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Prehabilitation is well established for improving outcomes in cancer surgery. Combining prehabilitation with neoadjuvant treatments may provide an opportunity to rapidly initiate cancer-directed therapy while improving functional status in preparation for local consolidation. In this proof-of-concept study, we analyzed non-small-cell lung cancer patients who underwent simultaneous prehabilitation and neoadjuvant therapy.We retrospectively analyzed all patients who underwent neoadjuvant treatment for non-small-cell lung cancer followed by curative intent surgery between 2015 and 2021. Patients who were screened for the prehabilitation program were identified. The screening included assessment of physical performance, nutritional status, and signs of anxiety and depression.We identified a total of 141 patients who underwent neoadjuvant therapy. Twenty patients were screened to undergo a prehabilitation program. Four patients did not complete the exercise program (1 surgical intervention too soon, 1 drop-out after the first session, and 2 patients were deemed fit without intervention). The postoperative median length of stay was 2 days (range 1-18). Patients improved their 6-minute-walk test despite undergoing neoadjuvant treatment by a mean of 33 meters (± 50, P = .1). Self-reported functional status (DASI) showed significant improvement by a mean of 10 points (± 11, P = .03), and HADS-anxiety-score was significantly reduced after the prehabilitation program by a mean of 1.5 points (± 1, P = .005).Neoadjuvant prehabilitation therapy is feasible and associated with encouraging results. The performance of all measures remains a logistic challenge. With multimodal strategies for lung cancer treatment becoming key to optimal outcomes, neoadjuvant prehabilitation therapy is a concept worthy of prospective multi-center evaluation.

Background Anti-PD-1 has activity in brain metastases (BM). This phase II open labeled non-randomized single arm trial examined the safety and efficacy of combining nivolumab with radiosurgery (SRS) in the treatment of patients with BM from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Methods This was a multicenter trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated BM and no prior immunotherapy were eligible. Nivolumab (240 mg or 480 mg IV) was administered for up to 2 years until progression. SRS (15–21 Gy) to all un-irradiated BM was delivered within 14 days after the first dose of nivolumab. The primary endpoint was intracranial progression free survival (iPFS). Results Twenty-six patients (22 NSCLC and 4 RCC) were enrolled between August 2017 and January 2020. A median of 3 (1–9) BM were treated with SRS. Median follow-up was 16.0 months (0.43–25.9 months). Two patients developed nivolumab and SRS related grade 3 fatigue. One-year iPFS and OS were 45.2% (95% CI 29.3–69.6%) and 61.3% (95% CI 45.1–83.3%), respectively. Overall response (partial or complete) of SRS treated BM was attained in 14 out of the 20 patients with ≥1 evaluable follow-up MRI. Mean FACT-Br total scores were 90.2 at baseline and improved to 146.2 within 2–4 months (P = .0007). Conclusions The adverse event profile and FACT-Br assessments suggested that SRS during nivolumab was well tolerated. Upfront SRS with the initiation of anti-PD-1 prolonged the 1-year iPFS and achieved high intracranial control. This combined approach merits validation randomized studies.

