Phosphorus-mediated sp2-sp3 couplings for C-H fluoroalkylation of azines.

Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile1-4. Drug candidates increasingly contain trifluoromethyl (CF3) and difluoromethyl (CF2H) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life5,6. New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CF2X groups (where X is F or H) in complex drug-like molecules are rare7-13. Pyridines are the most common aromatic heterocycles in pharmaceuticals14, but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development15-17. Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp2-sp3 coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.

Harnessing the power of artificial intelligence to advance cell therapy.

Cell therapies are powerful technologies in which human cells are reprogrammed for therapeutic applications such as killing cancer cells or replacing defective cells. The technologies underlying cell therapies are increasing in effectiveness and complexity, making rational engineering of cell therapies more difficult. Creating the next generation of cell therapies will require improved experimental approaches and predictive models. Artificial intelligence (AI) and machine learning (ML) methods have revolutionized several fields in biology including genome annotation, protein structure prediction, and enzyme design. In this review, we discuss the potential of combining experimental library screens and AI to build predictive models for the development of modular cell therapy technologies. Advances in DNA synthesis and high-throughput screening techniques enable the construction and screening of libraries of modular cell therapy constructs. AI and ML models trained on this screening data can accelerate the development of cell therapies by generating predictive models, design rules, and improved designs.

Space weather disrupts nocturnal bird migration.

Space weather, including solar storms, can impact Earth by disturbing the geomagnetic field. Despite the known dependence of birds and other animals on geomagnetic cues for successful seasonal migrations, the potential effects of space weather on organisms that use Earth's magnetic field for navigation have received little study. We tested whether space weather geomagnetic disturbances are associated with disruptions to bird migration at a macroecological scale. We leveraged long-term radar data to characterize the nightly migration dynamics of the nocturnally migrating North American avifauna over 22 y. We then used concurrent magnetometer data to develop a local magnetic disturbance index associated with each radar station (ΔBmax), facilitating spatiotemporally explicit analyses of the relationship between migration and geomagnetic disturbance. After controlling for effects of atmospheric weather and spatiotemporal patterns, we found a 9 to 17% decrease in migration intensity in both spring and fall during severe space weather events. During fall migration, we also found evidence for decreases in effort flying against the wind, which may represent a depression of active navigation such that birds drift more with the wind during geomagnetic disturbances. Effort flying against the wind in the fall was most reduced under both overcast conditions and high geomagnetic disturbance, suggesting that a combination of obscured celestial cues and magnetic disturbance may disrupt navigation. Collectively, our results provide evidence for community-wide avifaunal responses to geomagnetic disturbances driven by space weather during nocturnal migration.

Dissecting the difference in tree species richness between Africa and South America.

SignificanceOur full-scale comparison of Africa and South America's lowland tropical tree floras shows that both Africa and South America's moist and dry tree floras are organized similarly: plant families that are rich in tree species on one continent are also rich in tree species on the other continent, and these patterns hold across moist and dry environments. Moreover, we confirm that there is an important difference in tree species richness between the two continents, which is linked to a few families that are exceptionally diverse in South American moist forests, although dry formations also contribute to this difference. Plant families only present on one of the two continents do not contribute substantially to differences in tree species richness.

Stroke-associated intergenic variants modulate a human FOXF2 transcriptional enhancer.

SNPs associated with human stroke risk have been identified in the intergenic region between Forkhead family transcription factors FOXF2 and FOXQ1, but we lack a mechanism for the association. FoxF2 is expressed in vascular mural pericytes and is important for maintaining pericyte number and stabilizing small vessels in zebrafish. The stroke-associated SNPs are located in a previously unknown transcriptional enhancer for FOXF2, functional in human cells and zebrafish. We identify critical enhancer regions for FOXF2 gene expression, including binding sites occupied by transcription factors ETS1, RBPJ, and CTCF. rs74564934, a stroke-associated SNP adjacent to the ETS1 binding site, decreases enhancer function, as does mutation of RPBJ sites. rs74564934 is significantly associated with the increased risk of any stroke, ischemic stroke, small vessel stroke, and elevated white matter hyperintensity burden in humans. Foxf2 has a conserved function cross-species and is expressed in vascular mural pericytes of the vessel wall. Thus, stroke-associated SNPs modulate enhancer activity and expression of a regulator of vascular stabilization, FOXF2, thereby modulating stroke risk.

Opportunities for fundamental physics research with radioactive molecules.

