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Simple Summary: Invasive lobular carcinoma represents a distinct histological type of breast cancer, characterised by morphological, genetic, and behavioural differences from other types. However, the behaviour of invasive lobular carcinomas is not uniform, and some tumours show poor outcome. This may attribute to the presence of aggressive variants. Therefore, we performed detailed investigation of a large series of cases to characterise this aggressive subtype of invasive lobular carcinoma. This subtype, which includes the pleomorphic and high-grade solid variants accounts for 14% of lobular carcinomas. It showed associations with unfavourable prognostic features, poor patient outcomes, and poor response to therapy when compared to classic lobular carcinoma and invasive ductal carcinoma of no special type. Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes. Methods: A large (n = 7140) well-characterised and histologically reviewed BC cohort with treatment and long-term follow-up data was investigated. The cohort was classified based on the WHO classification of tumours into main histological subtypes, including ILC and IDC-NST. ILCs were further classified into variants. Clinicopathological parameters and patient outcomes in terms of BC-specific survival (BCSS) and disease-free survival (DFS) were evaluated. Results: ILC constituted 11% of the cohort. The most common non-classic ILC variants were pleomorphic (pILC) and solid (sILC), constituting 19% of ILC. Compared to classic and related variants (alveolar, trabecular, papillary, and tubulolobular; cILC), pILC and sILC variants were associated with aggressive tumour characteristics. The histologic grade of ILC was an important prognostic variable. The survival patterns identified an aggressive ILC subtype encompassing pILC and high-grade sILC. These tumours, which comprised 14% of the cases, were associated with clinicopathological characteristics of poor prognosis and had high BC-specific death and recurrence rates compared not only to cILC (p < 0.001) but also to IDC-NST (p = 0.02) patients. Contrasting this, cILC patients had significantly longer BCSS and DFS than IDC-NST patients in the first 10 to 15 years of follow-up. Adjuvant chemotherapy did not improve the outcome of patients with aggressive ILC subtypes. Conclusions: pILC and high-grade sILC variants comprise an aggressive ILC subtype associated with poor prognostic characteristics and a poor response to chemotherapy. These results warrant confirmation in randomised clinical trials. [ABSTRACT FROM AUTHOR]

Aims: The method of diagnosis of ductal carcinoma in situ (DCIS) has changed since the 1980s. The aim of this audit was to assess changes in the preoperative diagnosis of DCIS since the introduction of needle core biopsy, particularly the proportion with a preoperative biopsy diagnosis of DCIS. Methods and results: The preoperative diagnoses of patients with a final diagnosis of DCIS in the surgical specimen were reviewed (i) in 809 patients who presented through breast screening from 1997 to 2021, and (ii) in all patients in 5 individual years at 5‐year intervals from 2000 to 2020 (254 in total). For screening‐detected DCIS the proportion with a preoperative diagnosis of DCIS increased from 75% to 98% over the study period. In a detailed analysis of all cases of DCIS in 5 separate years the proportion with a preoperative diagnosis of DCIS increased from 68% in 2000 to 96% in 2020. For high‐grade DCIS the proportion increased from 87% to 97%, and for low‐ or intermediate‐grade DCIS from 48% to 93%. The proportion of women who had vacuum‐assisted biopsy increased from 7% in 2000 to 58% in 2015. There was a small increase in the number of biopsies that had basal cytokeratin and oestrogen receptor immunohistochemistry to aid diagnosis. Conclusion: There has been an increase in the preoperative diagnosis of DCIS, particularly of low‐ or intermediate‐grade, over the last two decades. The increasing use of vacuum‐assisted biopsy is likely to be a major contributory factor to this increase. [ABSTRACT FROM AUTHOR]

Aims: Breast pathology is a challenging field, and discrepancies in diagnoses exist and can affect patient management. This study aims to review a breast referral practice and assess the pattern and frequency of breast lesions sent for an external expert review and evaluate potential impacts on patients' care. Methods and results: Seven hundred and forty cases that were referred to Nottingham City Hospital for a second opinion between 2019 and 2022 which have slides and reports were retrieved and reviewed. Reasons for referral, initial diagnosis, proffered specialist opinion and any discrepancy or potential impacts of management were assessed. The most frequent entities were papillary lesions (19%), fibroepithelial lesions (17%), invasive carcinomas that were sent for confirmation of the invasive diagnosis or subtyping of the invasive tumour (17%), intraductal epithelial proliferation with atypia (9%) and spindle cell lesions (8%). Other entities included biphasic tumours such as adenomyoepithelioma, as well as vascular and nipple lesions. Few cases were sent for prognostic classification or comments on the management, and in occasional cases no initial diagnosis was offered. After reviewing the cases by the expert pathologists, the initial diagnosis was confirmed or one of the suggested diagnoses was preferred in 79% of cases, including 129 cases (17%) in which the opinion resulted minor changes in the management. Significant changes in the classification of lesions were made in 132 cases (18%) which resulted in significant change in the patient management recommendation. In 14 cases (2%) a final classification was not possible, and further specialist opinion was obtained. Comments on the differential diagnosis and advice on further patient management were provided in most cases. Conclusions: This study demonstrates the value of external referral of challenging, rare and difficult to classify breast lesions. It also highlights the most common breast lesions that are likely to be challenging, and specialist opinion can refine their classification to improve patient care. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of different types of form-focused instruction (FFI) on the acquisition of French grammatical gender attribution. A quasi-experimental study was conducted with 140 participants in six intact French as a second language (L2) classes. The classes received six 80-minute instructional sessions consisting of FFI on only sublexical cues, FFI on both sublexical cues and pronunciation, or the control condition (two classes per condition). To measure the effects of the instructional conditions, a pretest, an immediate posttest, and a delayed posttest were administered. Results showed that the participants receiving FFI on only sublexical cues showed significant improvement in binary-choice, text-completion, and listening tasks, but not in an oral picture-description task. In contrast, those receiving FFI on both sublexical cues and pronunciation showed significantly higher scores on all tasks after the instructional sessions. The present study highlights the importance of pronunciation instruction in L2 grammar acquisition and its interdependence with lexical and morphological domains. [ABSTRACT FROM AUTHOR]