Scott Owen,1 Scheryll Alken,2,3 Jad Alshami,1 Marie-Christine Guiot,1,4 Petr Kavan,1 David A Reardon,5 Thierry Muanza,1,4,6 Neil Gibson,7 Karine Pemberton,8 Flavio Solca,9 Agnieszka Cseh10 ,†Frank Saran2,11 1Clinical Research Unit, Montreal Neurological Institute and Hospital, McGill University Health Center, Montreal, Canada; 2Radiation Oncology Unit, Royal Marsden Hospital, London, UK; 3St James’s Hospital, Dublin, Ireland; 4Neuropathology Division, Montreal Neurological Institute and Hospital, McGill University Health Center, Montreal, Canada; 5Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; 6Radiation Oncology, Jewish General Hospital, Montreal, Canada; 7Drug Metabolism & Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 8Medical Department, Boehringer Ingelheim Ltd., Bracknell, UK; 9Department of Pharmacology, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 10Department of Medical Affairs, Boehringer Ingelheim International, Ingelheim am Rhein, Germany; 11Department of Blood and Cancer, Auckland City Hospital, Auckland, New Zealand†Agnieszka Cseh passed away in May 2021Correspondence: Frank Saran, Auckland City Hospital, Cancer and Blood Service, Building 8, 99 Park Road, Grafton, Private Bag 92024, Auckland, 1142, New Zealand, Tel +64 09 623 6046, Email FSaran@adhb.govt.nzAbstract: Glioblastoma is an aggressive form of central nervous system tumor. Recurrence rates following primary therapy are high, and few second-line treatment options provide durable clinical benefit. Aberrations of the epidermal growth factor receptor (EGFR) gene are observed in up to 57% of glioblastoma cases and EGFR overexpression has been identified in approximately 60% of primary glioblastomas. In preclinical studies, afatinib, a second-generation ErbB blocker, inhibited cell proliferation in cells harboring mutations commonly found in glioblastoma. In two previous Phase I/II studies of afatinib plus temozolomide in patients with glioblastoma, limited efficacy was observed; however, there was notable benefit in patients with the EGFR variant III (EGFRvIII) mutation, EGFR amplification, and those with loss of phosphatase and tensin homolog (PTEN). This case series report details treatment histories of three long-term responders from these trials. Next-generation sequencing of tumor samples identified alterations in a number of cancer-related genes, including mutations in, and amplification of, EGFR. Tumor samples from all three patients shared favorable prognostic factors, eg O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter methylation; however, negative prognostic factors were also observed, suggesting that these shared genetic features did not completely account for the favorable responses. The genetic profile of the tumor from Patient 1 showed clear differences from the other two tumors: lack of involvement of EGFR aberrations but with a mutation occurring in PTPN11. Preclinical studies showed that single-agent afatinib and temozolomide both separately inhibit the growth of tumors with a C-terminal EGFR truncation, thus providing further rationale for combining these two agents in the treatment of glioblastomas harboring EGFR aberrations. These findings suggest that afatinib may provide treatment benefit in patients with glioblastomas that harbor ErbB family aberrations and, potentially, other genetic aberrations. Further studies are needed to establish which patients with newly diagnosed/recurrent glioblastomas may potentially benefit from treatment with afatinib.Keywords: next-generation sequencing, long-term response, EGFR, genetic aberrations

Objective Techniques for reconstruction of skull base defects have advanced greatly since the introduction of the vascular pedicled nasoseptal flap in 2006. The objective of this review is to assess the current state of the field by examining both intranasal and extranasal techniques of vascular pedicled skull base defect repair, their indications and success rates, and novel techniques that are currently under investigation. Methods A review of the literature describing the use of vascular pedicled flaps in skull base defect reconstruction was conducted using PubMed and Google Scholar. Results The nasoseptal flap remains the most widely used vascular pedicled flap for endoscopic repair of skull base defects. Its ease of harvest, wide arch of rotation, and high success rates make it a popular choice among surgeons. Several variations including a “rescue” nasopseptal flap have been developed. Other less commonly used pedicled intranasal flaps include the middle turbinate flap and the posterior pedicled inferior turbinate flap. Additionally, several novel vascular pedicled flaps have been developed and tested in small cohorts of patients. Extranasal flaps such as the pericranial flap and the temporoparietal fascia flap are used less frequently than intranasal flaps. However, they remain valuable options for reconstruction in certain situations. Conclusion Advancements continue to be made in the field of skull base defect reconstruction using vascular pedicled flaps. Though the nasoseptal flap remains the most widely utilized option, additional intranasal techniques continue to be developed and tested to optimize surgical outcomes and patient care. Level of Evidence NA, Endoscopic reconstruction of skull base defects has rapidly advanced since the introduction of the nasoseptal flap in 2006. Here, we review current techniques of vascular pedicled flap reconstruction of skull base defects, their indications and success rates, and novel techniques currently under investigation.

