A super-massive Neptune-sized planet.

Neptune-sized planets exhibit a wide range of compositions and densities, depending on factors related to their formation and evolution history, such as the distance from their host stars and atmospheric escape processes. They can vary from relatively low-density planets with thick hydrogen-helium atmospheres1,2 to higher-density planets with a substantial amount of water or a rocky interior with a thinner atmosphere, such as HD 95338 b (ref. 3), TOI-849 b (ref. 4) and TOI-2196 b (ref. 5). The discovery of exoplanets in the hot-Neptune desert6, a region close to the host stars with a deficit of Neptune-sized planets, provides insights into the formation and evolution of planetary systems, including the existence of this region itself. Here we show observations of the transiting planet TOI-1853 b, which has a radius of 3.46 ± 0.08 Earth radii and orbits a dwarf star every 1.24 days. This planet has a mass of 73.2 ± 2.7 Earth masses, almost twice that of any other Neptune-sized planet known so far, and a density of 9.7 ± 0.8 grams per cubic centimetre. These values place TOI-1853 b in the middle of the Neptunian desert and imply that heavy elements dominate its mass. The properties of TOI-1853 b present a puzzle for conventional theories of planetary formation and evolution, and could be the result of several proto-planet collisions or the final state of an initially high-eccentricity planet that migrated closer to its parent star.

Omission of axillary lymph node dissection for breast cancer patients with three or more positive sentinel lymph nodes.

PURPOSE: The ACOSOG Z0011 (Z11) trial assessed the benefit of axillary dissection (ALND) for breast cancer patients with sentinel lymph node (SLN) metastases; however, Z11 excluded patients with ≥ 3 positive SLNs. We analyzed trends in ALND omission in patients with ≥ 3 positive SLNs. METHODS: Women with ≥ 3 positive SLNs who underwent breast-conserving surgery (BCS) or mastectomy between 2018 and 2020 in the National Cancer Database were included using SLN codes initiated in 2018. Patients with stage IV disease, recurrent breast cancer, and who underwent neoadjuvant chemotherapy were excluded. A multivariable logistic regression model was utilized to determine the proportion who received ALND and factors associated with ALND omission. A subgroup analysis was performed among patients who met the remainder of the Z11 inclusion criteria (BCS, T1/T2 breast cancer). RESULTS: We identified 3654 patients with ≥ 3 positive SLNs. ALND was omitted in 37% of patients, and omission significantly increased from 2018 to 2020 (29% vs. 41%, p < 0.0001). Older age, lower grade tumors, no radiation, non-academic facility, BCS, more SLNs examined and fewer positive SLNs were significantly associated with ALND omission. 942 patients with ≥ 3 positive SLNs met the remainder of the Z11 inclusion criteria. ALND was omitted in 49% of these patients, and omission increased from 2018 to 2020 (44% vs. 49%, p = 0.22). CONCLUSION: Approximately one-third of patients with ≥ 3 positive SLNs do not undergo ALND; omission of ALND increased from 2018 to 2020. Studies assessing oncologic outcomes of patients with ≥ 3 positive SLNs who do and do not receive ALND are required.

A time-series analysis of blood-based biomarkers within a 25-year longitudinal dolphin cohort.

Causal interactions and correlations between clinically-relevant biomarkers are important to understand, both for informing potential medical interventions as well as predicting the likely health trajectory of any individual as they age. These interactions and correlations can be hard to establish in humans, due to the difficulties of routine sampling and controlling for individual differences (e.g., diet, socio-economic status, medication). Because bottlenose dolphins are long-lived mammals that exhibit several age-related phenomena similar to humans, we analyzed data from a well controlled 25-year longitudinal cohort of 144 dolphins. The data from this study has been reported on earlier, and consists of 44 clinically relevant biomarkers. This time-series data exhibits three starkly different influences: (A) directed interactions between biomarkers, (B) sources of biological variation that can either correlate or decorrelate different biomarkers, and (C) random observation-noise which combines measurement error and very rapid fluctuations in the dolphin's biomarkers. Importantly, the sources of biological variation (type-B) are large in magnitude, often comparable to the observation errors (type-C) and larger than the effect of the directed interactions (type-A). Attempting to recover the type-A interactions without accounting for the type-B and type-C variation can result in an abundance of false-positives and false-negatives. Using a generalized regression which fits the longitudinal data with a linear model accounting for all three influences, we demonstrate that the dolphins exhibit many significant directed interactions (type-A), as well as strong correlated variation (type-B), between several pairs of biomarkers. Moreover, many of these interactions are associated with advanced age, suggesting that these interactions can be monitored and/or targeted to predict and potentially affect aging.

