Sex-specific splicing of Z- and W-borne nr5a1 alleles suggests sex determination is controlled by chromosome conformation.

Pogona vitticeps has female heterogamety (ZZ/ZW), but the master sex-determining gene is unknown, as it is for all reptiles. We show that nr5a1 (Nuclear Receptor Subfamily 5 Group A Member 1), a gene that is essential in mammalian sex determination, has alleles on the Z and W chromosomes (Z-nr5a1 and W-nr5a1), which are both expressed and can recombine. Three transcript isoforms of Z-nr5a1 were detected in gonads of adult ZZ males, two of which encode a functional protein. However, ZW females produced 16 isoforms, most of which contained premature stop codons. The array of transcripts produced by the W-borne allele (W-nr5a1) is likely to produce truncated polypeptides that contain a structurally normal DNA-binding domain and could act as a competitive inhibitor to the full-length intact protein. We hypothesize that an altered configuration of the W chromosome affects the conformation of the primary transcript generating inhibitory W-borne isoforms that suppress testis determination. Under this hypothesis, the genetic sex determination (GSD) system of P. vitticeps is a W-borne dominant female-determining gene that may be controlled epigenetically.

What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma?

PURPOSE AND DESIGN: Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett's esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC. METHODS: The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements "Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC" and "Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC". Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system. RESULTS AND CONCLUSIONS: In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.

Anchoring genome sequence to chromosomes of the central bearded dragon (Pogona vitticeps) enables reconstruction of ancestral squamate macrochromosomes and identifies sequence content of the Z chromosome.

BACKGROUND: Squamates (lizards and snakes) are a speciose lineage of reptiles displaying considerable karyotypic diversity, particularly among lizards. Understanding the evolution of this diversity requires comparison of genome organisation between species. Although the genomes of several squamate species have now been sequenced, only the green anole lizard has any sequence anchored to chromosomes. There is only limited gene mapping data available for five other squamates. This makes it difficult to reconstruct the events that have led to extant squamate karyotypic diversity. The purpose of this study was to anchor the recently sequenced central bearded dragon (Pogona vitticeps) genome to chromosomes to trace the evolution of squamate chromosomes. Assigning sequence to sex chromosomes was of particular interest for identifying candidate sex determining genes. RESULTS: By using two different approaches to map conserved blocks of genes, we were able to anchor approximately 42 % of the dragon genome sequence to chromosomes. We constructed detailed comparative maps between dragon, anole and chicken genomes, and where possible, made broader comparisons across Squamata using cytogenetic mapping information for five other species. We show that squamate macrochromosomes are relatively well conserved between species, supporting findings from previous molecular cytogenetic studies. Macrochromosome diversity between members of the Toxicofera clade has been generated by intrachromosomal, and a small number of interchromosomal, rearrangements. We reconstructed the ancestral squamate macrochromosomes by drawing upon comparative cytogenetic mapping data from seven squamate species and propose the events leading to the arrangements observed in representative species. In addition, we assigned over 8 Mbp of sequence containing 219 genes to the Z chromosome, providing a list of genes to begin testing as candidate sex determining genes. CONCLUSIONS: Anchoring of the dragon genome has provided substantial insight into the evolution of squamate genomes, enabling us to reconstruct ancestral macrochromosome arrangements at key positions in the squamate phylogeny, demonstrating that fusions between macrochromosomes or fusions of macrochromosomes and microchromosomes, have played an important role during the evolution of squamate genomes. Assigning sequence to the sex chromosomes has identified NR5A1 as a promising candidate sex determining gene in the dragon.

CD151 Gene and Protein Expression Provides Independent Prognostic Information for Patients with Adenocarcinoma of the Esophagus and Gastroesophageal Junction Treated by Esophagectomy.

BACKGROUND: Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis. METHODS: Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx)-naïve patients with external validation in a separate cohort of 62 CRTx-naïve patients and 169 patients with advanced-stage disease treated with CRTx. RESULTS: As a novel prognostic biomarker after external validation, CD151 showed promise. Patients exhibiting high levels of CD151 (≥median) had a longer median overall survival than patients with low CD151 tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox-regression model with adjustment for tumor stage [adjusted hazard ratio (aHR), 0.33; 95 % confidence interval (CI), 0.14-0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR, 0.22; 95 % CI, 0.08-0.59; p = 0.003). This effect was not found in the separate cohort of CRTx-exposed patients. CONCLUSION: Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone.