Using data obtained from 51 male and 133 female undergraduates enrolled in six classes in educational psychology, the authors obtained evidence supporting the existence of slight sex differences in descriptions or appraisals of instruction and also suggesting a relationship between the overall past achievement of the males and their perceptions of the quality of classroom interpersonal relations. No relationships were found between students' life histories and their perceptions of instruction or between their level of creativity and perceptions of instruction. These results support some previous studies cited and do not support others, also cited. This study lends some support to those who question the internal validity of the claim that differences in students' perceptions of instruction necessarily reflect differences in the effectiveness of instruction. (Author)

Decellularization is one of the promising techniques in tissue engineering used to create a biological scaffold for subsequent repopulation with the patient’s own cells. This study aims to compare two different decellularization protocols to optimize the process of auricle decellularization by assessing and characterizing the decellularization effects on human auricular cartilage. Herein, 12 pairs (8 females, 4 males) of freshly frozen adult human cadaveric auricles were de-epithelialized and defatted leaving only the cartilaginous framework. An auricle from each pair was randomly assigned to either protocol A (latrunculin B-based decellularization) or protocol B (trypsin-based decellularization). Gross examination of the generated scaffolds demonstrated preservation of the auricles’ contours and a change in color from pinkish-white to yellowish-white. Hematoxylin and eosin staining demonstrated empty cartilaginous lacunae in both study groups, which confirms the depletion of cells. However, there was greater preservation of the extracellular matrix in auricles decellularized with protocol A as compared to protocol B. Comparing protocol A to protocol B, Masson’s trichrome and Safranin-O stains also demonstrated noticeable preservation of collagen and proteoglycans, respectively. Additionally, scanning electron micrographs demonstrated preservation of the cartilaginous microtopography in both study groups. Biomechanical testing demonstrated a substantial decrease in Young’s modulus after decellularization using protocol B (1.3 MPa), albeit not significant (P-value > 0.05) when compared to Young’s modulus prior to decellularization (2.6 MPa) or after decellularization with protocol A (2.7 MPa). A DNA quantification assay demonstrated a significant drop (P-value < 0.05) in the DNA content after decellularization with protocol A (111.0 ng/mg) and protocol B (127.6 ng/mg) in comparison to before decellularization (865.3 ng/mg). Overall, this study demonstrated effective decellularization of human auricular cartilage, and it is concluded that protocol A provided greater preservation of the extracellular matrix and biomechanical characteristics. These findings warrant proceeding with the assessment of inflammation and cell migration in a decellularized scaffold using an animal model.

Pupil perceptions of significant aspects of the instruction of student teachers of English and the indication of ways in which these perceptions may be used in evaluation are presented in this study. Data were obtained at the University of Georgia for student teachers of English who student taught during the winter and fall quarter 1969 and the winter quarter 1971. The class each student teacher had taught the most was tested one week after the student teacher had left. Pupils were asked to respond to a 74-item Inventory of Student Perceptions of Instruction (ISPI). The frame of reference was the instruction carried out by the student teacher. The ISPI was concerned with six aspects of student perception: instructional objectives, classroom human relations, use of instructional resources, student motivation for learning, meaningfulness of learning, and measurement and evaluation. Students were asked to read each item on the ISPI carefully and express a degree of agreement or disagreement. Results of the inventory indicate four evaluation uses: student teacher self-evaluation, cooperative student teacher evaluation participated in by the student teacher, supervising teacher selection, and appraisal of the program to prepare student teachers. A five-item bibliography, figures and appendixes with inventories are included. (MJM)