Evaluation of the safety and efficacy of fecal microbiota transplantations in bottlenose dolphins (Tursiops truncatus) using metagenomic sequencing.

AIMS: Gastrointestinal disease is a leading cause of morbidity in bottlenose dolphins (Tursiops truncatus) under managed care. Fecal microbiota transplantation (FMT) holds promise as a therapeutic tool to restore gut microbiota without antibiotic use. This prospective clinical study aimed to develop a screening protocol for FMT donors to ensure safety, determine an effective FMT administration protocol for managed dolphins, and evaluate the efficacy of FMTs in four recipient dolphins. METHODS AND RESULTS: Comprehensive health monitoring was performed on donor and recipient dolphins. Fecal samples were collected before, during, and after FMT therapy. Screening of donor and recipient fecal samples was accomplished by in-house and reference lab diagnostic tests. Shotgun metagenomics was used for sequencing. Following FMT treatment, all four recipient communities experienced engraftment of novel microbial species from donor communities. Engraftment coincided with resolution of clinical signs and a sustained increase in alpha diversity. CONCLUSION: The donor screening protocol proved to be safe in this study and no adverse effects were observed in four recipient dolphins. Treatment coincided with improvement in clinical signs.

Chemotherapy refusal and subsequent survival in healthy older women with high genomic risk estrogen receptor-positive breast cancer.

BACKGROUND: Patients with estrogen receptor (ER)-positive, HER2-negative breast cancer (BC), and high-risk 21-gene recurrence score (RS) results benefit from chemotherapy. We evaluated chemotherapy refusal and survival in healthy older women with high-RS, ER-positive BC. METHODS: Retrospective review of the National Cancer Database (2010-2017) identified women ≥ 65 years of age, with ER-positive, HER2-negative, high-RS (≥ 26) BC. Patients with Charlson Comorbidity Index ≥ 1, stage III/IV disease, or incomplete data were excluded. Women were compared by chemotherapy receipt or refusal using the Cochrane-Armitage test, multivariable logistical regression modeling, the Kaplan-Meier method, and Cox's proportional hazards modeling. RESULTS: 6827 women met study criteria: 5449 (80%) received chemotherapy and 1378 (20%) refused. Compared to women who received chemotherapy, women who refused were older (71 vs 69 years), were diagnosed more recently (2014-2017, 67% vs 61%), and received radiation less frequently (67% vs 71%) (p ≤ 0.05). Refusal was associated with decreased 5-year OS for women 65-74 (92% vs 95%) and 75-79 (85% vs 92%) (p ≤ 0.05), but not for women ≥ 80 years old (84% vs 91%; p = 0.07). On multivariable analysis, hazard of death increased with refusal overall (HR 1.12, 95% CI 1.04-1.2); but, when stratified by age, was not increased for women ≥ 80 years (HR 1.10, 95% CI 0.80-1.51). CONCLUSIONS: Among healthy women with high-RS, ER-positive BC, chemotherapy refusal was associated with decreased OS for women ages 65-79, but did not impact the OS of women ≥ 80 years old. Genomic testing may have limited utility in this population, warranting prudent shared decision-making and further study.

A giant planet undergoing extreme-ultraviolet irradiation by its hot massive-star host.

The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300-10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside, and is highly inflated-traits that have been linked to high insolation. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star.