In order to investigate the characteristics and effects of peer feedback targeting second language (L2) pronunciation, the present study recruited 32 Mandarin-speaking learners of English who received five pronunciation instructional sessions through an instant messaging application on their smart phones. The phonological targets, types, and formats of peer feedback as well as its effects on their pronunciation (i.e., comprehensibility and accentedness) were examined. Results revealed that the participants mainly targeted segmental errors rather than suprasegmental errors and that they tended to provide more feedback on vowels rather than on consonants. Their feedback, delivered mainly in writing, was found to be effective in improving learners' comprehensibility, but not their accentedness. The findings demonstrate the potential of peer feedback complementary to teacher feedback in instructed L2 pronunciation and highlight the importance of training in optimizing the effectiveness of peer feedback. [ABSTRACT FROM AUTHOR]

Background and aims: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry‐equivocal score. Methods and results: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in‐situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2‐amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5–< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2‐non‐amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2‐amplified and HER2‐non‐amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2‐amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37–102.00; P = 0.02], and histological grade 3 in HER2 non‐amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61–19.00; P = 0.007). Conclusion: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry‐equivocal score who would benefit from NAT. [ABSTRACT FROM AUTHOR]

The present study investigated whether age of acquisition (AOA) is a significant predictor of the extent to which Korean learners of English perceive and produce two nonnative vowels and the extent to which their speech perception and production accuracy are linked. A total of 100 Korean learners of English with a varying range of AOA participated in the study by completing perception and production measurement tasks. Overall, there were significant AOA effects found in the case of Korean participants who moved to Canada before the age breakpoint range of 17.0 to 25.5, after which AOA failed to be a significant predictor of their perception and production accuracy. In addition, compared to late second language (L2) learners, early L2 learners more consistently demonstrated instances of significant perception-production correlation. This study concludes by highlighting the role of AOA in L2 speech acquisition, supporting the existence of a critical period for intelligible L2 pronunciation. [ABSTRACT FROM AUTHOR]

Fibroepithelial tumours of the breast are biphasic neoplasms composed of both epithelial and stromal elements, including the common fibroadenoma and the infrequent phyllodes tumour. The admixture of epithelium and stroma in the fibroadenoma shows intra- and pericanalicular patterns, and may display a variety of histological changes. Fibroadenoma variants include the cellular, juvenile, myxoid and complex forms. The cellular fibroadenoma may be difficult to distinguish from the benign phyllodes tumour. Stromal mitotic activity can be increased in fibroadenomas in the young and pregnant patients. Phyllodes tumours, neoplasms with the potential for recurrence, show an exaggerated intracanalicular growth pattern with broad stromal fronded architecture and stromal hypercellularity. They are graded into benign, borderline and malignant forms based on histological assessment of stromal features of hypercellularity, atypia, mitotic activity, overgrowth and the nature of the tumour borders. Classification of phyllodes tumours is imperfect, compounded by tumour heterogeneity with overlapping microscopic features among the different grades, especially in the borderline category. Malignant phyllodes tumours can metastasise and cause death. Determining which phyllodes tumours may behave aggressively has been difficult. The discovery of MED12 mutations in the pathogenesis of fibroepithelial tumours, together with other gene abnormalities in the progression pathway, has allowed refinements in diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Objectives: Traditionally B3 breast lesions are treated surgically, but overtreatment is a concern, as the majority have a final benign diagnosis. A national screening program introduced vacuum-assisted excision (VAE) for managing B3 lesions in late 2016. This retrospective study aimed to assess the outcomes associated with this approach. Methods: All B3 lesions diagnosed between 01/2017 and 12/2019 were identified at two centres. Information was obtained on the initial biopsy and final histology, and method of VAE image guidance, needle size and number of cores. Lesions were excluded if there was cancer elsewhere in the breast at the time of diagnosis; the lesion was not suitable for VAE due to position in the breast or had B3 pathology for which open biopsy was still required. The final decision to offer VAE was always made at a multidisciplinary meeting (MDM). Risk difference was used to test the significance at p ≤.05. Results: In total, 258 B3 lesions were diagnosed, 105 (40.7%) met the inclusion criteria and underwent VAE. VAE was performed under X-ray (89/105) or ultrasound guidance (16/105), taking an average of 18.5 cores with the 10-G needle or 10.8 cores with the 7-G needle. Nine cases (8.6%) were upgraded to a malignant diagnosis following VAE. Malignancy was found in 15.5% (9/58) of B3 lesions with epithelial atypia, but in none without atypia (0/47) (p =.004). No new lesions or malignancy has occurred at the site of the VAE with an average mammographic follow-up of 2.2 years. Conclusion: Upgrade to malignancy following VAE was uncommon (8.6%) and associated with atypia in the initial biopsy. VAE is an alternative approach to the management of B3 lesions, reducing open surgical procedures. Key Points: • Upgrade to malignancy after a vacuum-assisted excision of a B3 breast lesion is uncommon with an 8.6% upgrade rate. • The risk of a malignant diagnosis after a vacuum-assisted excision was significantly higher for B3 lesions with atypia compared to those without (+15.5% difference, p =.004). [ABSTRACT FROM AUTHOR]

Background: The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).Methods: 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.Results: 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).Conclusion: No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy. [ABSTRACT FROM AUTHOR]