Retrospective stable isotope analysis reveals ecosystem responses to river regulation over the last century.

Disruption of natural flow regimes, nutrient pollution, and other consequences of human population growth and development have impacted most major rivers of the world. Alarming losses of aquatic biodiversity coincide with human-caused river alteration, but effects of biotic homogenization on aquatic ecosystem processes are not as well documented. This is because unaltered systems for comparison are scarce, and some ecosystem-wide effects may take decades to manifest. We evaluated aquatic ecosystem responses to extensive river- floodplain engineering and nutrient addition in the Rio Grande of southwestern North America as revealed by changes in trophic structure of, and resource availability to, the fish community. Stable Isotope Analysis (SIA) was conducted on museum-preserved fishes collected over a 70-year period of intensive river management and exponential human population growth. Trophic complexity and resource heterogeneity for fish consumers (measured as "isotopic niche breadth") decreased following sediment deprivation and channelization, and these effects persist into the present. Increased nutrient inputs led to δ15N enrichment in the entire fish community at all affected sites, and a shift to autochthonous sources of carbon at the most proximal site downstream of wastewater release, probably via bottom-up transfer. Overall, retrospective SIA of apex consumers suggests radical change and functional impairment of a floodplain river ecosystem already marked by significant biodiversity loss.

Frequent callers to the ambulance service: patient profiling and impact of case management on patient utilisation of the ambulance service.

BACKGROUND: A minority of patients make frequent and excessive calls to the ambulance service, placing a significant burden on limited resources at a time when demand on urgent and emergency care systems is steadily increasing. Little is known about the reasons underlying frequent caller behaviour or the best way to manage this group of patients. OBJECTIVES: The present study aimed to (i) profile frequent callers to the ambulance service and (ii) evaluate the impact of a case management interventional approach on frequent caller behaviour. METHODS: A retrospective review of data from a 2-year period (from 1 April 2009 to 31 March 2011) was conducted. Patients were included in the analysis if they had been accepted for case management intervention by the Patient-Centred Action Team during this period and met the study inclusion criteria. RESULTS: The review identified 110 frequent callers who met the study inclusion criteria. The majority of frequent callers (86%) had multiple and complex reasons for calling, including frequent medical need, acute or chronic mental health condition, older age and unmet personal or social care needs. In the majority of cases (82%), multiple interventional strategies were required. A significant reduction in median call volume was observed from preintervention to postintervention (from five calls/month to zero calls/month). CONCLUSIONS: Effective management of this complex patient group requires an individualised case management approach in order to identify and tackle the underlying causes of behaviour.

The Impact of Racial Disparities and the Social Determinants of Health on Esophageal and Gastric Cancer Outcomes.

Reducing long-standing inequities in gastric and esophageal cancers is a priority of patients, providers, and policy makers. Many social determinants of health influence risk factors for disease development, incidence, treatment, and outcomes of gastric and esophageal cancers.

Real-World Health Care Resource Use and Costs Among Patients With Chronic Lymphocytic Leukemia Treated With Venetoclax-Based and Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Second-Line Setting.

PURPOSE: Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. METHODS: This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). RESULTS: Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). CONCLUSION: Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

Does use of the recognition of stroke in the emergency room stroke assessment tool enhance stroke recognition by ambulance clinicians?

BACKGROUND AND PURPOSE: U.K ambulance services assess patients with suspected stroke using the Face Arm Speech Test (FAST). The Recognition Of Stroke In the Emergency Room (ROSIER) tool has been shown superior to the FAST in identifying strokes in emergency departments but has not previously been tested in the ambulance setting. We investigated whether ROSIER use by ambulance clinicians can improve stroke recognition. METHODS: Ambulance clinicians used the ROSIER in place of the FAST to assess patients with suspected stroke. As the ROSIER includes all FAST elements, we calculated a FAST score from the ROSIER to enable comparisons between the two tools. Ambulance clinicians' provisional stroke diagnoses using the ROSIER and calculated FAST were compared with stroke consultants' diagnosis. We used stepwise logistic regression to compare the contribution of individual ROSIER and FAST items and patient demographics to the prediction of consultants' diagnoses. RESULTS: Sixty-four percent of strokes and 78% of nonstrokes identified by ambulance clinicians using the ROSIER were subsequently confirmed by a stroke consultant. There was no difference in the proportion of strokes correctly detected by the ROSIER or FAST with both displaying excellent levels of sensitivity. The ROSIER detected marginally more nonstroke cases than the FAST, but both demonstrated poor specificity. Facial weakness, arm weakness, seizure activity, age, and sex predicted consultants' diagnosis of stroke. CONCLUSIONS: The ROSIER was not better than the FAST for prehospital recognition of stroke. A revised version of the FAST incorporating assessment of seizure activity may improve stroke identification and decision making by ambulance clinicians.

