Five Key Articles on Curriculum Development for Graduate Medical Educators.

Background Curriculum development is an essential domain for medical educators, yet specific training in this area is inconsistent. With competing demands for educators' time, a succinct resource for best practice is needed. Objective To create a curated list of the most essential articles on curriculum development to guide education scholars in graduate medical education. Methods We used a modified Delphi method, a systematic consensus strategy to increase content validity, to achieve consensus on the most essential curriculum development articles. We convened a panel of 8 experts from the United States in curricular development, with diverse career stages, institutions, gender, and specialty. We conducted a literature search across PubMed and Google Scholar with keywords, such as "curriculum development" and "curricular design," to identify relevant articles focusing on a general overview or approach to curriculum development. Articles were reviewed across 3 iterative Delphi rounds to narrow down those that should be included in a list of the most essential articles on curriculum development. Results Our literature search yielded 1708 articles, 90 of which were selected for full-text review, and 26 of which were identified as appropriate for the modified Delphi process. We had a 100% response rate for each Delphi round. The panelists narrowed the articles to a final list of 5 articles, with 4 focusing on the development of new curriculum and 1 on curriculum renewal. Conclusions We developed a curated list of 5 essential articles on curriculum development that is broadly applicable to graduate medical educators.

Resident-led research: a quality improvement project to improve serious illness conversations.

Skilled conversations regarding end-of-life (EOL) care reduce emotional suffering and increase goal-concordant care. The Ariadne Labs Serious Illness Conversation (SIC) framework is an effective tool for improving EOL communication, but research is lacking on use with resident physicians. This study led by internal medicine residents tested the feasibility and acceptability of training peers in SIC. In 2021, three resident project leaders recruited first and second year internal medicine residents at a single tertiary academic center to receive extracurricular training on the Ariadne Labs SIC Guide. Baseline and post-training surveys were conducted to determine attitudes, barriers, and confidence related to EOL discussions. Initial recruitment efforts were unsuccessful but participation increased from zero to seven after residency administrators approved protected time for SIC training. Six residents (85.7%) completed baseline and post-training surveys. Residents identified lack of time as the key barrier to initiating SIC. Self-reported comfort discussing EOL care and documenting the conversations improved after training. Both resident researchers and participants reported SIC training was valuable and successful. Institutional support with dedicated buy-in, strong faculty mentorship, and committed resident leaders all contribute to successfully implementing a resident-led project.

Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

BACKGROUND: The prevalence of osteoporosis is increasing in the United States. PURPOSE: To evaluate low bone mass and osteoporosis treatments to prevent fractures. DATA SOURCES: Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. STUDY SELECTION: Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. DATA EXTRACTION: Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). DATA SYNTHESIS: We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). LIMITATION: Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. CONCLUSION: Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42021236220).

A temporal dependency feature in lower dimension for lung sound signal classification.

Respiratory sounds are expressed as nonlinear and nonstationary signals, whose unpredictability makes it difficult to extract significant features for classification. Static cepstral coefficients such as Mel-frequency cepstral coefficients (MFCCs), have been used for classification of lung sound signals. However, they are modeled in high-dimensional hyperspectral space, and also lose temporal dependency information. Therefore, we propose shifted [Formula: see text]-cepstral coefficients in lower-subspace (SDC-L) as a novel feature for lung sound classification. It preserves temporal dependency information of multiple frames nearby same to original SDC, and improves feature extraction by reducing the hyperspectral dimension. We modified EMD algorithm by adding a stopping rule to objectively select a finite number of intrinsic mode functions (IMFs). The performances of SDC-L were evaluated with three machine learning techniques (support vector machine (SVM), k-nearest neighbor (k-NN) and random forest (RF)) and two deep learning algorithms (multilayer perceptron (MLP) and convolutional neural network (cNN)) and one hybrid deep learning algorithm combining cNN with long short term memory (LSTM) in terms of accuracy, precision, recall and F1-score. We found that the first 2 IMFs were enough to construct our feature. SVM, MLP and a hybrid deep learning algorithm (cNN plus LSTM) outperformed with SDC-L, and the other classifiers achieved equivalent results with all features. Our findings show that SDC-L is a promising feature for the classification of lung sound signals.

Artificial intelligence model comparison for risk factor analysis of patent ductus arteriosus in nationwide very low birth weight infants cohort.