Aims: Phyllodes tumours (PTs) represent an unusual but complex group of breast lesions with a tendency to recur locally and, less commonly, metastasise. On core biopsies, their appearances can be difficult to discriminate from those of other fibroepithelial lesions, which may compromise their surgical management. The aims of this study were to assess the preoperative diagnosis of PTs and to evaluate the impacts of surgical management and morphological features on their behaviour. Methods and results: We combined datasets from three centres over two decades, including core biopsies, excision specimens, and follow‐up. Core biopsy results were compared with final excision specimens. The relationships of surgical procedure and morphological features with local recurrence (LR) and metastasis were assessed. Two hundred and forty‐one PTs were studied. Core biopsy resulted in a diagnosis of possible or definite PT in 76% of cases. Malignant tumours were more likely to be larger, occurred at an older age, and were surgically more challenging, with difficulties being encountered in achieving negative margins. There were 12 cases (5%) that showed LR alone, and another six cases (2.5%) that had distant metastases. Morphological features associated with adverse outcome were grade of PT, increased mitotic counts, necrosis, infiltrative margins, stromal atypia, and heterologous components. Both LR and metastatic behaviour correlated with larger size and distance to margins. Conclusions: Our results suggest that excision margins have a significant impact on LR of PT, whereas metastatic behaviour is influenced by tumour biology. We add to the evidence base on histological features of tumours that contribute to long‐term outcomes of PT patients. [ABSTRACT FROM AUTHOR]

A 63-year-old woman presented with a clinically malignant mass. Core biopsy showed features resembling endometriosis. The glands were GATA3 and oestrogen receptor positive consistent with mammary origin and had no myoepithelial layer. The excision also showed a fibroepithelial component with stromal overgrowth, frequent mitoses and invasive margin consistent with a malignant phyllodes tumour. KMT2D and SETD2 mutations were present in both the conventional phyllodes tumour and endometriosis-like areas and are also described in endometriosis raising interesting questions about these lesions. This unusual pattern is a potential diagnostic pitfall, so it is helpful to be aware of it. [ABSTRACT FROM AUTHOR]

Background: Birds show adaptations in limb bone shape that are associated with resisting locomotor loads. Whether comparable adaptations occur in the microstructure of avian cortical bone is less clear. One proposed microstructural adaptation is laminar bone in which the proportion of circumferentially-oriented vascular canals (i.e., laminarity) is large. Previous work on adult birds shows elevated laminarity in specific limb elements of some taxa, presumably to resist torsion-induced shear strain during locomotion. However, more recent analyses using improved measurements in adult birds and bats reveal lower laminarity than expected in bones associated with torsional loading. Even so, there may still be support for the resistance hypothesis if laminarity increases with growth and locomotor maturation. Methods: Here, we tested that hypothesis using a growth series of 17 homing pigeons (15-563 g). Torsional rigidity and laminarity of limb bones were measured from histological sections sampled from midshaft. Ontogenetic trends in laminarity were assessed using principal component analysis to reduce dimensionality followed by beta regression with a logit link function. Results: We found that torsional rigidity of limb bones increases disproportionately with growth, consistent with rapid structural compensation associated with locomotor maturation. However, laminarity decreases with maturity, weakening the hypothesis that high laminarity is a flight adaptation at least in the pigeon. Instead, the histological results suggest that low laminarity, specifically the relative proportion of longitudinal canals aligned with peak principal strains, may better reflect the loading history of a bone. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to review the histological features useful for the identification of metastases to the breast and to investigate the impression that this diagnosis has become more common. Methods and results: The histological features of metastases to the breast from 2008 to 2018 were reviewed. Seventy‐four biopsies from 66 patients were identified: 1% compared with primary carcinoma of the breast. Non‐haematological metastases comprised 0.75% compared with 0.3% in a series from 1996 to 2005. The most common tumour types were pulmonary carcinoma (22), lymphoma (15), melanoma (13), gastrointestinal carcinoma (eight) and serous papillary carcinoma (four). In 73% there were histological features that were not typical of primary mammary carcinoma. Some metastases were histologically similar to breast cancer and the history was essential to making the correct diagnosis. Useful histological clues included small‐cell morphology for pulmonary carcinoma, glands containing necrosis for gastrointestinal carcinoma, intranuclear inclusions, marked pleomorphism and spindle cells for melanoma, clear cells for renal carcinoma, papillary architecture for serous papillary carcinoma and sheets of centroblasts or nodules of centroblasts and centrocytes for lymphoma. Useful immunohistochemical markers included TTF‐1 for pulmonary carcinoma, S100, melan‐A and HMB45 for melanoma, CK20 and CDX2 for colorectal carcinoma, PAX8 and WT1 for serous papillary carcinoma and lymphoid markers for lymphomas, in addition to the absence of expression of mammary markers ER, GATA3 and GCDFP‐15. Conclusion: The majority of metastases to the breast have histological clues to the diagnosis. Immunohistochemistry is helpful. This diagnosis is being made more frequently. [ABSTRACT FROM AUTHOR]

