total of 28 best practice recommendations for the management of anxiety during the pre-treatment, induction and titration, early maintenance (pre-efficacy), and late maintenance (post-efficacy) stages. The recommendations offer strategies to identify and address the most common causes of pegvaliase-related anxiety, including self-injection, side effects, the titration schedule, prescribed dietary changes, and variable time to efficacy. Overall, managing anxiety in those considering or receiving pegvaliase involves patient-centered communication, shared decision-making, and personalized treatment plans. CONCLUSIONS: The best practice recommendations described herein can guide healthcare providers in proactively addressing anxiety during the different stages of pegvaliase treatment, and support providers with initiating and managing pegvaliase in individuals who may experience baseline and treatment-related anxiety.

Morphological diversity of cancer cells predicts prognosis across tumor types.

BACKGROUND: Intratumor heterogeneity drives disease progression and treatment resistance, which can lead to poor patient outcomes. Here, we present a computational approach for quantification of cancer cell diversity in routine hematoxylin-eosin-stained histopathology images. METHODS: We analyzed publicly available digitized whole-slide hematoxylin-eosin images for 2000 patients. Four tumor types were included: lung, head and neck, colon, and rectal cancers, representing major histology subtypes (adenocarcinomas and squamous cell carcinomas). We performed single-cell analysis on hematoxylin-eosin images and trained a deep convolutional autoencoder to automatically learn feature representations of individual cancer nuclei. We then computed features of intranuclear variability and internuclear diversity to quantify tumor heterogeneity. Finally, we used these features to build a machine-learning model to predict patient prognosis. RESULTS: A total of 68 million cancer cells were segmented and analyzed for nuclear image features. We discovered multiple morphological subtypes of cancer cells (range = 15-20) that co-exist within the same tumor, each with distinct phenotypic characteristics. Moreover, we showed that a higher morphological diversity is associated with chromosome instability and genomic aneuploidy. A machine-learning model based on morphological diversity demonstrated independent prognostic values across tumor types (hazard ratio range = 1.62-3.23, P < .035) in validation cohorts and further improved prognostication when combined with clinical risk factors. CONCLUSIONS: Our study provides a practical approach for quantifying intratumor heterogeneity based on routine histopathology images. The cancer cell diversity score can be used to refine risk stratification and inform personalized treatment strategies.

Parosteal Lipoma Overlying an Osteochondroma of the Hyoid Bone: A Case Report and Literature Review.

Parosteal lipomas and osteochondromas of the head and neck are uncommon benign tumors, constituting a small fraction of lipoma and bone tumor cases. We present a unique case of a 66-year-old male with a parosteal lipoma overlying an osteochondroma in the anterior midline neck, causing dysphagia. Surgical excision confirmed the diagnosis, and a literature review revealed similar cases predominantly adjacent to the mandible or calvaria. This case emphasizes the need to have parosteal lipoma and osteochondroma on the differential diagnosis for patients presenting with a firm mass of the central neck, especially with a history of trauma. Laryngoscope, 2023.

Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC.

The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, NRF2 signaling intensity positively correlated with NRF2-activating mutations and with SOX2 protein expression. Protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus infection status. CDKN2A (p16) protein expression positively correlated with the human papilloma virus oncogenic E7 protein and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or formalin-fixed paraffin-embedded archived tissues in under 90 min.

Post-anesthetic CPS and EQUUS-FAP scores in surgical and non-surgical equine patients: an observational study.

Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs. Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures. Study design: Clinical observational study. Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected. Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2. Main limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results. Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively.

Galectin-1 Mediates Chronic STING Activation in Tumors to Promote Metastasis through MDSC Recruitment.

The immune system plays a crucial role in the regulation of metastasis. Tumor cells systemically change immune functions to facilitate metastatic progression. Through this study, we deciphered how tumoral galectin-1 (Gal1) expression shapes the systemic immune environment to promote metastasis in head and neck cancer (HNC). In multiple preclinical models of HNC and lung cancer in immunogenic mice, Gal1 fostered the establishment of a premetastatic niche through polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), which altered the local microenvironment to support metastatic spread. RNA sequencing of MDSCs from premetastatic lungs in these models demonstrated the role of PMN-MDSCs in collagen and extracellular matrix remodeling in the premetastatic compartment. Gal1 promoted MDSC accumulation in the premetastatic niche through the NF-κB signaling axis, triggering enhanced CXCL2-mediated MDSC migration. Mechanistically, Gal1 sustained NF-κB activation in tumor cells by enhancing stimulator of interferon gene (STING) protein stability, leading to prolonged inflammation-driven MDSC expansion. These findings suggest an unexpected protumoral role of STING activation in metastatic progression and establish Gal1 as an endogenous-positive regulator of STING in advanced-stage cancers. SIGNIFICANCE: Galectin-1 increases STING stability in cancer cells that activates NF-κB signaling and CXCL2 expression to promote MDSC trafficking, which stimulates the generation of a premetastatic niche and facilitates metastatic progression.

NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells.

Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found that mutations in NFE2L2, which encodes Nrf2, are associated with a significantly higher rate of LRF in patients with oral cavity cancer treated with surgery and adjuvant (chemo)radiotherapy but not in those treated with surgery alone. Somatic mutation of NFE2L2 led to Nrf2 activation and radioresistance in HNSCC cells. Tumors harboring mutant Nrf2E79Q were substantially more radioresistant than tumors with wild-type Nrf2 in immunocompetent mice, whereas the difference was diminished in immunocompromised mice. Nrf2E79Q enhanced radioresistance through increased recruitment of intratumoral polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and reduction of M1-polarized macrophages. Treatment with the glutaminase inhibitor CB-839 overcame the radioresistance induced by Nrf2E79Q or Nrf2E79K. RT increased expression of PMN-MDSC-attracting chemokines, including CXCL1, CXLC3, and CSF3, in Nrf2E79Q-expressing tumors via the TLR4, which could be reversed by CB-839. This study provides insights into the impact of NFE2L2 mutations on radioresistance and suggests that CB-839 can increase radiosensitivity by switching intratumoral myeloid cells to an antitumor phenotype, supporting clinical testing of CB-839 with RT in HNSCC with NFE2L2 mutations. SIGNIFICANCE: NFE2L2 mutations are predictive biomarkers of radioresistance in head and neck cancer and confer sensitivity to glutaminase inhibitors to overcome radioresistance.

Detection of cryptogenic malignancies from metagenomic whole genome sequencing of body fluids.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of body fluids is an emerging approach to identify occult pathogens in undiagnosed patients. We hypothesized that metagenomic testing can be simultaneously used to detect malignant neoplasms in addition to infectious pathogens. METHODS: From two independent studies (n = 205), we used human data generated from a metagenomic sequencing pipeline to simultaneously screen for malignancies by copy number variation (CNV) detection. In the first case-control study, we analyzed body fluid samples (n = 124) from patients with a clinical diagnosis of either malignancy (positive cases, n = 65) or infection (negative controls, n = 59). In a second verification cohort, we analyzed a series of consecutive cases (n = 81) sent to cytology for malignancy workup that included malignant positives (n = 32), negatives (n = 18), or cases with an unclear gold standard (n = 31). RESULTS: The overall CNV test sensitivity across all studies was 87% (55 of 63) in patients with malignancies confirmed by conventional cytology and/or flow cytometry testing and 68% (23 of 34) in patients who were ultimately diagnosed with cancer but negative by conventional testing. Specificity was 100% (95% CI 95-100%) with no false positives detected in 77 negative controls. In one example, a patient hospitalized with an unknown pulmonary illness had non-diagnostic lung biopsies, while CNVs implicating a malignancy were detectable from bronchoalveolar fluid. CONCLUSIONS: Metagenomic sequencing of body fluids can be used to identify undetected malignant neoplasms through copy number variation detection. This study illustrates the potential clinical utility of a single metagenomic test to uncover the cause of undiagnosed acute illnesses due to cancer or infection using the same specimen.

Fine needle aspiration of salivary gland carcinomas with high-grade transformation: A multi-institutional study of 22 cases and review of the literature.

BACKGROUND: High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT. METHODS: The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed. RESULTS: The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively. CONCLUSIONS: SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma.

Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma.

BACKGROUND: PERP (p53 apoptosis effector related to PMP22) localizes to desmosomes and suppresses squamous cell carcinoma development. Loss of PERP leads to worse local control in head and neck squamous cell carcinoma (HNSCC), likely by destabilizing desmosomes. We evaluated PERP loss at HNSCC surgical margins as a predictor of local relapse. METHODS: Combining discovery (n = 17) and validation (n = 31) cohorts, we examined membranous PERP protein expression by immunohistochemistry in surgical mucosal margins with competing risk analysis of the relationship between local relapse and PERP expression. RESULTS: Of the 44 analyzable patients, the 2-year cumulative incidence of local relapse was 44.4% for the PERP-negative group and 16.4% for the PERP-positive group (P = .01). A trend toward worse progression-free survival (P = .09) and overall survival (P = .06) was observed with loss of PERP. CONCLUSIONS: PERP loss at surgical margins is associated with higher risk of local recurrence in HNSCC, warranting further evaluation in a larger prospective study.