A 25-y longitudinal dolphin cohort supports that long-lived individuals in same environment exhibit variation in aging rates.

While it is believed that humans age at different rates, a lack of robust longitudinal human studies using consensus biomarkers meant to capture aging rates has hindered an understanding of the degree to which individuals vary in their rates of aging. Because bottlenose dolphins are long-lived mammals that develop comorbidities of aging similar to humans, we analyzed data from a well-controlled, 25-y longitudinal cohort of 144 US Navy dolphins housed in the same oceanic environment. Our analysis focused on 44 clinically relevant hematologic and clinical chemistry measures recorded during routine blood draws throughout the dolphins' lifetimes. Using stepwise regression and general linear models that accommodate correlations between measures obtained on individual dolphins, we demonstrate that, in a manner similar to humans, dolphins exhibit independent and linear age-related declines in four of these measures: hemoglobin, alkaline phosphatase, platelets, and lymphocytes. Using linear regressions and analyses of covariance with post hoc Tukey-Kramer tests to compare slopes (i.e., linear age-related rates) of our four aging rate biomarkers among 34 individual dolphins aging from 10 y to up to 40 y old, we could identify slow and accelerated agers and differentiate subgroups that were more or less likely to develop anemia and lymphopenia. This study successfully documents aging rate differences over the lifetime of long-lived individuals in a controlled environment. Our study suggests that nonenvironmental factors influencing aging rate biomarkers, including declining hemoglobin and anemia, may be targeted to delay the effects of aging in a compelling model of human biology.

SUPERFICIAL CERVICAL LYMPHADENITIS ASSOCIATED WITH STREPTOCOCCUS PHOCAE IN FIVE COMMON BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS): A CASE SERIES.

Between 2009 and 2018, five common bottlenose dolphins (Tursiops truncatus) at the US Navy Marine Mammal Program presented with superficial cervical lymphadenitis. Clinical findings included ultrasonographic evidence of cervical lymph node enlargement, severe leukocytosis, elevated erythrocyte sedimentation rates, and reduced serum iron. Three of the dolphins presented with clinicopathologic changes without presence of clinical signs, and the other two cases additionally presented with partial to complete anorexia, lethargy, and refusal to participate in training sessions. Ultrasound-guided fine needle aspiration or biopsy of the affected lymph nodes yielded Streptococcus phocae by PCR in all cases, and the organism was cultured in one of five cases. Animals were treated with a combination of enteral, parenteral, intralesional antimicrobial, or a combination of those therapies and supportive care. Time to resolution of clinical disease ranged between 62 and 188 days. To the authors' knowledge, this is the first report of Streptococcus phocae cervical lymphadenitis in cetaceans. Streptococcus phocae lymphadenitis should be a differential for cervical lymphadenopathy in this species, especially when associated with pronounced systemic inflammation and a history of potential exposure.

Btg2 mutation induces renal injury and impairs blood pressure control in female rats.

Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well established that men and women develop BP impairment in different patterns and a recent emphasis has been placed on identifying mechanisms leading to the differences observed between the sexes in HTN development. The current work reported here builds on an extensive genetic mapping experiment that sought to identify genetic determinants of salt-sensitive (SS) HTN using the Dahl SS rat. BTG antiproliferation factor 2 (Btg2) was previously identified by our group as a candidate gene contributing to SS HTN in female rats. In the current study, Btg2 was mutated using transcription activator-like effector nuclease (TALEN)-targeted gene disruption on the SSBN congenic rat background. The Btg2 mutated rats exhibited impaired BP and proteinuria responses to a high-salt diet compared with wild-type rats. Differences in body weight, mutant pup viability, skeletal morphology, and adult nephron density suggest a potential role for Btg2 in developmental signaling pathways. Subsequent cell cycle gene expression assessment provides several additional signaling pathways that Btg2 may function through during salt handling in the kidney. The expression analysis also identified several potential upstream targets that can be explored to further isolate therapeutic approaches for SS HTN.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Prospective sampling bias in COVID-19 recruitment methods: experimental evidence from a national randomized survey testing recruitment materials.