Objectives: Postoperative hemorrhage is a serious complication of tonsillectomy, with secondary bleeding rates affecting up to 0.8% to 3% of patients. Although these bleeds are anecdotally perceived as occurring more frequently at night, the occurrence of hemorrhage relative to the time of day has not been investigated. We measured the frequency of post-tonsillectomy hemorrhage onset relative to the time of day.Methods: We reviewed electronic medical records of all patients who experienced postprocedural hemorrhage (International Classification of Disease, Ninth Edition [ICD-9] 998.11, ICD-10 J95.830 at two hospitals within a tertiary academic health system in a 10-year period). Patient demographics, time of bleed onset, emergency room [ED] arrival time, and management (operating room vs. observation) were abstracted. Patients without a recorded bleeding time were excluded. Time of bleed onset was categorized as morning (6:01 am-12 pm), afternoon (12:01 pm-6 pm), evening (6:01 pm-12 am), or overnight (12:01 am-6 am). Chi-square goodness of fit test was used to assess the distribution of hemorrhage timing (P ≤ 0.05).Results: A total of 7,396 patients underwent tonsillectomy May 2008 through May 2018, among whom 121 (2%) post-tonsillectomy hemorrhage patients were identified. Among the 104 patients with ED arrival times, 29 (28%) arrived in the morning; 15 (14%) arrived in the afternoon; 40 (38%) arrived in the evening; and 20 (19%) arrived overnight (P = 0.003). Sixty patients (mean age 17.1 years, standard deviation 16.6) had a recorded timing of bleed onset. Bleed onset occurred most commonly overnight (24, 40%), followed by evening (21, 35%), afternoon (11, 18%), and morning (4, 7%) (P = 0.0007).Conclusion: In this cohort, post-tonsillectomy hemorrhage occurred most frequently between midnight and 6 am. Our findings confirm anecdotal experience and provide data in setting caregiver expectations.Level Of Evidence: 4 Laryngoscope, 130:1823-1827, 2020. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Scheduling otolaryngology interviews may be a challenge for residency applicants due to overlapping interview dates. Our objective was to identify otolaryngology interview date patterns and scheduling conflicts over the past six application cycles.Study Design: Retrospective review of otolaryngology online forums (Otomatch.com and Student Doctor Network).Methods: Online threads related to residency interview dates posted during the 2012 to 2013 through 2017 to 2018 interview seasons on Otomatch.com were reviewed. Program directors were contacted to complete any missing data. The χ- goodness-of-fit test and the χ2 test of independence was used to compare proportions. Analysis of variance was used to compare values across years.Results: Data from an average of 98 programs (99%) per year were obtained. The majority of invitations arrived late October (49%), followed by early November (37.1%). Interviews occurred primarily in December (48.4%) and January (37.5%). Programs on average scheduled 2.47 (range, 0-4) interview dates. Most interviews fell on Fridays (28.7%) and Saturdays (22.7%) (P < .0001), with an increasing trend toward interviewing on consecutive days. There was substantial overlap in interview dates, with six dates alone accounting for an average of 31.3% of all interviews in a given interview cycle.Conclusions: The majority of otolaryngology interviews occur in December or January and fall on a Friday or Saturday. There is considerable overlap with the potential for scheduling conflicts. Our findings can help set expectations for applicants regarding interview invitations, as well as a strategy for scheduling interviews.Level Of Evidence: NA Laryngoscope, 129:2280-2285, 2019. [ABSTRACT FROM AUTHOR]

The orientation of vascular canals in primary bone may reflect differences in growth rate and/or adaptation to biomechanical loads. Previous studies link specific canal orientations to bone growth rates, but results between different taxa are contradictory. Circumferential vascular canals (forming laminar bone) have been hypothesized to reflect either (or both) rapid growth rate or locomotion-induced torsional loading. Previous work on the hindlimb biomechanics in the emu shows that the femur and tibiotarsus experience large shear strains, likely resulting from torsional loads that increase through ontogeny. Here, we test how growth rate and biomechanical loading affect bone laminarity in wing and hindlimb elements from growing emu (2-60 wks). If laminar bone is an adaptation to torsion-induced shear strains, it should increase from juveniles to adults. Alternatively, if bone laminarity reflects rapid growth, as has been shown previously in emu, it should be abundant in fast-growing juveniles and decrease with age. Transverse mid-shaft histological sections from the limb bones (femur, tibiotarsus, humerus, ulna, and radius) were prepared and imaged. Growth rates were measured using fluorescent bone labels. Vascular canal orientation was quantified using laminarity index (proportion of circumferential canals). Principal components analysis was performed to convert highly correlated variables (i.e., mass, age, growth rate, and shear strain) into principal components. Random-intercept beta regression modeling determined which principal components best explained laminarity. The fastest growth rates were found in young individuals for all five skeletal elements. Maximum growth rate did not coincide with peak laminarity. Instead, in the femur and tibiotarsus, elevated laminarity is strongly correlated with adult features such as large size, old age, and modest growth rate. This result is contrary to predictions made based on a previous study of emu but is consistent with results observed in some other avian species (penguin, chicken). Shear strain in the caudal octant of the femur and tibiotarsus is positively correlated with laminarity but has a weaker effect on laminarity relative to mass, age, and growth rate. Laminarity in the wing elements is variable and does not correlate with ontogenetic factors (including mass, age, and growth rate). Its presence may relate to relaxed developmental canalization or a retained ancestral feature. In conclusion, ontogeny (including growth rate) is the dominant influence on vascular canal orientation at least in the hindlimb of the emu. [ABSTRACT FROM AUTHOR]

Objectives: Collaboration and diversity of expertise are increasingly emphasized in the production of successful research. However, the degree of cross-disciplinary collaboration in otolaryngology research is unknown. In this study, we quantify cross-disciplinary collaboration in otolaryngology publications.Methods: We retrospectively analyzed authorship and study characteristics for all original articles published from January 2014 to December 2016 in three key peer-reviewed otolaryngology journals: Laryngoscope, Otolaryngology-Head & Neck Surgery, and JAMA Otolaryngology-Head & Neck Surgery. Author affiliations and online searches were used to determine author's primary discipline. Subspecialty topic of article, study design, and funding sources were also recorded. Fisher exact test was used to compare characteristics of articles with and without cross-disciplinary authorship.Results: A total of 2,378 articles were reviewed, of which 1,312 (55%) articles had one or more cross-disciplinary collaborators. Among articles with cross-disciplinary collaboration, the greatest representation of disciplines was from other medical specialties (1,109, 50.9%), epidemiology/biostatistics (266, 12.2%), pathology/histology (175, 8.0%), biologic sciences (168, 7.7%), and radiology/imaging (144, 6.6%). Cross-disciplinary studies had a significantly greater proportion of articles on the topic of head and neck compared to studies without collaboration (P < 0.0001). The proportion of funded studies was significantly greater among articles with collaboration compared to articles without collaboration (P < 0.0001).Conclusion: The majority of articles published during a 3-year period in three influential otolaryngology journals had cross-disciplinary collaboration. There is potential opportunity for further leveraging expertise, funding opportunities, and dissemination of key findings through collaborative research.Level Of Evidence: NA Laryngoscope, 129:1800-1805, 2019. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported up to 50% of ductal carcinoma in situ (DCIS), is HER2 positive, but the frequency of HER2-positive invasive breast cancer (IBC) is lower. The aim of this study is to characterise HER2 status in DCIS and assess its prognostic value.Methods: HER2 status was evaluated in a large series of DCIS (n = 868), including pure DCIS and DCIS associated with IBC, prepared as tissue microarrays (TMAs). HER2 status was assessed using immunohistochemistry (IHC) and chromogenic in situ hybridisation (CISH).Results: In pure DCIS, HER2 protein was over-expressed in 9% of DCIS (3+), whereas 15% were HER2 equivocal (2+). Using CISH, the final HER2 status was positive in 20%. In mixed DCIS, HER2 amplification of the DCIS component was detected in 15% with amplification in the invasive component of only 12%. HER2-positive DCIS was associated with features of aggressiveness (p < 0.0001) and more frequent local recurrence (p = 0.03). On multivariate analysis, combined HER2+/Ki67+ profile was an independent predictor of local recurrence (p = 0.006).Conclusions: The frequency of HER2 positivity in DCIS is comparable to IBC- and HER2-positive DCIS is associated with features of poor prognosis. The majority of HER2 over-expression in DCIS is driven by gene amplification. [ABSTRACT FROM AUTHOR]