Molecules containing short-lived, radioactive nuclei are uniquely positioned to enable a wide range of scientific discoveries in the areas of fundamental symmetries, astrophysics, nuclear structure, and chemistry. Recent advances in the ability to create, cool, and control complex molecules down to the quantum level, along with recent and upcoming advances in radioactive species production at several facilities around the world, create a compelling opportunity to coordinate and combine these efforts to bring precision measurement and control to molecules containing extreme nuclei. In this manuscript, we review the scientific case for studying radioactive molecules, discuss recent atomic, molecular, nuclear, astrophysical, and chemical advances which provide the foundation for their study, describe the facilities where these species are and will be produced, and provide an outlook for the future of this nascent field.

Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.

Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of CFTR in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR was compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR was quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared to control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for CFTR was accompanied by decreases in mRNA for the Cl-/HCO3- exchanger SLC26A3, K+ channels (KCNQ1, KCNN4), and vasoactive intestinal polypeptide receptor (VIPR1) which suggest a driving force for change in secretory function of gallbladder epithelial cells in the pathogenesis of mucocele formation. There were no significant differences in CFTR gene variant frequency, type, or predicted impact comparing low risk, high risk, and definitively diagnosed groups of dogs. This study describes a unique, naturally occurring muco-obstructive disease of the canine gallbladder, with uncanny similarity to cystic fibrosis, and driven by underlying failure of CFTR function.

Defining the value of medical microbiology consultation.

Medical microbiologists, defined as doctoral-level laboratory directors with subspecialty training in medical microbiology, lead the clinical laboratory operations through activities such as clinical consultations, oversight of diagnostic testing menu, institutional leadership, education, and scholastic activities. However, unlike their clinical colleagues, medical microbiologists are largely unable to bill for clinical consultations performed within the hospital and, therefore, unable to generate relative value units or a similar quantifiable metric. As hospital budgets tighten and justification of staffing becomes a necessity, this may present a challenge to the medical microbiologist attempting to prove their value to the organization. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. Consults were generated equally from internal (laboratory-based) and external (hospital-based) parties, with the majority directly impacting patient management. Near universal acceptance of the medical microbiologist's recommendation highlights the worth derived from their expertise. External consults required more time commitment from the medical microbiologist than internal consults, although both presented ample opportunity for secondary value, including impact through stewardship, education, clinical guidance, and cost reduction. This study is a description of the content and impact of consultations that underscore the importance of the medical microbiologist as a key member of the healthcare team. IMPORTANCE: Medical microbiologists are invaluable to the clinical microbiology laboratory and the healthcare system as a whole. However, as medical microbiologists do not regularly generate relative value units, capturing and quantifying the value provided is challenging. As hospital budgets tighten, justification of staffing becomes a necessity. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. To our knowledge, this is the first study to provide detailed evaluation of the consultative value provided by medical microbiologists.

Heritable differences in abundance of bacterial rhizosphere taxa are correlated with fungal necrotrophic pathogen resistance.

Host-microbe interactions are increasingly recognized as important drivers of organismal health, growth, longevity and community-scale ecological processes. However, less is known about how genetic variation affects hosts' associated microbiomes and downstream phenotypes. We demonstrate that sunflower (Helianthus annuus) harbours substantial, heritable variation in microbial communities under field conditions. We show that microbial communities co-vary with heritable variation in resistance to root infection caused by the necrotrophic pathogen Sclerotinia sclerotiorum and that plants grown in autoclaved soil showed almost complete elimination of pathogen resistance. Association mapping suggests at least 59 genetic locations with effects on both microbial relative abundance and Sclerotinia resistance. Although the genetic architecture appears quantitative, we have elucidated previously unexplained genetic variation for resistance to this pathogen. We identify new targets for plant breeding and demonstrate the potential for heritable microbial associations to play important roles in defence in natural and human-altered environments.

Rectal Cancer Survival for Residual Carcinoma In Situ Versus Pathologic Complete Response After Neoadjuvant Therapy.