BACKGROUND: In the context of the COVID-19 pandemic, social science research has required recruiting many prospective participants. Many researchers have explicitly taken advantage of widespread public interest in COVID-19 to advertise their studies. Leveraging this interest, however, risks creating unrepresentative samples due to differential interest in the topic. In this study, we investigate the design of survey recruitment materials with respect to the views of resultant participants. METHODS: Within a pan-Canadian survey (stratified random mail sampling, n = 1969), the design of recruitment invitations to prospective respondents was experimentally varied, with some prospective respondents receiving COVID-specific recruitment messages and others receiving more general recruitment messages (described as research about health and health policy). All respondents participated, however, in the same survey, allowing comparison of both demographic and attitudinal features between these groups. RESULTS: Respondents recruited via COVID-19 specific postcards were more likely to agree that COVID-19 is serious and believe that they were likely to contract COVID-19 compared to non-COVID respondents (odds = 0.71, p = 0.04; odds = 0.74, p = 0.03 respectively; comparing health to COVID-19 framed respondents). COVID-19 specific respondents were more likely to disagree that the COVID-19 threat was exaggerated compared to the non-COVID survey respondents (odds = 1.44, p = 0.02). CONCLUSIONS: COVID-19 recruitment framing garnered a higher response rate, as well as a sample with greater concern about coronavirus risks and impacts than respondents who received more neutrally framed recruitment materials.

Dietary effects on urinary physicochemistry in Navy bottlenose dolphins (Tursiops truncatus) for the prevention of ammonium urate kidney stones.

Bottlenose dolphins are susceptible to developing ammonium urate (NH4U) kidney stones. The current study was designed to test the hypothesis that diet influences the urinary physicochemistry risk factors associated with nephrolithiasis in dolphins. A comprehensive nutrient analysis was performed revealing that the baseline diet (BD) commonly fed to dolphins under professional care had a greater purine content and a more negative dietary cation-anion difference (DCAD) when compared with a model diet consumed by free-ranging dolphins. A modified diet (MD) was formulated to include free-ranging diet fish species and achieve a more positive DCAD. The BD had a more negative DCAD (-52 mEq/Mcal metabolizable energy) when compared with the MD (+51 mEq/Mcal ME), which more closely approximated the DCAD of the free-ranging model diet (+152 mEq/Mcal ME). Six dolphins (with stones) were fed the BD followed by the MD for a minimum of 4 wk. At the end of each feeding trial, a 6-h continuous urine collection was performed to compare urine parameters of dolphins fed the BD versus MD. Dolphins consuming the MD demonstrated a significant decrease in urinary ammonium, net acid excretion, saturation index of ammonium urate, and phosphorous, and a significant increase in urinary citrate and net gastrointestinal (GI) alkali absorption, as compared with urine parameters assessed when fed the BD. Increasing the proportion of free-ranging diet fish species and optimizing the DCAD positively influenced some of the risk factors believed to be associated with NH4U kidney stone development in bottlenose dolphins under professional care.

Role of biliary stent and neoadjuvant chemotherapy in the pancreatic tumor microbiome.

BACKGROUND: Intra-tumor microbiota have been implicated in pancreatic ductal adenocarcinoma (PDAC) development, treatment response and post-treatment survivorship. Moreover, therapeutic interventions targeting microbiota may improve the response to chemotherapy and immunotherapy, further emphasizing the critical need to understand the origins of and growth of bacteria within the pancreatic tumor microenvironment. Here, we studied the role of several clinical factors on the bacterial colonization of PDAC. RESULTS: We obtained matched tumor and normal pancreatic tissue specimens from 27 patients who had undergone surgical resection for PDAC between 2011 and 2015 from the University of Minnesota Biological Materials Procurement Network (BioNet). We found that 26 (48%) out of 54 pancreatic tissue samples harbored detectable bacterial communities using real-time PCR targeting the 16S rRNA gene. Bacterial colonization was detected significantly more frequently in samples from patients who had pancreatic head tumors, underwent Whipple procedure, or had preoperative biliary stent placement. There was also a significantly greater relative abundance of microbiota from the family Enterobacteriaceae among samples from patients who underwent biliary stent placement or neoadjuvant treatment with a combination of Gemcitabine and Paclitaxel. CONCLUSIONS: These findings suggest that biliary stent placement and neoadjuvant chemotherapy are associated with specific alterations that promote the infiltration and growth of intra-tumor bacteria in the setting of PDAC. Further studies exploring whether specific bacterial communities could contribute to increased chemoresistance will be essential for optimizing medical therapies in the future.

