Obturator Nerve Injury in Robotic Pelvic Surgery: Scenarios and Management Strategies.

BACKGROUND: Obturator nerve injury (ONI) is an uncommon complication of pelvic surgery, usually reported in 0.2-5.7% of cases undergoing surgical treatment of urological and gynecological malignancies involving pelvic lymph node dissection (PLND). OBJECTIVE: To describe how an ONI may occur during robotic pelvic surgery and the corresponding management strategies. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed video content on intraoperative ONI provided by robotic surgeons from high-volume centers. SURGICAL PROCEDURE: ONI was identified during PLND and managed according to the type of nerve injury. RESULTS AND LIMITATIONS: The management approach varies with the type of injury. Crush injury frequently occurs at an advanced stage of PLND. For a crush injury to the obturator nerve caused by a clip, management only requires its safe removal. Three situations can occur if the nerve is transected: (1) transection with feasible approximation and tension-free nerve anastomosis; (2) transection with challenging approximation requiring certain strategies for proper nerve anastomosis; and (3) transection with a hidden proximal nerve ending that may initially appear intact, but is clearly injured when revealed by further dissection. Each case has different management strategies with a common aim of prompt repair of the anatomic disruption to restore proper nerve conduction. CONCLUSIONS: ONI is a preventable complication that requires proper identification of the anatomy and high-risk areas when performing pelvic lymph node dissection. Prompt intraoperative recognition and repair using the management strategies described offer patients the best chance of recovery without sequelae. PATIENT SUMMARY: We describe the different ways in which the obturator nerve in the pelvic area can be damaged during urological or gynecological surgeries. This is a preventable complication and we describe how it can be avoided and different management options, depending on the type of nerve injury.

Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.

Concentric pulmonary vascular wall thickening due partially to increased pulmonary artery (PA) smooth muscle cell (PASMC) proliferation contributes to elevating pulmonary vascular resistance (PVR) in patients with pulmonary hypertension (PH). Although pulmonary vasoconstriction may be an early contributor to increasing PVR, the transition of contractile PASMCs to proliferative PASMCs may play an important role in the development and progression of pulmonary vascular remodeling in PH. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) is a trigger for PASMC contraction and proliferation. Here, we report that upregulation of Piezo1, a mechanosensitive cation channel, is involved in the contractile-to-proliferative phenotypic transition of PASMCs and potential development of pulmonary vascular remodeling. By comparing freshly isolated PA (contractile PASMCs) and primary cultured PASMCs (from the same rat) in a growth medium (proliferative PASMCs), we found that Piezo1, Notch2/3, and CaSR protein levels were significantly higher in proliferative PASMCs than in contractile PASMCs. Upregulated Piezo1 was associated with an increase in expression of PCNA, a marker for cell proliferation, whereas downregulation (with siRNA) or inhibition (with GsMTx4) of Piezo1 attenuated PASMC proliferation. Furthermore, Piezo1 in the remodeled PA from rats with experimental PH was upregulated compared with PA from control rats. These data indicate that PASMC contractile-to-proliferative phenotypic transition is associated with the transition or adaptation of membrane channels and receptors. Upregulated Piezo1 may play a critical role in PASMC phenotypic transition and PASMC proliferation. Upregulation of Piezo1 in proliferative PASMCs may likely be required to provide sufficient Ca2+ to assure nuclear/cell division and PASMC proliferation, contributing to the development and progression of pulmonary vascular remodeling in PH.

TRPC6, a therapeutic target for pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (PAH) is a fatal and progressive disease. Sustained vasoconstriction due to pulmonary arterial smooth muscle cell (PASMC) contraction and concentric arterial remodeling due partially to PASMC proliferation are the major causes for increased pulmonary vascular resistance and increased pulmonary arterial pressure in patients with precapillary pulmonary hypertension (PH) including PAH and PH due to respiratory diseases or hypoxemia. We and others observed upregulation of TRPC6 channels in PASMCs from patients with PAH. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) in PASMC triggers PASMC contraction and vasoconstriction, while Ca2+-dependent activation of PI3K/AKT/mTOR pathway is a pivotal signaling cascade for cell proliferation and gene expression. Despite evidence supporting a pathological role of TRPC6, no selective and orally bioavailable TRPC6 antagonist has yet been developed and tested for treatment of PAH or PH. In this study, we sought to investigate whether block of receptor-operated Ca2+ channels using a nonselective blocker of cation channels, 2-aminoethyl diphenylborinate (2-APB, administered intraperitoneally) and a selective blocker of TRPC6, BI-749327 (administered orally) can reverse established PH in mice. The results from the study show that intrapulmonary application of 2-APB (40 µM) or BI-749327 (3-10 µM) significantly and reversibly inhibited acute alveolar hypoxia-induced pulmonary vasoconstriction. Intraperitoneal injection of 2-APB (1 mg/kg per day) significantly attenuated the development of PH and partially reversed established PH in mice. Oral gavage of BI-749327 (30 mg/kg, every day, for 2 wk) reversed established PH by ∼50% via regression of pulmonary vascular remodeling. Furthermore, 2-APB and BI-749327 both significantly inhibited PDGF- and serum-mediated phosphorylation of AKT and mTOR in PASMC. In summary, the receptor-operated and mechanosensitive TRPC6 channel is a good target for developing novel treatment for PAH/PH. BI-749327, a selective TRPC6 blocker, is potentially a novel and effective drug for treating PAH and PH due to respiratory diseases or hypoxemia.