BACKGROUND: Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE: To compare the survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN: Retrospective cohort study. SETTING: National public database. PATIENTS: A total of 4594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative ypTis or ypT0 on final pathology were included. Of these, 4321 patients (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURE: Overall survival. RESULTS: The median age was 60 years, and 1822 patients (39.7%) were women. On initial staging, 54.5% (n = 2503) had stage II disease and 45.5% (n = 2091) had stage III disease. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42; 95% CI, 1.04-1.95; p = 0.028). Other factors associated with decreased overall survival were older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage II and stage III. LIMITATIONS: Standard therapy versus total neoadjuvant therapy could not be abstracted. Overall survival was defined as the time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS: ypTis is associated with worse overall survival than ypT0 for patients with locally advanced rectal cancer who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract . SUPERVIVENCIA DEL CNCER DE RECTO PARA EL CARCINOMA RESIDUAL IN SITU VS RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE: ANTECEDENTESLa respuesta patológica completa después de la quimiorradioterapia neoadyuvante para el cáncer de recto se asocia con una mayor supervivencia. No está claro si el carcinoma residual in situ presagia un resultado similar.OBJETIVOComparar la supervivencia de pacientes con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante y lograron un carcinoma patológico in situ versus una respuesta patológica completa.DISEÑOEstudio de cohorte retrospectivo.ESCENARIOBase de datos pública nacional.PACIENTESSe incluyeron 4,594 pacientes de la Base de Datos Nacional de Cáncer de 2006 a 2016 con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante, fueron sometidos a cirugía y tuvieron ganglios negativos, ypTis o ypT0 en el reporte patológico final. 4.321 (94,1%) tuvieron ypT0 y 273 (5,9%) tuvieron ypTis en el reporte final.PRINCIPALES MEDIDAS DE RESULTADOSupervivencia general.RESULTADOSLa mediana de edad fue de 60 años. 1.822 pacientes (39,7%) fueron mujeres. El 54,5% (n = 2.503) tuvo la enfermedad en estadio II y el 45,5% (n = 2.091) tuvo la enfermedad en estadio III según la estadificación inicial. El grupo ypTis tuvo una supervivencia general reducida en comparación con el grupo ypT0 (HR 1,42, IC 95 % 1,04-1,95, p = 0,028). Otros factores asociados con una menor supervivencia general fueron una edad más avanzada al momento del diagnóstico, un aumento de la puntuación de Charlson-Deyo y un grado tumoral poco diferenciado. Las variables asociadas con una mejor supervivencia fueron el sexo femenino, el seguro privado y la recepción de quimioterapia neoadyuvante y adyuvante. Para la cohorte total, no hubo diferencias en la supervivencia entre el estadio clínico 2 y el estadio 3.LIMITACIONESNo se pudo resumir el tratamiento estándar versus el tratamiento neoadyuvante total. La supervivencia general se definió como el tiempo transcurrido desde la cirugía hasta la muerte por cualquier causa o último contacto, lo que permite algunas muertes erróneamente clasificadas.CONCLUSIONESypTis se asocia con una peor supervivencia general que ypT0 en pacientes con cáncer de recto localmente avanzado que reciben quimiorradioterapia neoadyuvante seguida de cirugía. Para esta cohorte, el estadio clínico no fue un predictor significativo de supervivencia. Se necesitan ensayos prospectivos que comparen la supervivencia de estos resultados patológicos. ( Traducción-Dr Osvaldo Gauto ).

Cadaveric Study of Colon-Lengthening Maneuvers After Sigmoidectomy.