Despite the many comorbidities and high mortality rate in preterm infants with patent ductus arteriosus (PDA), therapeutic strategies vary depending on the clinical setting, and most studies of the related risk factors are based on small sample populations. We aimed to compare the performance of artificial intelligence (AI) analysis with that of conventional analysis to identify risk factors associated with symptomatic PDA (sPDA) in very low birth weight infants. This nationwide cohort study included 8369 very low birth weight (VLBW) infants. The participants were divided into an sPDA group and an asymptomatic PDA or spontaneously close PDA (nPDA) group. The sPDA group was further divided into treated and untreated subgroups. A total of 47 perinatal risk factors were collected and analyzed. Multiple logistic regression was used as a standard analytic tool, and five AI algorithms were used to identify the factors associated with sPDA. Combining a large database of risk factors from nationwide registries and AI techniques achieved higher accuracy and better performance of the PDA prediction tasks, and the ensemble methods showed the best performances.

Quantified assessment of hyperactivity in ADHD youth using IR-UWB radar.

Research on the quantification of hyperactivity in youth with attention-deficit/hyperactivity disorder (ADHD) has been limited and inconsistent. The purpose of this study was to test the discriminative value of impulse-radio ultra-wideband (IR-UWB) radar for monitoring hyperactive individuals with ADHD and healthy controls (HCs). A total of 10 ADHD patients and 15 HCs underwent hyperactivity assessment using IR-UWB radar during a 22-min continuous performance test. We applied functional ANOVA to compare the mean functions of activity level between the 2 groups. We found that the mean function of activity over time was significantly different and that the activity level of the ADHD group slightly increased over time with high dispersion after approximately 7 min, which means that the difference in activity level between the two groups became evident at this period. Further studies with larger sample sizes and longer test times are warranted to investigate the effect of age, sex, and ADHD subtype on activity level function.

Intraocular Pressure According to Eye Gaze by iCare Rebound Tonometry in Normal Participants and Glaucoma Patients.

PRECIS: We investigated changes of intraocular pressure (IOP) according to eye gaze. IOP was significantly elevated in adduction, abduction, and supraduction. However, there was no significant difference between glaucoma and control groups. PURPOSE: We assessed changes in IOP according to eye gaze and identified their correlations with various risk factors of glaucoma. PATIENTS AND METHODS: In this prospective observational study that included 56 glaucoma patients and 34 healthy participants, we measured IOP in the primary position with a Goldmann applanation tonometry and rebound tonometer. Then, this IOP was measured in abduction, adduction, supraduction using a rebound tonometer. IOP changes according to eye gaze were measured based on the baseline IOP, and IOP changes between glaucoma and the control groups were compared. Correlations between IOP changes and risk factors of glaucoma were evaluated. RESULTS: The baseline IOP was not significantly different between glaucoma and the control groups. Compared with the IOP in the primary position, a significant increase in IOP was 2.3±2.7 mm Hg during abduction (P<0.0001), 0.7±2.7 mm Hg during adduction (P<0.0001), and 1.2±2.8 mm Hg during supraduction (P<0.0001). However, there was no significant difference in the amount of IOP elevation or the ratio of IOP change between glaucoma and the control groups in all gazes. The baseline IOP measured by Goldmann applanation tonometry and IOP changes according to eye gaze showed a significant negative correlation in all gazes. CONCLUSIONS: IOP was significantly elevated in adduction, abduction, and supraduction than in the primary position in both the normal and glaucoma groups. However, there was no significant difference of IOP changes between glaucoma and normal groups.

Red cell manufacturing using parallel stirred-tank bioreactors at the final stages of differentiation enhances reticulocyte maturation.

The aim of this study was to develop a robust, quality controlled, and reproducible erythroid culture system to obtain high numbers of mature erythroblasts and red blood cells (RBCs). This was achieved using a fully controlled stirred-tank bioreactor by the design of experiments (DOE) methods in the serum-free medium by defining the appropriate culture parameters. Human cord blood CD34+ cells were first cultured in static flasks and then inoculated to stirred-tank bioreactors. Cell diameter was gradually decreased and final RBC yields were significantly higher when cells were inoculated at sizes smaller than 12 µm. The larger immature cells in the basophilic stage did not survive, while smaller mature erythroid cells were successfully expanded at high agitation speeds, demonstrating that appropriate seeding timing is critical. A high inoculation cell density of 5 × 106 cells/ml was achieved reaching 1.5 × 107 cells/ml. By using DOE analysis fitted to precise stages of erythropoiesis, we were able to acquire the optimal culture parameters for pH (7.5), temperature (37°C), dissolved oxygen, agitation speed (500 rpm), inoculation timing (cell diameter 12-13 µm), media feeding regimen, and cell seeding density (5 × 106 cells/ml). The final pure RBCs showed appropriate functions compared with fresh donor RBCs, confirming that manufacturing mature RBCs with reproducibility is possible.