Surgeon decision-making for management of positive sentinel lymph nodes in the post-Multicenter Selective Lymphadenectomy Trial II era: A survey study.

BACKGROUND AND OBJECTIVES: Completion lymph node dissection (CLND) did not improve melanoma-specific survival for patients with sentinel lymph node (SLN)-positive melanoma in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II). We assessed surgeons' awareness of MSLT-II and its impact on CLND recommendations. METHODS: An anonymous online cross-sectional survey of the Society of Surgical Oncology membership evaluated surgeon thresholds in offering CLND using patient scenarios and clinicopathologic characteristics ranking. RESULTS: Of the 2881 e-mails delivered, 146 surgeons (5.1%) completed all seven scenarios. Most (129 of 131, 98%) were aware of MSLT-II and 125 (95%) found it practice-changing. Specifically, 52% (65 of 125) always, 40% usually, 6% rarely, and 3% never offered CLND before MSLT-II. Meanwhile, 4% always, 9% usually, 78% rarely, and 8% never offer CLND now, after MSLT-II (p < .0001). The most important clinicopathologic factors in determining CLND recommendations were extracapsular extension, number of positive SLN, and SLN tumor deposit size, while primary tumor mitotic index and nodal basin location were the least important. Surgical oncology fellowship training, melanoma patient volume, and academic center practice also influenced CLND recommendations. CONCLUSIONS: Most surgeon respondents are aware of MSLT-II, but its application in practice varies according to several clinicopathologic and surgeon factors.

Biochemical and hematological biomarkers of reproductive failure in bottlenose dolphins Tursiops truncatus.

The physiological demands of pregnancy inevitably result in alterations in both biochemical and hematological parameters as fetal development occurs. The shifts observed in successful pregnancy in bottlenose dolphins Tursiops truncatus to support both fetal physiological needs and maternal basal requirements have been established according to each trimester. Detecting aberrations in blood-based biomarkers could help facilitate diagnosis of gestational abnormalities, improve our understanding of factors influencing reproductive outcomes and aid in prediction of reproductive failure. This study retrospectively analyzed 263 blood samples from 15 bottlenose dolphins in 21 failed pregnancies over 28 yr (1989-2017). Most samples remained within normal pregnancy reference ranges; however, significant shifts were observed between trimesters. Hematological alterations, compared to successful pregnancy reference ranges from previously published data, were consistent across failed pregnancies and included an increased prevalence of elevated 2nd and 3rd trimester neutrophils, elevated 2nd trimester monocytes and decreased 3rd trimester eosinophils. In addition, low hematocrit and low red blood cells were more prevalent in the 2nd trimester. Biochemical shifts included an increased prevalence of elevated creatine phosphokinase in the 3rd trimester outside of the normal reference ranges. Across failed pregnancies, calcium and iron were decreased in the 3rd trimester. Significantly decreased progesterone in the 3rd trimester was a negative prognostic indicator of pregnancy outcome with decreasing 3rd trimester progesterone associated with failed pregnancy. This study demonstrates the use of blood-based biomarkers as possible predictors of pregnancy outcome in bottlenose dolphins.

Genomic expression assay testing among American Indian and Alaska Native women with breast cancer.