BACKGROUND: Creation of a tension-free colorectal anastomosis after left colon resection or low anterior resection is a key requirement for technical success. The relative contribution of each of a series of known lengthening maneuvers remains incompletely characterized. OBJECTIVE: The aim of this study was to compare technical procedures for lengthening of the left colon before rectal anastomosis. DESIGN: A series of lengthening maneuvers was performed on 15 fresh cadavers. Mean distance gained was measured for each successive maneuver, including 1) high inferior mesenteric artery ligation, 2) splenic flexure takedown, and 3) high inferior mesenteric vein ligation by the ligament of Treitz. SETTING: Cadaveric study. MAIN OUTCOME MEASURES: The premobilization and postmobilization position of the proximal colonic end was measured relative to the inferior edge of the sacral promontory. Measurements of the colonic length relative to the sacral promontory were taken after each mobilization maneuver. The inferior mesenteric artery, sigmoid colon, and rectum specimen lengths were measured. The distance from the inferior border of the sacral promontory to the pelvic floor was measured along the sacral curvature. RESULTS: Mean sigmoid colon resection length was 34.7 ± 11.1 cm. Before any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained. LIMITATIONS: The study was limited by nature of being a cadaver study. CONCLUSIONS: Stepwise lengthening maneuvers allow significant additional reach to allow a tension-free left colon to rectal anastomosis. See Video Abstract . ESTUDIO CADAVRICO DE MANIOBRAS DE ALARGAMIENTO COLNICO TRAS UNA SIGMOIDECTOMA: ANTECEDENTES:La creación de una anastomosis colorrectal libre de tensión tras una resección de colon izquierdo o tras una resección anterior baja es un requisito clave para el éxito relacionado con la técnica quirúrgica. La relativa contribución de las diversas maniobras de alargamiento permanece caracterizada de manera incompleta.OBJETIVO:El propósito de este estudio fue la de comparar procedimientos técnicos de alargamiento del colon izquierdo previo a la anastomosis rectal.DISEÑO:Una serie de maniobras de alargamiento fueron realizados en 15 cadáveres frescos. La distancia promedio ganada fue medida para cada maniobra sucesiva, incluyendo (1) ligadura alta de la arteria mesentérica inferior, (2) descenso del ángulo esplénico, (3) ligadura alta de la vena mesentérica interior mediante el ligamento de Treitz.AJUSTES:Estudio cadavérico.PRINCIPALES MEDIDAS DE RESULTADO:La posición premobilizacion y postmobilizacion del extremo proximal del colon fue medido tomando en cuenta el borde inferior del promontorio sacro. Las mediciones de la longitud colónica en relación al sacro fueron tomadas luego de cada maniobra de movilización. Fueron tomadas así mismo las longitudes de la arteria mesentérica inferior, el colon sigmoides y recto. Las distancias desde el borde inferior del promontorio sacro al suelo pelvico fueron medidas a lo largo de la curvatura sacra.RESULTADOS:Average sigmoid colon resection length was 34.7 ± 11.1 cm. Prior to any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained.LIMITACIONES:Este estudio tuvo como limitación la naturaleza de haber sido un estudio cadavérico.CONCLUSIONES:Maniobras de alargamiento permiten un alcance adicional significativo permitiendo de esta manera una anastomosis de colon izquierdo a recto libre de anastomosis. (Traducción-Dr Osvaldo Gauto ).

Chasing and surfing seasonal waves: Avian migration through the US tracks land surface phenology in fall, but not spring.

Climate change is altering the timing of seasonal events for many taxa. There is limited understanding of how northward/southward songbird migration follows or is limited by the latitudinal progression of seasonal transitions. Consistent environmental conditions that migrating birds encounter across latitudes likely represent or correlate with important resources or limiting factors for migration. We tested whether migratory passage-observed via radar-consistently tracked land surface variables and phenophases across latitudes in the US Central Flyway in both spring and fall. The daily temperatures, precipitation and vegetation greenness occurring on 10%, 50% and 90% cumulative passage dates changed substantially with latitude, indicating that most migrants experienced rapidly changing conditions as they headed north or south. Temperature did not limit the progression of migration in either season. Peak spring migration in the southern US occurred nearly 40 days after the spring green wave, the northward progression of vegetation growth, but nearly caught up to green-up at 48° N. Spring migration phenology may have evolved to prioritize earlier arrival for breeding. Across all latitudes, peak fall migration coincided with the same land surface phenophase, an interval of 26 days prior to dormancy onset. Migrants may rely on phenological events in vegetation during fall stopovers. Considering that (a) migratory passage tracked fall land surface phenology across latitudes at a continental scale, (b) previous studies at local scales have demonstrated the importance of fruit during fall migratory stopover and (c) fruiting phenology in North America is occurring later over time while fall migration is advancing, the potential for mismatch between fall fruiting and bird migration phenology urgently needs further investigation.

Signet ring cells and conditional survival after trimodality therapy for esophageal adenocarcinoma.

BACKGROUND AND METHODS: Although signet ring cell (SRC) histology is associated with resistance to neoadjuvant chemoradiotherapy and worse overall survival (OS) in esophageal adenocarcinoma (EAC), its prognostic relationship among patients who survive the early period following resection is unknown. EAC patients who underwent trimodality therapy at a single institution (2006-2018) were identified. Bayesian multivariable regression (BMR) analyses of OS and additional OS from a 3-year landmark were performed. RESULTS: Of 631 patients, SRCs were present in 16.0% (N = 101). SRC was associated with shorter median OS (45.8 [95% confidence interval: 31.0-96.7] vs. 79.8 [63.0-107.2] months; p = 0.014). In BMR analysis, the absence of an SRC component was moderately associated with improved OS (probability of beneficial effect, PBE = 0.879). Three-year conditional BMR analysis of additional OS (N = 357) showed that SRC status no longer had a prognostic effect (PBE = 0.546); higher pathological stage was strongly associated with worse additional OS (PBE < 0.001). CONCLUSIONS: The presence of SRC portends worse OS following trimodality therapy for EAC. However, this prognostic impact is dynamic and abates by 3 years postoperatively. In contrast, a higher pathological stage is strongly associated with poor overall and 3-year conditional survival. DISCUSSION: These findings may inform postoperative patient counseling and surveillance protocols.