Objectives: Otolaryngology applicants routinely decry conflicting interview dates because this limits the number of interviews that one can attend, despite being offered an interview. Conversely, applicants also perceive that a large number of interviews are offered to a minority of applicants. We sought to verify and quantify the inequality in distribution of interviews attended.Study Design: Retrospective analysis of the National Resident Matching Program (NRMP) 2016 Charting Outcomes in the Match and Electronic Residency Application Service (ERAS) historic specialty data.Methods: The Gini coefficient, a commonly used indicator of economic inequality, was calculated using data from the 2016 Charting Outcomes in the Match to estimate the distribution of interviews attended. This data was compared to nine other specialties, comprising a wide range of competitiveness and specialty size.Results: 26% (110 of 416) of otolaryngology applicants accounted for half (1,721 of 3,426) of all possible interview positions. The Gini coefficient ranged from 0.43 to 0.84 across 10 specialties, with a higher coefficient indicating higher inequality. The Gini coefficient among otolaryngology applicants was 0.43, indicating lower inequality than most other specialties. When including only applicants who interviewed, the Gini coefficient was 0.23.Conclusion: There is an unequal distribution of interview invitations, which likely reflects the reality of asymmetry in applicant competitiveness. Otolaryngology demonstrates the greatest equality in distribution, which may stem from a greater burden of hoarding. The specialty's perceived competitiveness mitigates factors such as cost and time, essentially encouraging more people to take as many interviews as they can.Level Of Evidence: NA Laryngoscope, 129:627-633, 2019. [ABSTRACT FROM AUTHOR]

Cocoa fermentation is an essential step for chocolate production whereby flavor potential is generated and bitterness and astringency are moderated. To facilitate fermentation research in laboratories geographically distant from cocoa-growing regions, and to simplify and control the fermentation system, a laboratory fermentation model system was developed. The model system consisted of dried unfermented beans, artificial pulp medium, and laboratory incubator to control temperature and aeration. The model system developed in this study showed a succession of key microorganisms including Saccharomyces cerevisiae, Lactobacillus plantarum, Lactobacillus fermentum, Acetobacter pasteurianus, and Acetobacter tropicalis. The pH of cocoa beans decreased to an acceptable final pH (4.8). Sugars were well consumed and acetic acid and ethanol were produced during fermentation. Desirable volatile compounds including phenylethyl alcohol, acetoin, 2-phenylethyl acetate, and 3-methylbutyl acetate increased in the cocoa beans during fermentation. In addition, the concentration of polyphenols decreased with fermentation. These results lead to the conclusion that the model system developed in this study was able to simulate the microbial and chemical changes occurring in in situ cocoa fermentation. This laboratory-scale model system will enable systematic examination of the effects of process parameters on fermented bean quality. [ABSTRACT FROM AUTHOR]

Patient race/ethnicity affects health care utilization, provider trust, and treatment choice. It is uncertain how these influences affect pediatric care. We performed a systematic review (PubMed, Scopus, Web of Science, PsycINFO, Cochrane, and Embase) for articles examining race/ethnicity and parental treatment decision-making, adhering to PRISMA methodology. A total of 9200 studies were identified, and 17 met inclusion criteria. Studies focused on treatment decisions concerning end-of-life care, human papillomavirus vaccination, urological surgery, medication regimens, and dental care. Findings were not uniform between studies; however, pooled results showed (1) racial/ethnic minorities tended to prefer more aggressive end-of-life care; (2) familial tradition of neonatal circumcision influenced the decision to circumcise; and (3) non-Hispanic Whites were less likely to pursue human papillomavirus vaccination but more likely to complete the vaccine series if initiated. The paucity of studies precluded overarching findings regarding the influence of race/ethnicity on parental treatment decisions. Further investigation may improve family-centered communication, parent engagement, and shared decision-making. [ABSTRACT FROM AUTHOR]

There are an estimated 700,000 to 1 million transgender individuals living in the United States alone.1,2 Although these individuals require the same, if not greater, level of surgical care due to the importance of gender-affirming surgery, they often require medical treatment involving cross-sex hormone therapy or medications, which block the effects of endogenous hormones. The rate of VTE was highest with oral estrogen supplementation, particularly ethinylestradiol, and lowest with transdermal estrogen.3 As with cisgender women, the risk of VTE in transgender women was highest in the first year after starting estrogen supplementation and among smokers. [Extracted from the article]

This study did have limitations in that a minimal number of skin incisions were made in patients undergoing rhinoplasty and the long-term effects of isotretinoin use could not be assessed as patients were given a short preoperative course. Oral isotretinoin, otherwise known as Accutane, is frequently prescribed for the management of acne vulgaris and has been shown to be an effective option for patients. [Extracted from the article]