The 1955 check-list consisted of 92 items giving students' perceptions of the teaching-learning process, and was suggested for use in teacher self-evaluation. It was revised in the spring of 1969 to incorporate results of recent research and to apply specifically to classes in high school English. Similar devices, together with articles and books on research in classroom learning were reviewed for item content and construct validity. Wording was simplfied: each specification was limited, where practicable, to a single concept; and classifications were clarified, resulting in an increase from 28 to 34 specifications. The type of response was changed from frequency-of-occurrence to degree-of-occurrence to degree-of-agreement and the list tested in 16 classes Alpha coefficients were obtained for section scores as well as for total scores, and correlational data suggested that both scores were useful. The construct validity was investigated through factor analysis and revealed the check-list to be a multi-dimensional instrument. It was concluded that (1) reliability of response was higher on observable than on inferred behavior, (2) items not understood should be given a neutral score, and (3) factor analytic results did not contribute to interpreting responses. The revised specifications and list of categorized items are attached. (MBM)

The purpose of this investigation was to examine the performance of University of Georgia student teachers in English on the six dimensions of the Checklist of High School Class Activities and to compare this evaluation with student teaching grades, academic grades, and scores on the National Teacher Examinations. The 74-item checklist was administered to the pupils in one class of each of 16 secondary school English student teachers at the end of one quarter, with classes of exceptionally high or low ability being eliminated. Although there was great variability in individual scores, the student teachers as a group tended to be highly rated by their pupils. These ratings, however, showed no significant correlation with student teaching grades, academic grades, or National Teacher Examination scores. Results indicate that pupil perception of a teacher's performance tends to differ from that of other evaluation sources. (An appendix contains the specifications for the checklist and a categorized list of the 74 checklist items.) (RT)

TO SURVEY THE CERTIFICATION STATUS, TEACHING ASSIGNMENT, AND SELECTED JOB-RELATED OPINIONS OF GEORGIA SOCIAL STUDIES TEACHERS, DATA ON 115 SCHOOLS AND 403 TEACHERS WAS EXTRACTED FROM A RANDOM SAMPLING OF THE ANNUAL REPORTS OF SCHOOL SUPERINTENDENTS TO THE GEORGIA ACCREDITING COMMISSION. AN UNSTRUCTURED QUESTIONNAIRE ASKING WHICH ASPECTS OF TEACHING THEY FOUND MOST DIFFICULT AND MOST SATISFYING WAS THEN SENT TO THE 278 TEACHERS WHO WERE STILL TEACHING IN THE SAME SCHOOL. 192 RESPONDED. IT WAS FOUND THAT (1) 92 PERCENT OF THE TEACHERS HAD A PROFESSIONAL CERTIFICATE, 6 PERCENT HAD A PROVISIONAL CERTIFICATE, 1 PERCENT AN EMERGENCY CERTIFICATE, AND 1 PERCENT ANOTHER PROFESSIONAL CERTIFICATE. (2) 46 PERCENT TAUGHT ONE SOCIAL STUDIES SUBJECT, 44 PERCENT TAUGHT TWO, AND 9.5 PERCENT TAUGHT FOUR OR MORE. (3) THE SUBJECTS RATED MOST POPULAR BY GEORGIA TEACHERS WERE NEARLY THE SAME AS THOSE RANKED MOST POPULAR IN THE SOUTH AND THE NATION IN A 1963 EDUCATIONAL TESTING SERVICE SURVEY. (4) THE ASPECTS OF TEACHING RATED MOST DIFFICULT WERE MOTIVATING STUDENTS, PERFORMING ADMINISTRATIVE DUTIES, TEACHING COMPLEX COGNITIVE SKILLS, AND CONTROLLING STUDENT BEHAVIOR. (5) HELPING STUDENTS LEARN, SATISFACTION DEPRIVED FROM THE LATER SUCCESS OF FORMER STUDENTS, ASSOCIATING WITH YOUNG PEOPLE, AND BECOMING A BETTER TEACHER WERE THE MOST SATISFYING ASPECTS OF TEACHING. (AW)