T cells selectively filter oscillatory signals on the minutes timescale.

T cells experience complex temporal patterns of stimulus via receptor-ligand-binding interactions with surrounding cells. From these temporal patterns, T cells are able to pick out antigenic signals while establishing self-tolerance. Although features such as duration of antigen binding have been examined, our understanding of how T cells interpret signals with different frequencies or temporal stimulation patterns is relatively unexplored. We engineered T cells to respond to light as a stimulus by building an optogenetically controlled chimeric antigen receptor (optoCAR). We discovered that T cells respond to minute-scale oscillations of activation signal by stimulating optoCAR T cells with tunable pulse trains of light. Systematically scanning signal oscillation period from 1 to 150 min revealed that expression of CD69, a T cell activation marker, reached a local minimum at a period of ∼25 min (corresponding to 5 to 15 min pulse widths). A combination of inhibitors and genetic knockouts suggest that this frequency filtering mechanism lies downstream of the Erk signaling branch of the T cell response network and may involve a negative feedback loop that diminishes Erk activity. The timescale of CD69 filtering corresponds with the duration of T cell encounters with self-peptide-presenting APCs observed via intravital imaging in mice, indicating a potential functional role for temporal filtering in vivo. This study illustrates that the T cell signaling machinery is tuned to temporally filter and interpret time-variant input signals in discriminatory ways.

Drivers of fatal bird collisions in an urban center.

Millions of nocturnally migrating birds die each year from collisions with built structures, especially brightly illuminated buildings and communication towers. Reducing this source of mortality requires knowledge of important behavioral, meteorological, and anthropogenic factors, yet we lack an understanding of the interacting roles of migration, artificial lighting, and weather conditions in causing fatal bird collisions. Using two decades of collision surveys and concurrent weather and migration measures, we model numbers of collisions occurring at a large urban building in Chicago. We find that the magnitude of nocturnal bird migration, building light output, and wind conditions are the most important predictors of fatal collisions. The greatest mortality occurred when the building was brightly lit during large nocturnal migration events and when winds concentrated birds along the Chicago lakeshore. We estimate that halving lighted window area decreases collision counts by 11× in spring and 6× in fall. Bird mortality could be reduced by ∼60% at this site by decreasing lighted window area to minimum levels historically recorded. Our study provides strong support for a relationship between nocturnal migration magnitude and urban bird mortality, mediated by light pollution and local atmospheric conditions. Although our research focuses on a single site, our findings have global implications for reducing or eliminating a critically important cause of bird mortality.

Individual and Age Differences in Item and Context Memory.

We investigated whether individuals who are good at recognizing previously presented items are also good at recognizing the context in which items were presented. We focused specifically on whether the relation between item recognition and context recognition abilities differs in younger and older adults. It has been hypothesized that context memory declines more rapidly in older adults due to an age-related deficit in associative binding or recollection. To test this hypothesis, younger and older adults were asked to remember lists of names and objects, as well as the context (i.e. their size, location, and color) that accompanied those items. Following presentation of each list, recognition tests for items and context were administered. Confirmatory factor analysis (CFA) models analyzing both item and context scores together provided no evidence of separate factors for item and context memory. Instead, the best-fitting model separated performance by item-type, regardless of context, and no differences were found in the structure of these abilities in younger and older adults. These findings are consistent with the limited previous latent variable research on context memory in aging suggesting that there is no context recognition memory ability separable from item memory in younger nor older adults. Instead, individual differences in recognition memory abilities may be specific to the domain of the studied stimulus.

Evaluation of thoracic duct ligation and unilateral subphrenic pericardiectomy via a left fourth intercostal approach in normal canine cadavers.