Aims Metaplastic breast carcinoma ( MBC) is a rare type of breast cancer; its diagnosis in routine practice can be challenging, and may require immunohistochemical ( IHC) characterization if no conventional invasive or in-situ carcinoma is present. Previous IHC studies of MBC often had a small sample size and did not investigate the different histological subtypes. This study aimed to assess the immunoprofile of MBC subtypes in a large series. Methods and results A total of 172 MBC diagnosed in routine and referral practice in Nottingham during 26 years were reviewed by three breast pathologists. In addition, data on the immunoprofile of 730 MBC in 61 published studies were analysed. The antibodies to a broad spectrum of cytokeratins ( AE1/ AE3 and MNF116) are most frequently positive in MBC (approximately 80%). Basal cytokeratins (34βE12, CK5/6, CK14 and CK17) are positive in approximately 70%. Luminal cytokeratins ( CK8/18, CK7 and CK19) are positive in approximately 30-60%. Myoepithelial markers are also frequently positive, particularly p63. Oestrogen receptor ( ER), progestogen receptor ( PR) and HER2 are usually all negative. CD34 (a marker often positive in phyllodes tumours) is consistently negative in MBC. Conclusion This study provides data on the frequency of expression of a wide range of markers in MBC based on a large number of tumours. No consistent immunophenotype was identified and no individual marker was positive in all tumours, most probably reflecting the morphological and molecular heterogeneity of this tumour class and the practical need to use a panel of different antibodies when trying to establish the diagnosis of metaplastic breast carcinoma. [ABSTRACT FROM AUTHOR]

Aims Previous concordance studies examining accuracy of breast diagnosis by pathologists, typically targeting difficult, histologically challenging breast lesions using artificial and restrictive environments, have reported aberrantly high levels of diagnostic discordance. The results of these studies may be misinterpreted by non-pathologists and raise concerns relating to routine practice. This study aims to assess the diagnostic agreement among UK breast pathologists. Methods Two hundred and forty consecutive breast lesions, submitted by participants from their routine practice, included in the UK National Health Service Breast Screening Programme ( NHSBSP) breast pathology EQA scheme during the last 10 years were reviewed. An average of approximately 600 participants viewed each case. Data on diagnostic categories (benign, atypical, in-situ malignant and invasive malignant) were collected. In this study, benign and atypical diagnoses were grouped together. Results The overall diagnostic agreement level was in the almost perfect range. Thirty-five cases (14.6%) showed diagnostic concordance of ≤95%. Reasons for discordance included one or more of: (1) scheme methodology limitations such as: (i) miscoding of certain lesions (e.g. phyllodes tumours and lobular neoplasia) ( n = 7) and (ii) variable representation of the index lesion on glass slides ( n = 18); and (2) diagnostically challenging cases that may be interpreted more easily using immunohistochemistry ( n = 28). These latter included benign and malignant papillary lesions ( n = 12), complex sclerosing lesions ( n = 7), intraductal epithelial proliferative lesions ( n = 6) and an unusual special tumour type ( n = 1). Further review identified pathologists' misinterpretation in 13 cases (5.4%), with an average discordance rate of only 4.2%. Conclusions The performance of breast pathologists is high. Exclusion of the effect of the scheme methodology limitations highlights further the high performance rate and identifies true diagnostically challenging entities. These difficult cases may benefit from additional diagnostic work-up and second opinions. [ABSTRACT FROM AUTHOR]

This study investigated whether different types of corrective feedback (CF) in second language speech perception training have differential effects on second language speech production. One hundred Korean learners of English were assigned to five different groups and participated in eight computer-assisted perception training sessions focusing on English vowels. While no CF was provided to the control group, participants in the four treatment groups received one of three types of auditory CF or a visual type of CF. A pretest, an immediate posttest, and a delayed posttest each consisted of a production measurement at a controlled-speech level. Results revealed that the extent to which the participants’ production accuracy benefited from the perception training depended on CF type. In addition, by adopting the perception accuracy data by Lee and Lyster (2016b), the current study found that improvement in perception accuracy was a significant predictor of improvement in production accuracy. [ABSTRACT FROM PUBLISHER]

This study investigated the effects of different types of corrective feedback (CF) provided during second language (L2) speech perception training. One hundred Korean learners of L2 English, randomly assigned to five groups ( n = 20 per group), participated in eight computer-assisted perception training sessions targeting two minimal pairs of English vowels. Four treatment groups each received a different type of CF; three groups received one of three types of auditory CF and a fourth group received a visual type of CF; the control group did not receive CF. Results of pretests, immediate posttests, and delayed posttests showed that, in comparison to the control group, the groups that received auditory CF improved significantly in trained over untrained words, whereas the group that received visual CF fared less well. These results are discussed in terms of the benefits of auditory CF types, especially CF combining target and nontarget forms. [ABSTRACT FROM AUTHOR]

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens. [ABSTRACT FROM AUTHOR]

Aims The recent American Society of Clinical Oncology/College of American Pathologists guidelines for human epidermal growth factor receptor 2 ( HER2) testing in breast cancer recommend repeat testing based on tumour grade, tumour type, and hormone receptor status. The aim of this study was to test the value of these criteria. Methods and results HER2 status was concordant in the core biopsies and excision specimens in 392 of 400 invasive carcinomas. The major reasons for discordance were amplification around the cut-off for positivity and tumour heterogeneity. Of 116 grade 3 carcinomas that were HER2-negative in the core biopsy, four were HER2-positive in the excision specimen. Three of these four either showed borderline negative amplification in the core biopsy or were heterogeneous. None of the 55 grade 1 carcinomas were HER2-positive. Review of repeat testing of HER2 in routine practice suggested that it may also be of value for multifocal tumours and if recommended by the person assessing the in-situ hybridization. Conclusions Mandatory repeat HER2 testing of grade 3 HER2-negative carcinomas is not appropriate. This is particularly true if repeat testing is performed after borderline negative amplification in the core biopsy or in HER2-negative heterogeneous carcinomas. [ABSTRACT FROM AUTHOR]