Sequence and gene content of a large fragment of a lizard sex chromosome and evaluation of candidate sex differentiating gene R-spondin 1.

BACKGROUND: Scant genomic information from non-avian reptile sex chromosomes is available, and for only a few lizards, several snakes and one turtle species, and it represents only a small fraction of the total sex chromosome sequences in these species. RESULTS: We report a 352 kb of contiguous sequence from the sex chromosome of a squamate reptile, Pogona vitticeps, with a ZZ/ZW sex microchromosome system. This contig contains five protein coding genes (oprd1, rcc1, znf91, znf131, znf180), and major families of repetitive sequences with a high number of copies of LTR and non-LTR retrotransposons, including the CR1 and Bov-B LINEs. The two genes, oprd1 and rcc1 are part of a homologous syntenic block, which is conserved among amniotes. While oprd1 and rcc1 have no known function in sex determination or differentiation in amniotes, this homologous syntenic block in mammals and chicken also contains R-spondin 1 (rspo1), the ovarian differentiating gene in mammals. In order to explore the probability that rspo1 is sex determining in dragon lizards, genomic BAC and cDNA clones were mapped using fluorescence in situ hybridisation. Their location on an autosomal microchromosome pair, not on the ZW sex microchromosomes, eliminates rspo1 as a candidate sex determining gene in P. vitticeps. CONCLUSION: Our study has characterized the largest contiguous stretch of physically mapped sex chromosome sequence (352 kb) from a ZZ/ZW lizard species. Although this region represents only a small fraction of the sex chromosomes of P. vitticeps, it has revealed several features typically associated with sex chromosomes including the accumulation of large blocks of repetitive sequences.

The Ability of Self-Report Methods to Accurately Diagnose Attention Deficit Hyperactivity Disorder: A Systematic Review.

OBJECTIVE: To identify and analyze all studies validating rating scales or interview-based screeners commonly used to evaluate ADHD in adults. METHOD: A systematic literature search identified all studies providing diagnostic accuracy statistics, including sensitivity and specificity, supplemented by relevant articles or test manuals referenced in reviewed manuscripts. RESULTS: Only 20 published studies or manuals provided data regarding sensitivity and specificity when tasked with differentiating those with and without ADHD. While all screening measures have excellent ability to correctly classify non-ADHD individuals (with negative predictive values exceeding 96%), false positive rates were high. At best, positive predictive values in clinical samples reached 61%, but most fell below 20%. CONCLUSION: Clinicians cannot rely on scales alone to diagnose ADHD and must undertake more rigorous evaluation of clients who screen positive. Furthermore, relevant classification statistics must be included in publications to help clinicians make statistically defensible decisions. Otherwise, clinicians risk inappropriately diagnosing ADHD.

Short-Term Outcomes of COVID-19 Pandemic on Non-Small Cell Lung Cancer Screening and Management.

Background To assess the impact of coronavirus disease 2019 (COVID-19) pandemic on non-small cell lung cancer (NSCLC) screening, staging, and management in a single health care system. Materials and Methods From November 2015 to December 2020, a total of 1,547 NSCLC cases was reported at our institution including 1,329 cases pre-COVID-19 and 218 cases during COVID-19. Pre-COVID-19 was defined as November 2015 to February 2020, while during COVID-19 was March 2020 to December 2020. Data were collected from tumor registry and medical record review. Patients with mesothelioma, lymphoma, small cell, or mixed small cell cancer were excluded from the study. Results Both pre-COVID-19 and during COVID-19 cohorts had similar comorbidities including age (70 vs. 71 years), current smokers (35 vs. 32%), and chronic obstructive lung disease (32 vs. 28%). The number of low-dose computed tomography lung cancer screening scans decreased by 25% during COVID-19 compared with pre-COVID-19 era. There were more cases of stage 1A NSCLC pre-COVID-19 (31 vs. 25%) and more stage 4 cancer during COVID-19 (42 vs. 33%); p = 0.01. The proportion of patients treated with radiotherapy was similar between pre-COVID-19 and during COVID-19 (49 vs. 50%), but fewer patients underwent surgery during COVID-19 (17 vs. 27%; p = 0.004). The median time to radiotherapy (67 days) and surgery (29 days) was similar between the groups. The unadjusted overall 6-month mortality after lung cancer diagnoses was higher during COVID-19 compared with pre-COVID-19 (28 vs. 22%; p = 0.04). Conclusion The COVID-19 pandemic resulted in delayed lung cancer screening scans, and more patients had diagnosis of advanced NSCLC; however, short-term mortality was unchanged.