Macrocystic (Mammary Analogue) Secretory Carcinoma: An Unusual Variant and a Pitfall in the Differential Diagnosis of Cystic Lesions in the Head and Neck.

Mammary analogue secretory carcinoma (MASC) is a relatively recently described salivary gland adenocarcinoma characterized by ETV6-NTRK3 gene fusion and in most cases indolent clinical behavior. The majority of tumors show an admixture of microcystic, solid, and tubular growth patterns but only a few cases with dominant macrocystic growth have been reported. We report 15 cases of macrocystic MASC. There were 11 men and 4 women (17 to 88 y age range, average 47 y). The patients presented with a painless cystic mass, the majority in the region of the parotid gland (n=13), as well as in submandibular gland (n=1) and the neck (n=1). All tumors were circumscribed measuring 1.0 to 4.0 cm in greatest diameter (mean: 1.75 cm). Twelve tumors were unilocular, while 3 were multilocular. The cystic spaces were predominantly lined by a single epithelial cell layer with focal areas in which the epithelium was multilayered with papillary and hobnail features. In 3 of the cases there were more solid foci of intracystic tumor characterized by papillary and/or microcystic growth. The neoplastic cells were round to oval with hyperchromatic to vesicular nuclei with centrally located nucleoli and eosinophilic or vacuolated cytoplasm. Tumor cells showed strong positivity for S100 protein and mammaglobin, while DOG1 was uniformly negative. A minority of cases showed focal p63 reactivity predominantly limited to the periphery of the cystic lining. ETV6 gene rearrangement was identified in 9 cases. Macrocystic MASC can simulate benign and malignant salivary gland lesions and needs to be included in the differential diagnosis of cystic lesions in the head and neck. To the best of our knowledge, our report represents the first series of macrocystic MASCs wholly focusing on this unusual variant.

A Young Woman With a Rapidly Growing Thoracic Tumor.

CASE PRESENTATION: A 38-year-old woman presented with 2 months of dry cough, progressive shortness of breath, central chest pain, nausea, vomiting, and dizziness. She was previously healthy and was not taking any medications. She denied fever, night sweats, or weight loss. She had a two pack-year smoking history and had quit smoking at 27 years of age. She denied drug use and had no recent travel history. Family history was pertinent for ovarian cancer, breast cancer, and colon cancer.

Virus-associated carcinomas of the head & neck: Update from the 2017 WHO classification.

Virus-associated carcinomas of the head and neck represent an unusual confluence of infections spread by viral transmission and cellular dysregulation resulting in carcinogenesis. While much remains to be elucidated about the exact progression from infection to cancer, a basic framework of viral biology can complement the pathologist's understanding of morphology. This context informs the pathologist's everyday practice, including selecting ancillary studies, communicating prognostically relevant findings, and participating in treatment planning. By comparing and contrasting the salient features of human papillomavirus-associated oropharyngeal carcinoma and Epstein-Barr virus-associated nasopharyngeal carcinoma, this review summarizes recent evidence to guide current practice.

Oncologic management of sinonasal undifferentiated carcinoma.

PURPOSE OF REVIEW: This article reviews the latest treatment paradigms in sinonasal undifferentiated carcinoma (SNUC). RECENT FINDINGS: The aggressive biology and associated advanced presentation of SNUC make successful treatment a challenge shared across medical specialties. Still, studies reporting outcomes in SNUC indicate that an aggressive treatment strategy consisting of surgery, radiation and chemotherapy offers the best chance of prolonged survival. SUMMARY: Successful treatment of SNUC requires highly specialized care at tertiary cancer treatment facilities. A better understanding of the biology of the disease coupled with increasing outcome reporting will lead to optimized treatment regimens.

Performance of the Afirma Gene Expression Classifier in Hürthle Cell Thyroid Nodules Differs from Other Indeterminate Thyroid Nodules.