Malaria control efforts have been continuously stymied by drug-resistant strains of Plasmodium falciparum, which typically originate in Southeast Asia prior to spreading into high-transmission settings in Africa. One earlier proposed explanation for Southeast Asia being a hotbed of resistance has been the hypermutability or “Accelerated Resistance to Multiple Drugs” (ARMD) phenotype, whereby multidrug-resistant Southeast Asian parasites were reported to exhibit 1,000-fold higher rates of resistance to unrelated antimalarial agents when compared to drug-sensitive parasites. However, three recent studies do not recapitulate this hypermutability phenotype. Intriguingly, genome sequencing of recently derived multidrug-resistant Cambodian isolates has identified a high proportion of DNA repair gene mutations in multidrug-resistant parasites, suggesting their potential role in shaping local parasite evolution. By adapting fluctuation assays for use in P. falciparum, we have examined the in vitro mutation rates of five recent Cambodian isolates and three reference laboratory strains. For these studies we also generated a knockout parasite line lacking the DNA repair factor Exonuclease I. In these assays, parasites were typed for their ability to acquire resistance to KAE609, currently in advanced clinical trials, yielding 13 novel mutations in the Na+/H+-ATPase PfATP4, the primary resistance determinant. We observed no evidence of hypermutability. Instead, we found evidence of a mild mutator (up to a 3.4-fold increase in mutation rate) phenotype in two artemisinin-resistant Cambodian isolates, which carry DNA repair gene mutations. We observed that one such mutation in the Mismatch Repair protein Mlh1 contributes to the mild mutator phenotype when modeled in yeast (scmlh1-P157S). Compared to basal rates of mutation, a mild mutator phenotype may provide a greater overall benefit for parasites in Southeast Asia in terms of generating drug resistance without incurring detrimental fitness costs. [ABSTRACT FROM AUTHOR]

To what extent do second language (L2) learners benefit from instruction that includes corrective feedback (CF) on L2 speech perception? This article addresses this question by reporting the results of a classroom-based experimental study conducted with 32 young adult Korean learners of English. An instruction-only group and an instruction + CF group were exposed to five 1-hr form-focused lessons that drew learners’ attention to the nonnative phonemic contrast /i/-/ɪ/, but only the instruction + CF group was given relevant feedback. Forced-choice identification tasks were completed by participants in a pretest, an immediate posttest, and a delayed posttest. The two groups showed similar accuracy on the pretest; however, the instruction + CF group outperformed the instruction-only group on the immediate and delayed posttests as well as on unfamiliar words. The significant predictors for these differences turned out to be perceptual accuracy vis-à-vis /ɪ/-natural and /ɪ/-synthesized sounds. These findings are discussed in terms of the pivotal role played by CF in developing accuracy in L2 speech perception. [ABSTRACT FROM AUTHOR]

Aim This survey investigated the variation in the use of the breast core biopsy categories B1 normal and B2 benign. Method A survey with case scenarios was circulated to 701 breast pathologists in the UK. Results The response rate was 40%. If there was concordance between the radiological and histological findings, then there was a clear consensus on the appropriate B category. However, if there was discordance between the radiological and histological findings, then frequently there was poor agreement on the appropriate category. Analysis of these cases and supplementary questions on the criteria used to make a pathological categorisation showed that some pathologists are influenced by the radiological features or by the multidisciplinary discussion, rather than just using the histological features. Conclusions This survey shows that pathologists frequently do not follow the National Health Service breast screening guideline that B categories should be based solely on the histological changes. [ABSTRACT FROM AUTHOR]

Aims Pleomorphic adenoma ( PA) of the breast is a rare tumour seen usually in postmenopausal women. Although PA of the salivary glands ( SG) is recognized to be a benign tumour, the nature and biology of similar tumours seen in the breast remains to be defined. The aim of this study was to describe PA of the breast that was reported on core biopsy as an invasive matrix-producing metaplastic breast carcinoma ( MBC). Methods and results A core biopsy from a clinically malignant retroareolar mass showed mildly atypical polygonal cells with surrounding myxoid stroma. Immunohistochemistry showed expression of basal and luminal cytokeratins, but oestrogen receptor, human epidermal growth factor receptor 2 ( HER2) and myoepithelial markers were negative. The excision specimen showed similar features, but in addition the stroma showed cartilage and bone. Also it was clear that the lesion was circumscribed and merged with a sclerosed papillary lesion consistent with what has been described as mammary PA. Conclusion This lesion shows an overlap of morphology and immunophenotype with SG- PA and with MBC. The majority of mammary PAs have a benign behaviour, but local recurrence and development of carcinoma occur. We propose a new terminology of pleomorphic adenoma-like tumour of the breast to reflect the uncertain nature of these tumours and help guide management decisions. [ABSTRACT FROM AUTHOR]

Graviportal taxa show an allometric increase of the cross-sectional area of supportive bones and are assumed to display microanatomical changes associated with an increase in bone mass. This evokes osteosclerosis (i.e. an increase in bone compactness observed in some aquatic amniotes). The present study investigates the changes in bones' microanatomical organization associated with graviportality and how comparable they are with aquatically acquired osteosclerosis aiming to better understand the adaptation of bone to the different associated functional requirements. Bones of graviportal taxa show microanatomical changes that are not solely attributable to allometry. They display a thicker cortex and a proportionally smaller medullary cavity, with a wider transition zone between these domains. This inner cancellous structure may enable to better enhance energy absorption and marrow support. Moreover, the cross-sectional geometric parameters indicate increased resistance to stresses engendered by bending and torsion, as well as compression. Adaptation to a graviportal posture should be taken into consideration when analyzing possibly amphibious taxa with a terrestrial-like morphology. This is particularly important for palaeoecological inferences about large extinct tetrapods that might have been amphibious and, more generally, for the study of early stages of adaptation to an aquatic life in amniotes. [ABSTRACT FROM AUTHOR]