Food for folivores: nutritional explanations linking diets to population density.

Ecologists want to explain why populations of animals are not evenly distributed across landscapes and often turn to nutritional explanations. In seeking to link population attributes with food quality, they often contrast nutritionally positive traits, such as the concentration of nitrogen, against negative ones, such as fibre concentration, by using a ratio of these traits. This specific ratio has attracted attention because it sometimes correlates with the biomass of colobine primates across sites in Asia and Africa. Although empirically successful, we have identified problems with the ratio that may explain why it fails under some conditions to predict colobine biomass. First, available nitrogen, rather than total nitrogen, is nutritionally important, while the presence of tannins is the major factor reducing the availability of nitrogen in browse plant species. Second, tannin complexes inflate measures of fibre. Finally, simple ratios may be unsound statistically because they implicitly assume isometric relationships between variables. We used data on the chemical composition of plants from three continents to examine the relationships between the concentrations of nitrogen, available nitrogen, fibre and tannins in foliage and to evaluate the nitrogen to fibre ratio. Our results suggest that the ratio of the concentration of nitrogen to fibre in leaves does sometimes closely correlate with the concentration of available nitrogen. However, the ratio may give misleading results when leaves contain high concentrations of tannins. The concentration of available nitrogen, which incorporates measures of total nitrogen, dry matter digestibility and tannins, should give a better indication of the nutritional value of leaves for herbivorous mammals that can readily be extrapolated to habitats.

The Art and Science of Mentorship in Cardiothoracic Surgery: A Systematic Review of the Literature.

BACKGROUND: As academic cardiothoracic surgeons focus on producing a new generation of successful surgeon leaders, mentorship has emerged as one of the most important variables influencing professional and personal success and satisfaction. This review explores the literature to determine the benefits, qualities, and features of the mentor relationship. METHODS: A comprehensive review was performed in February 2020 of Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and the SCOPUS Database using "'mentor"' as a primary search term. The titles and abstracts of these publications were then reviewed by 2 of the authors to identify relevant sources addressing topics related to mentorship in cardiothoracic surgery and also to identify 4 specific areas of focus: (1) the value of mentorship, (2) the skills needed to be an effective mentor, (3) effective approaches for identifying and receiving mentorship, and (4) the unique considerations associated with mentorship for traditionally underrepresented populations in surgery. RESULTS: Of 16,469 articles reviewed, 167 relevant manuscripts were identified, and 62 were included. CONCLUSIONS: There is undeniable value in mentorship when navigating a career in cardiothoracic surgery. By sharing the most significant features and skills of both ideal mentors and mentees, this review hoped to provide a framework to improve the quality of mentorship from both sides.

Limitations on Development of Polychlorinated Biphenyl Tissue Concentration Thresholds for Survival, Growth, and Reproduction in Fish.

Polychlorinated biphenyl exposure-response relationships for ecologically relevant endpoints in fish vary greatly whether based on lowest-effect thresholds (Berninger and Tillitt 2019) or all-response data (sensitivity analyses), which precludes use of a single fitted model per endpoint to predict risk or injury to mixed fish populations. PCB = polychlorinated biphenyl.

Application of the Target Lipid Model to Assess Toxicity of Heterocyclic Aromatic Compounds to Aquatic Organisms.