BACKGROUND: The recently introduced Afirma gene expression classifier (AGEC) provides binary results (benign or suspicious) to guide management of cytologically indeterminate thyroid nodules. The AGEC is intended to reduce unnecessary surgeries for benign nodules, and management algorithms favor surgery for suspicious results. Limited data are available on the performance of this test for Hürthle cell nodules (HCNs). This study hypothesized that a predominance of Hürthle cells leads to an increased rate of suspicious AGEC results with a potential for overtreatment, despite a relatively low risk of malignancy. METHODS: The pathology databases from three tertiary care facilities were queried from 2010 to 2014 for fine-needle aspirates (FNAs) diagnosed as suspicious for Hürthle cell neoplasm (SHCN) or atypia of undetermined significance/follicular lesion of undetermined significance concerning for Hürthle cell neoplasm (AFHCN). Cytology diagnoses were rendered internally prior to AGEC testing. The patient demographics, FNA diagnosis, AGEC result, surgical procedure, and pathologic outcomes were recorded. RESULTS: The cohort consisted of 134 patients with HCNs. Prior to AGEC availability, 62 patients underwent surgery: 81% (50/62) of patients had surgery, and 34% (17/50) of the resected index nodules were malignant. After introduction of the AGEC, 72 patients underwent AGEC testing: 65% (47/72) of patients had surgery, and 13% (6/46) of the resected nodules were malignant. Thirty-two percent (23/72) of patients had a benign AGEC result and did not undergo surgery, and 4% (3/72) had surgery despite a benign AGEC result with benign final pathology, whereas 63% (45/72) of patients had suspicious AGEC results, with 96% of these patients (43/45) undergoing surgery, and 14% (6/43) of these index nodules were malignant. CONCLUSIONS: While 32% of tested patients declined surgery based on a benign AGEC, 86% of patients with suspicious AGEC findings had unnecessary surgery, reflecting a substantially lower rate of malignancy from what was previously reported for all indeterminate nodules. Given the approximate pretest malignancy risk of 25-35% for an FNA diagnosis of SHCN or AFHCN, a suspicious AGEC diagnosis does not increase the probability of malignancy in an HCN, and patients should be counseled accordingly.

The Fidelity of p16 Staining as a Surrogate Marker of Human Papillomavirus Status in Fine-Needle Aspirates and Core Biopsies of Neck Node Metastases: Implications for HPV Testing Protocols.

OBJECTIVES: The importance of detecting human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has resulted in a growing expectation for HPV testing of clinical samples. Although testing protocols vary, most pertain to primary tumor biopsies/resections. Testing of fine-needle aspirates and core biopsies (FNACBs) is advantageous, but it is unclear whether technical and biological factors adversely affect the fidelity of HPV detection in these samples. METHODS: Data was collected for 85 patients with regionally metastatic HNSCC that had undergone FNACB with HPV analysis as part of clinical care. HPV testing consisted of p16 immunostaining and HPV in situ hybridization (ISH). The FNACBs were compared with the subsequent biopsies/resections for HPV status. RESULTS: p16 staining was present in 60 cases (71%). p16 positivity was predictive of oropharyngeal origin (p<0.001) and correlated with the presence of HPV by ISH (98% correlation). On comparison of the metastases and primary cancers, the HPV status was concordant in 58 of 59 cases (98%). CONCLUSIONS: For patients with metastatic HNSCC, p16 staining reliably reflects the HPV status of the primary tumor. p16 staining of FNACBs may obviate the need for more invasive sampling of the primary cancer solely for the purpose of HPV testing.

Single-Laboratory Ruggedness Testing and Validation of a Modified QuEChERS Approach To Quantify 185 Pesticide Residues in Salmon by Liquid Chromatography- and Gas Chromatography-Tandem Mass Spectrometry.

In this study, we successfully applied a previously modified version of the QuEChERS approach to quantify pesticide residues in samples of fresh salmon. Analysis was performed using a combination of liquid and gas chromatography-tandem mass spectrometry (LC-MS/MS and GC-MS/MS). The validated QuEChERS method used ethyl acetate for the extraction solvent and involved two freezing steps and a C18 dispersive solid phase extraction for removal of lipids. Of the 228 pesticides initially screened, only 185 passed the method validation criteria (103 on LC-MS/MS and 82 on GC-MS/MS). In a quantitative validation, acceptable performances were achieved with overall recoveries of 70-120% and <20% RSD for 179 analytes (n = 7) over the course of five different extractions at 2 times the limit of quantification. Over 12 months, this method was used in the analysis of 708 salmon samples collected as part of the U.S. Department of Agriculture's Pesticide Data Program. Ruggedness testing conducted throughout the entire study showed this method to be robust and suitable for long-term use.

Interpersonal multisensory stimulation reduces the overwhelming distracting power of self-gaze: psychophysical evidence for 'engazement'.

One's own face and gaze are never seen directly but only in a mirror. Yet, these stimuli capture attention more powerfully than others' face and gaze, suggesting the self is special for brain and behavior. Synchronous touches felt on one's own and seen on the face of others induce the sensation of including others in one's own face (enfacement). We demonstrate that enfacement may also reduce the overwhelming distracting power of self-gaze. This effect, hereafter called 'engazement', depends on the perceived physical attractiveness and inner beauty of the pair partner. Thus, we highlight for the first time the close link between enfacement and engazement by showing that changes of the self-face representation induced by facial visuo-tactile stimulation extend to gaze following, a separate process likely underpinned by different neural substrates. Moreover, although gaze following is a largely automatic, engazement is penetrable to the influence of social variables, such as positive interpersonal perception.