Disparities in utilization of outpatient surgical care among children.

BACKGROUND: The purpose of this study was to quantify disparities in the utilization of outpatient pediatric surgical care and to examine the extent to which neighborhood-level socioeconomic disadvantage is associated with access to care among children. METHODS: Clinic "no-shows" were examined among children scheduled from 2017 to 2019 at seven pediatric surgery clinics associated with a tertiary care children's hospital. The association between Area Deprivation Index, a neighborhood-level measure of socioeconomic disadvantage, and other patient factors with clinic no-shows was examined using multivariable logistic regression models. Difficulties in accessing postoperative care in particular were explored in a subgroup analysis of postoperative (within 90 days) clinic visits after appendectomy or inguinal/umbilical hernia repairs. RESULTS: Among 10,162 patients, 16% had at least 1 no-show for a clinic appointment. Area Deprivation Index (most deprived decile adjusted odds ratio 3.17, 95% confidence interval 2.20-4.58, P < .001), Black race (adjusted odds ratio 3.30, 95% confidence interval 2.70-4.00, P < .001), and public insurance (adjusted odds ratio 2.75, 95% confidence interval 2.38-3.31, P < .001) were associated with having at least 1 no-show. Similar associations were identified among 2,399 children scheduled for postoperative clinic visits after undergoing appendectomy or inguinal/umbilical hernia repair, among whom 20% were a no-show. CONCLUSION: Race, insurance type, and neighborhood-level socioeconomic disadvantage are associated with disparities in utilization of outpatient pediatric surgical care. Challenges accessing routine outpatient care among disadvantaged children may be one mechanism through which disparate outcomes result among children requiring surgical care.

Development and validation of an objective scoring tool to evaluate surgical dissection: Dissection Assessment for Robotic Technique (DART).

Purpose: Evaluation of surgical competency has important implications for training new surgeons, accreditation, and improving patient outcomes. A method to specifically evaluate dissection performance does not yet exist. This project aimed to design a tool to assess surgical dissection quality. Methods: Delphi method was used to validate structure and content of the dissection evaluation. A multi-institutional and multi-disciplinary panel of 14 expert surgeons systematically evaluated each element of the dissection tool. Ten blinded reviewers evaluated 46 de-identified videos of pelvic lymph node and seminal vesicle dissections during the robot-assisted radical prostatectomy. Inter-rater variability was calculated using prevalence-adjusted and bias-adjusted kappa. The area under the curve from receiver operating characteristic curve was used to assess discrimination power for overall DART scores as well as domains in discriminating trainees (≤100 robotic cases) from experts (>100). Results: Four rounds of Delphi method achieved language and content validity in 27/28 elements. Use of 3- or 5-point scale remained contested; thus, both scales were evaluated during validation. The 3-point scale showed improved kappa for each domain. Experts demonstrated significantly greater total scores on both scales (3-point, p< 0.001; 5-point, p< 0.001). The ability to distinguish experience was equivalent for total score on both scales (3-point AUC= 0.92, CI 0.82-1.00, 5-point AUC= 0.92, CI 0.83-1.00). Conclusions: We present the development and validation of Dissection Assessment for Robotic Technique (DART), an objective and reproducible 3-point surgical assessment to evaluate tissue dissection. DART can effectively differentiate levels of surgeon experience and can be used in multiple surgical steps.

Predictive Risk Factors for Continued Smoking after the Diagnosis of a Genitourinary Malignancy.