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed. [ABSTRACT FROM AUTHOR]

Although most breast spindle cell lesions (BSCLs) are rare, they constitute a wide spectrum of diseases, ranging from reactive processes to aggressive malignant tumours. Despite their varied histogenesis and behaviour, some lesions show an overlap of morphological features, making accurate diagnosis a challenging task, particularly in needle core biopsies. Clinical history and immunohistochemistry can help in making a correct diagnosis in morphologically challenging cases. To make an accurate diagnosis, it is important to maintain a wide differential diagnosis and be familiar with the diverse morphological appearances of these different entities. BSCLs can generally be classified into bland-looking and malignantlooking categories. In the former, the commonest diagnosis is scarring. However, it is important to distinguish low-grade spindle cell metaplastic breast carcinoma from other benign entities, as the management is clearly different. In the malignant category, it is important to differentiate metaplastic carcinoma from other malignant primary and metastatic malignant spindle cell tumours of the breast, such as malignant phyllodes tumour, angiosarcoma, and melanoma. This review focuses on the classification and histological and molecular diagnosis of various BSCLs, with an emphasis on the diagnostic approach, including in core biopsies. [ABSTRACT FROM AUTHOR]

This case report describes the use of CO2 laser and quadrivalent human papillomavirus (HPV) vaccination in two patients with nasopharyngeal HPV11-positive recurrent respiratory papillomas (RRP). These patients initially underwent CO2 laser excision but developed recurrent lesions and underwent HPV vaccination as adjunct therapy. The recurrent lesions shrank after vaccination and were again excised with CO2 laser. Subsequently, these patients had no recurrence of lesions on long-term follow-up at 33 months or 6 years after surgery. Thus, in patients with nasopharyngeal RRP, resection with CO2 laser, and HPV vaccination as adjunct therapy should be considered in HPV11-associated cases. Laryngoscope, 127:2279-2281, 2017. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Congenital pyriform aperture stenosis (CPAS) is a form of nasal obstruction caused by congenital narrowing of the maxilla at the medial processes. Traditionally, surgical correction involves a sublabial approach with subperiosteal dissection, widening of the aperture by drilling, and the use of nasal stents postoperatively. Although this approach may lead to symptomatic improvement, it alone may fail to provide a patent airway secondary to unaddressed posterior narrowing. Additionally, the use of stents is problematic because they are prone to clogging and can cause internal nasal scarring and septal or alar necrosis. We present the surgical management of this condition in six patients using a novel approach that aims to correct these limitations by including both the traditional sublabial procedure and an endonasal reduction of the inferior turbinates, without the use of stents postoperatively. Study Design Retrospective chart review. Methods Review of the medical records of six consecutive patients aged 2 weeks to 7 months, who underwent repair of CPAS via a sublabial ostectomy and endonasal inferior turbinate reduction from 2009 to 2012. Results All six patients were clear of airway obstruction postoperatively and at follow-up. Conclusion This is an alternative approach that leads to symptomatic improvement for CPAS patients without the morbidity associated with stent use. Level of Evidence 4. Laryngoscope, 125:1460-1464, 2015 [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and falsenegative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results. [ABSTRACT FROM AUTHOR]

During locomotion over land, vertebrates’ limb bones are exposed to loads. Like most biological structures, limb bones have a capacity to withstand greater loads than they usually experience, termed a safety factor (SF). How diverse are limb-bone SFs, and what factors correlate with such variation? We have examined these questions from two perspectives. First, we evaluated locomotor SF for the femur in diverse lineages, including salamanders, frogs, turtles, lizards, crocodilians, and marsupials (opossums). Comparisons with values for hind-limb elements in running birds and eutherian mammals indicate phylogenetic diversity in limb-bone SF. A high SF (∼7) is primitive for tetrapods, but low magnitudes of load and elevated strength of bones contribute to different degrees across lineages; moreover, birds and eutherians appear to have evolved lower SFs independently. Second, we tested the hypothesis that SFs would be similar across limb bones within a taxon by comparing data from the humerus and femur of alligators. Both in bending and in torsion, we found a higher SF for the humerus than for the femur. Such a “mixed chain” of different SFs across elements has been predicted if bones have differing variabilities in load, different costs to maintain, or high SF values in general. Although variability in load is similar for the humerus and femur, a high SF may be less costly for the humerus because it is smaller than the femur. The high SFs of alligators also might facilitate differences in SF among their limb bones. Beyond these specific findings, however, a more general implication of our results is that evaluations of the diversity of limb-bone SFs can provide important perspective to direct future research. In particular, more complete understanding of variation in SF could provide insight into factors that promoted the evolutionary radiation of terrestrial locomotor function in vertebrates. [ABSTRACT FROM AUTHOR]

The American Society of Clinical Oncology and the College of American Pathologists have issued joint updated comprehensive guideline recommendations for human epidermal growth factor receptor 2 ( HER2) testing in breast cancer. The update not only provides guidelines for the test performance parameters, with the aim of improving test accuracy, reproducibility, and precision, but also provides comprehensive recommendations on the post-analytical interpretation of the results, and requires improved communication among healthcare providers. The updated guidelines are targeted at testing laboratories, pathologists, oncologists, surgeons, and, indirectly, other healthcare providers. Although the guidelines contribute to the improved analytical validity and clinical utility of laboratory assays required for successful molecularly targeted therapy in the era of personalized medicine, the implications of such recommendations have to be acknowledged. Certain recommendations, particularly those related to repeating the test and pathological concordance, have lower levels of supportive evidence than existing key recommendations, and the associated workload implications will be challenging to support in most healthcare systems. In this commentary, we critically address the key updated recommendations and their impact on service provision and patient care. [ABSTRACT FROM AUTHOR]