Modified method for effective primary vascular smooth muscle progenitor cell culture from peripheral blood.

In previous studies, vascular smooth muscle progenitor cells (vSMPCs) isolated from peripheral blood mononuclear cells (PBMCs) were cultured using medium containing platelet-derived growth factor-BB (PDGF-BB) for 4 weeks. However, this method requires long culture periods of up to 4 weeks and yields low cell counts. Therefore, we proposed the modified method to improve the cell yield and purity and to reduce the cell culture period. PBMCs were isolated from human peripheral blood and cultured by the conventional method using medium containing PDGF-BB alone or the modified method using medium containing PDGF-BB, basic fibroblast growth factor (bFGF), and insulin-transferrin-selenium ITS for 4 weeks. The purity of vSMPCs was analyzed for the expression of a- smooth muscle actin (SMA) by flow cytometry and significantly higher in the modified method than conventional methods at the 1st and 2nd weeks. Also, mRNA expression of a-SMA by real-time PCR was significantly higher in the modified method than conventional method at the 2 weeks. The yield of vSMPCs by trypan blue exclusion assay was significantly higher in the modified method than conventional method at the 1st, 2nd and 3rd weeks. The primary culture using the modified method with PDGF-BB, bFGF, and ITS not only improved cell purity and yield, but also shortened the culture period, compared to the conventional culture method for vSMPCs. The modified method will be a time-saving and useful tool in various studies related to vascular pathology.

Role of Plasma Gelsolin Protein in the Final Stage of Erythropoiesis and in Correction of Erythroid Dysplasia In Vitro.

Gelsolin, an actin-remodeling protein, is involved in cell motility, cytoskeletal remodeling, and cytokinesis and is abnormally expressed in many cancers. Recently, human recombinant plasma gelsolin protein (pGSN) was reported to have important roles in cell cycle and maturation of primary erythroblasts. However, the role of human plasma gelsolin in late stage erythroblasts prior to enucleation and putative clinical relevance in patients with myelodysplastic syndrome (MDS) and hemato-oncologic diseases have not been reported. Polychromatic and orthochromatic erythroblasts differentiated from human cord blood CD34+ cells, and human bone marrow (BM) cells derived from patients with MDS, were cultured in serum-free medium containing pGSN. Effects of pGSN on mitochondria, erythroid dysplasia, and enucleation were assessed in cellular and transcriptional levels. With pGSN treatment, terminal maturation at the stage of poly- and ortho-chromatic erythroblasts was enhanced, with higher numbers of orthochromatic erythroblasts and enucleated red blood cells (RBCs). pGSN also significantly decreased dysplastic features of cell morphology. Moreover, we found that patients with MDS with multi-lineage dysplasia or with excess blasts-1 showed significantly decreased expression of gelsolin mRNA (GSN) in their peripheral blood. When BM erythroblasts of MDS patients were cultured with pGSN, levels of mRNA transcripts related to terminal erythropoiesis and enucleation were markedly increased, with significantly decreased erythroid dysplasia. Moreover, pGSN treatment enhanced mitochondrial transmembrane potential that is unregulated in MDS and cultured cells. Our findings demonstrate a key role for plasma gelsolin in erythropoiesis and in gelsolin-depleted MDS patients, and raises the possibility that pGSN administration may promote erythropoiesis in erythroid dysplasia.

Radiologic comparative analysis between saline and platelet-rich fibrin filling after hydraulic transcrestal sinus lifting without adjunctive bone graft: A randomized controlled trial.

OBJECTIVES: To evaluate implant survival rate, any complications, and changes in residual alveolar bone height (RABH) using saline or platelet-rich fibrin (PRF) filling after hydraulic transcrestal sinus lifting. METHODS: Dental implants were placed after hydraulic transcrestal sinus lifting and the filling of saline (20 patients) or PRF (20 patients). Outcome measurements were implant survival, any complications, and RABH changes. Cone-beam computed tomography (CBCT) scans were taken and compared preoperatively (T0), immediately postoperatively (T1), at 3 months (T2), 6 months (T3), and 12 months postoperatively (T4), respectively. RESULTS: In a total of 40 patients, 45 implants with a mean length of 10.4 ± 0.8 mm were placed in posterior maxilla of a mean RABH of 6.8 ± 1.1 mm. The increase in RABH peaked at T1, and continuous drooping of the sinus membrane was observed but stabilized at T3. Meanwhile, the gradual increase in the radiopacities was found below the lifted sinus membrane. The PRF filling induced the radiographic intrasinus bone gain of 2.6 ± 1.1 mm, which was significantly more than 1.7 ± 1.0 mm of saline filling at T4 (p < .05). All the implants were in function with no significant complications over the one-year follow-up period. CONCLUSIONS: In this randomized case-control study, the feasibility of hydraulic transcrestal sinus lifting without bone graft was confirmed and PRF might be a better filler to support the elevated sinus membrane. However, adjunctive bone grafting should still be indicated for cases requiring more than 2-3 mm of intrasinus bone gain.