OBJECTIVE: To determine risk factors for continued smoking following a diagnosis of a genitourinary (GU) malignancy. Smoking is a well established risk factor in the development of cancers involving the GU tract. Unfortunately, a large percentage of patients continue to smoke or relapse after cancer diagnosis; by doing so, there is an increased risk of recurrence, poor survival rates, treatment complications, secondary primary cancers, and other chronic smoking related illnesses. MATERIALS AND METHODS: Two hundred and five patients who presented to a Urologic Oncology clinic at a single tertiary treatment center were given smoking cessation counseling and pharmacotherapy, as well as a questionnaire which was used to identify smoking status, demographics, and behavioral/psychosocial characteristics. Patients were followed for a minimum of 1 year with a median length of follow up for 13 months. RESULTS: 91% of patients enrolled in the study continued smoking at survey completion. After accounting for age, ethnicity, education and cigarettes consumed/day, 5 variables were independently associated with an increased risk of continued smoking: smoking 20 or more cigarettes per day, less than 2 prior quit attempts, anxiety and/or depression, fear of cancer recurrence, and home secondhand smoke exposure. CONCLUSION: The role of the urologist is imperative for encouraging smoking cessation. While every patient should receive adequate counseling regarding smoking at the time of a GU malignancy diagnosis, identifying patients with the risk factors noted in this study and augmenting smoking cessation efforts may result in stronger efforts to quit and prevention of long-term complications.

Reactions to Multiple Ascending Doses of the Microtubule Stabilizer TPI-287 in Patients With Alzheimer Disease, Progressive Supranuclear Palsy, and Corticobasal Syndrome: A Randomized Clinical Trial.

Importance: Basket-design clinical trials that allow investigation of treatment effects on different clinical syndromes that share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. Objective: To assess the safety, tolerability, and pharmacodynamics of the microtubule stabilizer TPI-287 (abeotaxane) in Alzheimer disease (AD) or the 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Design, Setting, and Participants: Two parallel-design, double-blind, placebo-controlled phase 1 randomized clinical trials in AD and 4RT were conducted from December 20, 2013, through May 4, 2017, at the University of California, San Francisco, and University of Alabama at Birmingham. A total of 94 patients with clinically diagnosed AD (n = 39) and 4RT (n = 55) were screened; of these, 3 refused to participate, and 10 with AD and 11 with 4RT did not meet inclusion criteria. A total of 29 patients with AD, 14 with PSP, and 30 with ß-amyloid-negative CBS (determined on positron emission tomography findings) were enrolled. Data were analyzed from December 20, 2013, through May 4, 2017, based on modified intention to treat. Interventions: Randomization was 8:3 drug to placebo in 3 sequential dose cohorts receiving 2.0, 6.3, or 20.0 mg/m2 of intravenous TPI-287 once every 3 weeks for 9 weeks, with an optional 6-week open-label extension. Main Outcomes and Measures: Primary end points were safety and tolerability (maximal tolerated dose) of TPI-287. Secondary and exploratory end points included TPI-287 levels in cerebrospinal fluid (CSF) and changes on biomarker, clinical, and neuropsychology measures. Results: A total of 68 participants (38 men [56%]; median age, 65 [range, 50-85] years) were included in the modified intention-to-treat analysis, of whom 26 had AD (14 women [54%]; median age, 63 [range, 50-76] years), and 42 had 4RT (16 women [38%]; median age, 69 [range, 54-83] years). Three severe anaphylactoid reactions occurred in TPI-287-treated patients with AD, whereas none were seen in patients with 4RT, leading to a maximal tolerated dose of 6.3 mg/m2 for AD and 20.0 mg/m2 for 4RT. More falls (3 in the placebo group vs 11 in the TPI-287 group) and a dose-related worsening of dementia symptoms (mean [SD] in the CDR plus NACC FTLD-SB [Clinical Dementia Rating scale sum of boxes with frontotemporal dementia measures], 0.5 [1.8] in the placebo group vs 0.7 [1.6] in the TPI-287 group; median difference, 1.5 [95% CI, 0-2.5]; P = .03) were seen in patients with 4RT. Despite undetectable TPI-287 levels in CSF, CSF biomarkers demonstrated decreased chitinase-3-like protein-1 (YKL-40) levels in the 4RT treatment arm (mean [SD], -8.4 [26.0] ng/mL) compared with placebo (mean [SD], 10.4 [42.3] ng/mL; median difference, -14.6 [95% CI, -30.0 to 0.2] ng/mL; P = .048, Mann-Whitney test). Conclusions and Relevance: In this randomized clinical trial, TPI-287 was less tolerated in patients with AD than in those with 4RT owing to the presence of anaphylactoid reactions. The ability to reveal different tau therapeutic effects in various tauopathy syndromes suggests that basket trials are a valuable approach to tau therapeutic early clinical development. Trial Registration: ClinicalTrials.gov identifiers: NCT019666666 and NCT02133846.