OBJECTIVE: To investigate a left-sided fourth intercostal approach to thoracic duct (TD) ligation and unilateral subphrenic pericardiectomy in dogs. STUDY DESIGN: Retrospective computed tomography (CT) review and cadaveric study. ANIMALS: Thirteen dogs with idiopathic chylothorax and 10 canine cadavers. METHODS: A retrospective study of CT lymphangiograms in client-owned dogs with idiopathic chylothorax evaluated location and branching of the TD at the left fourth intercostal space. A cadaveric study evaluated the efficacy of TD ligation at this site. Following methylene blue mesenteric lymph node injection, TDs were identified through a left fourth intercostal thoracotomy, ligated, and sealed. Unilateral subphrenic pericardiectomy was performed through the same incision. Computed tomography scans were performed to determine the success of TD ligation. RESULTS: A review of lymphangiograms revealed a single TD in 10/13 clinical cases at the fourth intercostal space. Three cases had additional branches. Thoracic duct ligation via a left fourth intercostal thoracotomy was successful in nine out of 10 cadavers. A single branch was noted intraoperatively in six out of 10, and two branches were noted in four out of 10 cadavers. All branches were observed on the left side of the esophagus. CONCLUSION: TD ligation at the left fourth intercostal space was successfully performed in 9/10 canine cadavers and appeared feasible in a retrospective review of 10/13 clinical cases. Unilateral subphrenic pericardiectomy can also be performed via this approach. CLINICAL SIGNIFICANCE: Fewer thoracic duct branches at this location in comparison with the standard caudal location may simplify TD ligation. If elected, unilateral subphrenic pericardiectomy can be performed through the same incision. Further investigation in clinical patients is warranted.

Barriers to Implementation of Advanced Endoscopic Procedures.

Advanced endoscopy has been shown to be useful in the diagnosis and treatment of both benign and low-grade malignant colorectal lesions. In fact, advanced endoscopic procedures are being adopted as standard approaches to these lesions in many places around the world; however, their implementation in the United States has not been as widespread. We ascribe the difficulty in implementation to two reasons: (1) lack of advanced endoscopic training and (2) failure in reimbursement models as they relate to endoscopy. In this article, we hope to describe these barriers and inspire colorectal surgeons to try and overcome them. As surgical specialists with a mastery of endoscopic techniques, colorectal surgeons would be able to maximize benefit for their patients and minimize health care costs in the long run.

Range restricted old and young lineages show the southern Western Ghats to be both a museum and a cradle of diversity for woody plants.

The Western Ghats (WG) mountain chain is a global biodiversity hotspot with high diversity and endemicity of woody plants. The latitudinal breadth of the WG offers an opportunity to determine the evolutionary drivers of latitudinal diversity patterns. We examined the spatial patterns of evolutionary diversity using complementary phylogenetic diversity and endemism measures. To examine if different regions of the WG serve as a museum or cradle of evolutionary diversity, we examined the distribution of 470 species based on distribution modelling and occurrence locations across the entire region. In accordance with the expectation, we found that the southern WG is both a museum and cradle of woody plant evolutionary diversity, as a higher proportion of both old and young evolutionary lineages are restricted to the southern WG. The diversity gradient is likely driven by high geo-climatic stability in the south and phylogenetic niche conservatism for moist and aseasonal sites. This is corroborated by persistent lineage nestedness at almost all evolutionary depths (10-135 million years), and a strong correlation of evolutionary diversity with drought seasonality, precipitation and topographic heterogeneity. Our results highlight the global value of the WG, demonstrating, in particular, the importance of protecting the southern WG-an engine of plant diversification and persistence.

Diversity and divergence: evolution of secondary metabolism in the tropical tree genus Inga.

Plants are widely recognized as chemical factories, with each species producing dozens to hundreds of unique secondary metabolites. These compounds shape the interactions between plants and their natural enemies. We explore the evolutionary patterns and processes by which plants generate chemical diversity, from evolving novel compounds to unique chemical profiles. We characterized the chemical profile of one-third of the species of tropical rainforest trees in the genus Inga (c. 100, Fabaceae) using ultraperformance liquid chromatography-mass spectrometry-based metabolomics and applied phylogenetic comparative methods to understand the mode of chemical evolution. We show: each Inga species contain structurally unrelated compounds and high levels of phytochemical diversity; closely related species have divergent chemical profiles, with individual compounds, compound classes, and chemical profiles showing little-to-no phylogenetic signal; at the evolutionary time scale, a species' chemical profile shows a signature of divergent adaptation. At the ecological time scale, sympatric species were the most divergent, implying it is also advantageous to maintain a unique chemical profile from community members; finally, we integrate these patterns with a model for how chemical diversity evolves. Taken together, these results show that phytochemical diversity and divergence are fundamental to the ecology and evolution of plants.