IMPORTANCE: Numerous techniques are used for septal perforation repair, yet success rates remain variable. Few studies have evaluated the effectiveness of interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft for septal perforation repair. OBJECTIVE: To investigate and describe the use of interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft for septal perforation repair and the expansion of this technique to patients with more challenging comorbidities, including granulomatosis with polyangiitis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical record review was performed of patients who underwent septal perforation repair using interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft from January 1, 2015, to July 1, 2018, at Vanderbilt University Medical Center and from January 1, 2017, to July 1, 2018, at the University of Iowa. INTERVENTION: All patients underwent septal perforation repair with interposition grafts of polydioxanone plates and a temporoparietal fascia graft. MAIN OUTCOMES AND MEASURES: Assessing closure of septal perforation was the primary outcome. Secondary outcomes were resolution of presenting symptoms of septal perforation, area of perforation, length of postoperative stent and silastic sheeting placement, postoperative complications and resolution, and duration of follow-up. Preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) scores were assessed. RESULTS: A total of 17 patients (12 women and 5 men; mean [SD] age, 45 [15] years) were included. The causes of perforations were iatrogenic (9 [53%]), rheumatologic (2 [12%]), and unknown or idiopathic (6 [35%]). Patients most commonly presented with nasal crusting (12 [71%]), whistling (9 [53%]), nasal obstruction (9 [53%]), and epistaxis (5 [29%]). Mean (SD) perforation size was 0.99 (1.04) cm(2). Mean (SD) postoperative follow-up was 6.1 (4.1) months. A total of 15 patients (88%) had complete resolution of presenting symptoms at last follow-up. All perforations were closed with overlying mucosa at the most recent follow-up examination. Nine of 17 patients completed both preoperative and postoperative NOSE. There was a significant difference between the mean (SD) preoperative and postoperative NOSE scores (62.78 [27.74] vs 17.78 [15.83]; P = .004). CONCLUSIONS AND RELEVANCE: Repair of symptomatic nasal septal perforations using a temporoparietal fascia graft combined with a polydioxanone plate was associated with positive outcomes. Repair of septal perforations caused by rheumatologic disease, including granulomatosis with polyangiitis, can be considered for repair using this technique. Resolution of symptoms appeared to be clinically more meaningful in evaluation of septal perforation repair than rate of perforation closure, and the NOSE scale has the potential to serve as an objective corroboration to patient-reported postoperative outcomes. LEVEL OF EVIDENCE: 4.

To examine trend, prevalence, and outcomes of surgical site infection (SSI) in head and neck surgery.Retrospective cross-sectional analysis.The Nationwide Readmissions Database (2010-2014), which represents 56.6% of all US hospitalization.Adult patients (≥18 years) who underwent head and neck surgery. Patients with SSI were compared with controls.Analysis included chi-square test and multivariate logistic and linear regression models.A total of 427 cases and 116,921 controls were identified. SSI prevalence among patients who underwent head and neck surgery was 0.37%, of which 41.0% was reported within the initial admission while the remaining 59.0% was reported on readmission within 30 days of first surgery. SSI was associated with a higher mortality risk (odds ratio, 3.95; 95% CI, 1.25-12.50;SSI is associated with a significant mortality risk and burden on the health system. More than half of SSI cases were identified on readmission.

Left-Wing Authoritarianism (LWA) has a controversial history in psychology. Some researchers have expressed skepticism about the existence of LWA, whereas others have argued that LWA is a valid construct. In the present article, we offer a framework to reconcile these two perspectives by proposing that ideologically-based authoritarian norms are sometimes in conflict with the processes that create authoritarian individuals. In Western political contexts, authoritarian norms are more likely to occur on the conservative side of the political spectrum; but authoritarian persons can occur in both conservatives and liberals. In our model, left-wing authoritarians thus often occupy the space where forces influencing authoritarianism are in conflict. We review existing evidence related to the model, derive four hypotheses from the model, and discuss criteria for falsifying the model. We conclude by considering the model’s place in current research on the complexities of ideology.