BACKGROUND: Breast cancer is one of the most common causes of cancer mortality for all women, including American Indian and Alaska Native (AI/AN) women. The use of the 21-gene recurrence score (RS) appears to be predictive of the benefit of chemotherapy for women with estrogen receptor (ER)-positive breast cancer. The objective of the current study was to compare RS testing between AI/AN and non-Hispanic White (NHW) women with breast cancer. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify women with ER-positive breast cancer from 2004 through 2015. Multivariable logistic regression was used to evaluate factors associated with RS use, with high-risk RS, and with chemotherapy use among those with a high-risk RS. RESULTS: A total of 363,387 NHW patients and 1951 AI/AN patients with ER-positive breast cancer were identified. AI/AN women were found to be less likely to undergo RS testing and, when tested, were more likely to have a high-risk RS. In the multivariable logistic regression analysis, AI/AN women were found to be significantly more likely to have a high-risk RS (odds ratio,1.28; 95% confidence interval, 1.01-1.66). Among untested women, chemotherapy use was higher for AI/AN women; however, the use of chemotherapy was not found to be significantly different between the groups with a high-risk RS. Using Cox proportional hazards models, AI/AN race was found to be significantly associated with worse overall survival. CONCLUSIONS: AI/AN women were less likely to undergo RS testing compared with NHW women and were more likely to have a high-risk RS. Reversing the disparity in genomic expression assay testing is critical to ensure guideline-based breast cancer treatment and improve survival rates for AI/AN women with breast cancer.

Minimally invasive microwave ablation provides excellent long-term outcomes for otherwise inaccessible hepatocellular cancer.

BACKGROUND AND OBJECTIVES: Thermal ablation can be used as a bridge to transplant or with curative intent for hepatocellular carcinoma (HCC). We report our experience with laparoscopic ablation of HCC in patients deemed inaccessible by the percutaneous approach. METHODS: We performed a retrospective review of surgical ablations from 2009 to 2017. Patient demographics, disease and treatment characteristics, and outcomes were abstracted from the medical record. Kaplan-Meier modeling was performed for survival and recurrence. RESULTS: Thirty-three patients were included with a median age of 62 (interquartile range [IQR], 57-67). Most patients were male (76%) and Caucasian (70%). Ninety-seven percent had underlying cirrhosis. Median model for end stage liver disease-sodium was 9.5 (IQR, 8-12). The median maximal diameter of ablated lesions was 2.6 cm (IQR, 1.8-3.0). Thirty-nine lesions were ablated; 97% were completed laparoscopically. The median maximal diameter of the ablation zone was 4.8 cm (IQR, 3.8-5.7) with a median difference of ablation zone to the tumor of 2.0 cm (IQR, 1.5-2.75). Twelve patients received additional treatment. Median disease-free survival was 66.7 months and median follow-up 42.9 months. Disease recurrence occurred in 13 patients (39%)-systemic recurrence in 6%, intrahepatic recurrence in 27% and local recurrence in 6%. CONCLUSION: Laparoscopic thermal ablation of HCC is safe and provides good oncologic outcomes for otherwise inaccessible tumors.

Misaligned protoplanetary disks in a young binary star system.

Many extrasolar planets follow orbits that differ from the nearly coplanar and circular orbits found in our Solar System; their orbits may be eccentric or inclined with respect to the host star's equator, and the population of giant planets orbiting close to their host stars suggests appreciable orbital migration. There is at present no consensus on what produces such orbits. Theoretical explanations often invoke interactions with a binary companion star in an orbit that is inclined relative to the planet's orbital plane. Such mechanisms require significant mutual inclinations between the planetary and binary star orbital planes. The protoplanetary disks in a few young binaries are misaligned, but often the measurements of these misalignments are sensitive only to a small portion of the inner disk, and the three-dimensional misalignment of the bulk of the planet-forming disk mass has hitherto not been determined. Here we report that the protoplanetary disks in the young binary system HK Tauri are misaligned by 60 to 68 degrees, such that one or both of the disks are significantly inclined to the binary orbital plane. Our results demonstrate that the necessary conditions exist for misalignment-driven mechanisms to modify planetary orbits, and that these conditions are present at the time of planet formation, apparently because of the binary formation process.