Epithelioid angiomyolipoma metastasis to the rectus abdominis.

A 37-year-old female presented with abdominal pain. An abdominal computed tomography scan demonstrated a 10 cm x 13 cm left renal mass. An open adrenal-sparing radical nephrectomy was performed. The pathological diagnosis was epithelioid angiomyolipoma. Five-year surveillance did not demonstrate recurrence of disease. However, a 1.8 cm x 2.5 cm mass on the rectus abdominis muscle was identified after 5 years. Biopsy of the mass demonstrated histologic findings consistent with the primary tumor. Herein, we report a case of metastatic renal epithelioid angiomyolipoma to the rectus abdominis muscle more than 5 years after resection of primary renal tumor.

Usefulness of Preoperative Ultrasound for the Evaluation of Testicular Rupture in the Setting of Scrotal Gunshot Wounds.

PURPOSE: A scrotal gunshot wound may result in testicular injury, necessitating urgent scrotal exploration and attempted testicular salvage. Scrotal ultrasound is highly sensitive and specific for testicular rupture in the setting of blunt scrotal trauma but it has been poorly studied in the setting of scrotal gunshot wounds. Our objective was to determine the accuracy of scrotal ultrasound to identify testicular rupture following a scrotal gunshot wound. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with a scrotal gunshot wound from 2003 to 2014 in whom preoperative ultrasound was done prior to scrotal exploration. A heterogeneous echo pattern of testicular parenchyma with contour loss was considered a positive examination for testicular rupture. Patients underwent scrotal exploration within 24 hours of presentation. The sensitivity and specificity of ultrasound were estimated and compared to operative findings. ROC curve analysis was done. RESULTS: Of 75 patients who sustained a scrotal gunshot wound ultrasound was positive in 30 and negative in 45. No ultrasound revealed bilateral injuries. Scrotal exploration demonstrated a total of 40 testicular ruptures in 35 patients, of which 30 testicles were salvaged. Ten orchiectomies were performed. The sensitivity and specificity of ultrasound were 60% and 95%, respectively, with 16 missed injuries and 6 false-positive findings. Positive predictive value was 80% and negative predictive value was 87%. The ROC AUC was 0.79. In 6 of the 16 missed injuries there was an ipsilateral hematocele or hematoma. CONCLUSIONS: The sensitivity of scrotal ultrasound is limited for evaluating testicular rupture after a scrotal gunshot wound. Large coincident hematoceles or hematomas may obscure the diagnosis of testicular rupture. Negative ultrasound should not preclude scrotal exploration after a scrotal gunshot wound is sustained.

An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency from GRN gene mutations.

INTRODUCTION: Frontotemporal lobar degeneration-causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration-approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers. METHODS: We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints. RESULTS: There were no serious adverse events; however, PGRN concentrations (cerebrospinal fluid and plasma) did not change significantly following treatment (percent changes of -5.2 ± 10.9% in plasma and -10.2 ± 7.8% in cerebrospinal fluid). Measurable atrophy within the left middle frontal gyrus was observed over an 8-week period. DISCUSSION: While well tolerated, nimodipine treatment did not alter PGRN concentrations or secondary outcomes.

Quantifying the evidence for co-benefits between species conservation and climate change mitigation in giant panda habitats.

Conservationists strive for practical, cost-effective management solutions to forest-based species conservation and climate change mitigation. However, this is compromised by insufficient information about the effectiveness of protected areas in increasing carbon storage, and the co-benefits of species and carbon conservation remain poorly understood. Here, we present the first rigorous quantitative assessment of the roles of giant panda nature reserves (NRs) in carbon sequestration, and explore the co-benefits of habitat conservation and climate change mitigation. Results show that more than 90% of the studied panda NRs are effective in increasing carbon storage, with the mean biomass carbon density of the whole NRs exhibiting a 4.2% higher growth rate compared with lands not declared as NRs over the period 1988-2012, while this effectiveness in carbon storage masks important patterns of spatial heterogeneity across the giant panda habitats. Moreover, the significant associations have been identified between biomass carbon density and panda's habitat suitability in ~85% NRs and at the NR level. These findings suggest that the planning for carbon and species conservation co-benefits would enhance the greatest return on limited conservation investments, which is a critical need for the giant panda after its conservation status has been downgraded from "endangered" to "vulnerable".

Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection.

Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.

The cancer experience map: an approach to including the patient voice in supportive care solutions.

The perspective of the patient, also called the "patient voice", is an essential element in materials created for cancer supportive care. Identifying that voice, however, can be a challenge for researchers and developers. A multidisciplinary team at a health information company tasked with addressing this issue created a representational model they call the "cancer experience map". This map, designed as a tool for content developers, offers a window into the complex perspectives inside the cancer experience. Informed by actual patient quotes, the map shows common overall themes for cancer patients, concerns at key treatment points, strategies for patient engagement, and targeted behavioral goals. In this article, the team members share the process by which they created the map as well as its first use as a resource for cancer support videos. The article also addresses the broader policy implications of including the patient voice in supportive cancer content, particularly with regard to mHealth apps.

FTO, RNA epigenetics and epilepsy.

Several recent landmark papers describing N(6) -methyladenosine (m(6) A) RNA modifications have provided valuable new insights as to the importance of m(6) A in the RNA transcriptome and in furthering the understanding of RNA epigenetics. One endogenous enzyme responsible for demethylating RNA m(6) A, FTO, is highly expressed in the CNS and is likely involved in mRNA metabolism, splicing or other nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding transcripts that bind to target mRNAs and inhibit subsequent translation, are highly expressed in the CNS and are associated with several neurological disorders, including epilepsy. miRNAs frequently bind to recognition sequences in the 3'UTR, a region that is also enriched for m(6) A. Certain specific miRNAs are upregulated by neuronal activity and are coupled to epileptogenesis; these miRNAs contain a consensus m(6) A site that if methylated could possibly regulate miRNA processing or function. This commentary highlights aspects from recent papers to propose a functional association between FTO, RNA epigenetics and epilepsy.

Murine gamma-herpesvirus immortalization of fetal liver-derived B cells requires both the viral cyclin D homolog and latency-associated nuclear antigen.

Human gammaherpesviruses are associated with the development of lymphoproliferative diseases and B cell lymphomas, particularly in immunosuppressed hosts. Understanding the molecular mechanisms by which human gammaherpesviruses cause disease is hampered by the lack of convenient small animal models to study them. However, infection of laboratory strains of mice with the rodent virus murine gammaherpesvirus 68 (MHV68) has been useful in gaining insights into how gammaherpesviruses contribute to the genesis and progression of lymphoproliferative lesions. In this report we make the novel observation that MHV68 infection of murine day 15 fetal liver cells results in their immortalization and differentiation into B plasmablasts that can be propagated indefinitely in vitro, and can establish metastasizing lymphomas in mice lacking normal immune competence. The phenotype of the MHV68 immortalized B cell lines is similar to that observed in lymphomas caused by KSHV and resembles the favored phenotype observed during MHV68 infection in vivo. All established cell lines maintained the MHV68 genome, with limited viral gene expression and little or no detectable virus production - although virus reactivation could be induced upon crosslinking surface Ig. Notably, transcription of the genes encoding the MHV68 viral cyclin D homolog (v-cyclin) and the homolog of the KSHV latency-associated nuclear antigen (LANA), both of which are conserved among characterized γ2-herpesviruses, could consistently be detected in the established B cell lines. Furthermore, we show that the v-cyclin and LANA homologs are required for MHV68 immortalization of murine B cells. In contrast the M2 gene, which is unique to MHV68 and plays a role in latency and virus reactivation in vivo, was dispensable for B cell immortalization. This new model of gammaherpesvirus-driven B cell immortalization and differentiation in a small animal model establishes an experimental system for detailed investigation of the role of gammaherpesvirus gene products and host responses in the genesis and progression of gammaherpesvirus-associated lymphomas, and presents a convenient system to evaluate therapeutic modalities.

Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus.

The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50-60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse-adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse-adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine-origin 2009 H1N1 influenza virus.

Exploiting Incommensurate Symmetry Numbers: Rational Design and Assembly of M2 M3 'L6 Supramolecular Clusters with C3h Symmetry.

Mixed-metal mesocates [M2 Pd3 Br6 L6 ]4- (M=TiIV , SnIV ; L=4-diphenylphosphanyl-catecholate) have been synthesized, in which the two incommensurate symmetry elements generated by the different metal ions are linked by a rigid, bifunctional ligand to generate a C3h -symmetrical cluster (see picture).