Heterocyclic aromatic compounds can be found in crude oil and coal and often co-exist in environmental samples with their homocyclic aromatic counterparts. The target lipid model (TLM) is a modeling framework that relates aquatic toxicity to the octanol-water partition coefficient (KOW ) that has been calibrated and validated for hydrocarbons. A systematic analysis of the applicability of the TLM to heterocyclic aromatic compounds has not been performed. The objective of the present study was to compile reliable toxicity data for heterocycles and determine whether observed toxicity could be successfully described by the TLM. Results indicated that the TLM could be applied to this compound class by adopting an empirically derived coefficient that accounts for partitioning between water and lipid. This coefficient was larger than previously reported for aromatic hydrocarbons, indicating that these heterocyclic compounds exhibit higher affinity to target lipid and toxicity. A mechanistic evaluation confirmed that the hydrogen bonding accepting moieties of the heteroatoms helped explain differences in partitioning behavior. Given the TLM chemical class coefficient reported in the present study, heterocyclic aromatics can now be explicitly incorporated in TLM-based risk assessments of petroleum substances, other products, or environmental media containing these compounds. Environ Toxicol Chem 2021;40:3000-3009. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Symptom exaggeration in post-secondary students: preliminary base rates in a Canadian sample.

Recent studies conducted at American post-secondary institutions report that a high proportion of college students seeking evaluations for either attention-deficit/hyperactivity disorder or learning disorders fail symptom validity tests (SVTs), calling into question the validity of their performance on standardized assessment measures. The current study undertook to investigate the rate of SVT failure in a Canadian post-secondary sample, drawing on assessment data from a large regional assessment facility. Evaluating the data from 144 consecutively tested students, the present study found that 14.6% of students failed an SVT, and those who failed returned lower scores on many other assessment measures compared with those who passed. These findings indicate that the rate of symptom exaggeration or low test-taking effort may be lower in Canadian samples than in U.S. samples but still represents a substantial number of students. Recommendations and suggestions for future directions are discussed.

A data-driven framework for defining stages of oil weathering.

Oil weathering is often described subjectively after a spill. Adjectives like "moderate" and "severe" help define the extent of oil loss but fail to communicate quantitatively and reproducibly the degree of weathering. The use of subjective weathering terms often leads to misperceptions about persistence and toxicity of oil residues in the environment. The weathering of MC252 oil from the Deepwater Horizon spill started immediately after release during the 1500-m ascent to the sea surface and continued as it was transported on the surface and reached the shoreline. Weathering processes included evaporation, dissolution, photo-degradation, and biodegradation, among others. With extensive sample collection and detailed chemistry and source fingerprinting analyses, the Deepwater Horizon data provide a unique opportunity to evaluate weathering processes semi-quantitatively. An objective method of defining the degree of oil weathering is developed based on the detailed chemical results for over 700 MC252 oil samples from the environment.

The National Emphysema Treatment Trial: summary and update.

Surgery for severe emphysema involves a cohort of patients who are already at risk for increased perioperative morbidity and mortality. Through the careful screening and selection process, improved intraoperative techniques and rigorous attention to postoperative care, the NETT managed to yield acceptable improvements in survival and functional outcomes in this fragile patient cohort and these benefits were sustained over the long-term. Identification of the characteristics associated with a higher risk of death has provided tangible patient selection criteria for the ongoing application of LVRS. Because the NETT was such a large-scale study, the protocols that were developed had to be standardized across several centers. This produced reliable and reproducible standards for evaluation and treatment that can be applied to the surgical treatment of emphysema. When considering these criteria, although individualized patient selection is important, only patients with upper-lobe predominant disease on chest CT and possibly those with non-upper-lobe predominant disease who also have low baseline exercise capacity are appropriate candidates for LVRS. Expectedly, questions remain regarding the exact mechanism whereby the benefits derived from LVRS are obtained. Additionally, the benefit of LVRS in patients with heterogeneous but non-upper-lobe predominant disease remains to be further elucidated. In spite of the limitations of the study, the NETT, through a tremendous coordinated effort, provided valuable outcomes data, answered the pressing questions regarding lung volume reduc-tion surgery that existed at the time, and provided valuable insight into other facets of emphysema physiology and management through direct observation. Based on the NETT findings, in November 2003, CMS published criteria for expanded coverage for LVRS to include non-high-risk patients who demonstrated either upper-lobe predominant emphysema, or non-upper-lobe predominant emphysema and low baseline exercise capacity and who met the screening guidelines.29 This study not only provided data regarding the clinical efficacy of LRVS, but it was instrumental in determining health policy guidelines for the surgical management of emphysema.