Morphologic Characteristics and Clinical Significance of Computed Tomography and Magnetic Resonance Imaging Findings of Spinal Epidural Gas.

OBJECTIVE: To evaluate the morphologic characteristics and clinical significance of epidural gas based on computed tomography (CT) and magnetic resonance imaging (MRI) findings and to determine their relationship with radiculopathy. MATERIALS AND METHODS: Between March 2009 and November 2018, 110 epidural gas lesions were identified in 103 patients who underwent both CT and MRI for suspected herniated disc in the authors' institution. Patterns of epidural gas were classified as air pseudocyst, air cyst, air-contained disc herniation, and honeycomb-like air cyst. These gas patterns were compared, and possible correlations between these gas patterns and radiculopathy were evaluated. RESULTS: Overall agreement between CT and MRI findings for evaluation of all lesions and for differentiation of epidural gases was good (kappa [κ] = 0.775). Air pseudocysts demonstrated a moderate correlation (κ = 0.496) and air cysts showed a good correlation (κ = 0.661) with radiculopathy on MRI, whereas air-contained disc herniation and honeycomb-like cysts demonstrated a strong correlation (κ = 0.810 and 0.927, respectively) with radiculopathy on MRI. CONCLUSIONS: This study's results help delineate new classifications of epidural gases. In addition, lumbar epidural gas with disc material (e.g., air-contained disc herniation and honeycomb-like cysts) on MRI was associated with radiculopathy.

A rank weighted classification for plasma proteomic profiles based on case-based reasoning.

BACKGROUND: It is a challenge to precisely classify plasma proteomic profiles into their clinical status based solely on their patterns even though distinct patterns of plasma proteomic profiles are regarded as potential to be a biomarker because the profiles have large within-subject variances. METHODS: The present study proposes a rank-based weighted CBR classifier (RWCBR). We hypothesized that a CBR classifier is advantageous when individual patterns are specific and do not follow the general patterns like proteomic profiles, and robust feature weights can enhance the performance of the CBR classifier. To validate RWCBR, we conducted numerical experiments, which predict the clinical status of the 70 subjects using plasma proteomic profiles by comparing the performances to previous approaches. RESULTS: According to the numerical experiment, SVM maintained the highest minimum values of Precision and Recall, but RWCBR showed highest average value in all information indices, and it maintained the smallest standard deviation in F-1 score and G-measure. CONCLUSIONS: RWCBR approach showed potential as a robust classifier in predicting the clinical status of the subjects for plasma proteomic profiles.

Epidural Fluid Collection After Percutaneous Endoscopic Lumbar Discectomy.

OBJECTIVE: The frequency and extent of epidural fluid collection after percutaneous endoscopic lumbar discectomy (PELD) have not been previously described. The purpose of this study was to evaluate the significance of epidural fluid collection after PELD. METHODS: From March 2008 to November 2015, immediate postoperative magnetic resonance imaging (MRI) of 464 consecutive patients, comprising 284 men and 180 women, were obtained after PELD. The mean age of the patients at the time of admission was 43.1 years (range, 18-81 years). We also performed 24-hour follow-up MRIs after PELD in 35 patients to evaluate the morphologic changes on epidural fluid collection and to identify whether the collection was due to saline accumulation or cerebrospinal fluid leak. RESULTS: The level of disc herniation was at L4-5, L5-S1, L3-4, and L2-3 in 245 (52.8%), 173 (37.3%), 37 (8.0%), and 9 (1.9%) patients, respectively. Of 464 patients, 418 (90.1%) had abnormal epidural fluid collection, 404 (87.1%) patients had ventral epidural fluid collection, 393 (84.7%) patients had dorsal epidural fluid collection, and 10 patients had epidural hematoma as per immediate postoperative MRI. According to the 24-hour follow-up MRI findings, 30 patients had epidural fluid collection; the epidural fluid collection in 28 patients (93.3%) resolved with time, and a minimal amount of fluid remained in 2 patients, but the lesion size decreased compared with that on the previous day. CONCLUSIONS: Epidural fluid collection usually occurs after percutaneous endoscopic discectomy, which is mainly due to saline accumulation and typically resolves with time, without treatment or complications.

Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis.

OBJECTIVE: We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects. METHODS: We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model. RESULTS: At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036). CONCLUSION: The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time.

Relation Between Health-Related Quality of Life and Sleep Quality With Adjustment for Comorbidity Among the Korean Elderly: Mixed-Effects Model With a 6-Year Follow-up Study.

It is an important public health problem to identify risk factors of health-related quality of life (HRQoL) among the elderly. We recruited subjects from Ansan, Korea, as a subset of the Korean Genome and Epidemiology Study (KoGES), which is an ongoing population study, and followed up their sleep quality for 6 years. Mixed effect models were used to estimate the association between sleep quality and HRQoL, and we found that overall HRQoL was significantly lower to the elderly having poor sleep quality with adjustment for significant covariates although sleep quality showed a significant interaction effect with time for the mental component summary of SF-12. In particular, the elderly having lack of quality sleep appeared to have good general health, but their functional performances were significantly poor.

Human papillomavirus E7 serology and association with p16 immunohistochemistry in squamous cell carcinoma of the head and neck.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer is associated with improved survival and treatment response as compared to HPV-negative cancers. P16 overexpression is widely accepted as a surrogate marker for HPV positivity. METHODS: A total of 92 serum samples from 75 head and neck squamous cell carcinoma (HNSCC) patients were examined for HPV16 and 18 E7 antibodies by ELISA. Available tissue was tested for HPV-DNA by PCR, and p16 immunohistochemistry was obtained from a deidentified database. RESULTS: Of 75 HNSCC patients, 25 were HPV E7 seropositive. Seropositivity was strongly associated with cancers of the oropharynx, and correlated with positive p16 immunohistochemistry (IHC) and HPV-DNA. Post-treatment serum was available in a limited subset of patients, revealing a decrease in antibody titers following response to treatment. CONCLUSIONS: HPV E7 seropositivity correlated with positive tumor HPV-DNA and p16 expression, and was strongly associated with cancers of the oropharynx. E7 serology warrants further study as a potential biomarker in HPV-positive HNSCC.

The association between leukocyte telomere lengths and sleep instability based on cardiopulmonary coupling analysis.

PURPOSE: The purpose of the study is to examine the objective association between sleep stability and leukocyte telomere lengths (LTL) using cardiopulmonary coupling (CPC) analysis, which is an electrocardiogram (ECG)-based technique to quantify physiologic sleep stability. METHODS: Three hundred eighty-one healthy subjects were recruited from a community-based cohort study from the Korean Genome and Epidemiology Study (KoGES), and the associations between LTL and total quantities of different frequency coupling bands were examined using generalized linear model (GLM) with adjustment of significant covariates. RESULTS: LTL showed a significant association with elevated narrow-band low frequency coupling (e-LFCNB, a CPC marker of periodic breathing or sleep fragmentation due to pathological respiratory chemoreflex activation) by interacting with obstructive sleep apnea (OSA) severity (p value of <0.0001). Especially, sleep stability significantly reduced with shortened LTL in OSA patients (Apnea-Hypopnea Index (AHI) ≥15) based on increased e-LFCNB which had a negative correlation with high-frequency coupling band (HFC), a marker of stable sleep. CONCLUSION: The present study suggested that shorter LTL might contribute to reduced sleep stability by interacting with OSA severity due to the stress of chronic sleep fragmentation or invariant sympathetic activity by respiratory chemoreflex activation.

Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer.

Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV's possible etiologic link to NSCLC by evaluating an immune response to HPV's oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC.

Casares' map function: no need for a 'corrected' Haldane's map function.

A genetic map function M(d) = RF provides a mapping from the additive genetic distance d to the non-additive recombination fraction RF between a given pair of loci, where the recombination fraction is the proportion of gametes that are recombinant between the two loci. Genetic map functions are needed because in most experiments all we can directly observe are the recombination events. However, since a recombination event is only observed if there are an odd number of crossovers between the two loci, recombination fractions are not additive. One of the most widely used map functions is Haldane's map function, which is derived under the assumptions of no chiasma and no chromatid interference, and has been in widespread use since 1919. However, Casares recently proposed a 'corrected' Haldane's map function - we show here that this 'corrected' map function is not correct due to faulty assumptions and mistakes in its derivation.