Pistil Mating Type and Morphology Are Mediated by the Brassinosteroid Inactivating Activity of the S-Locus Gene BAHD in Heterostylous Turnera Species.

Heterostyly is a breeding system that promotes outbreeding through a combination of morphological and physiological floral traits. In Turnera these traits are governed by a single, hemizygous S-locus containing just three genes. We report that the S-locus gene, BAHD, is mutated and encodes a severely truncated protein in a self-compatible long homostyle species. Further, a self-compatible long homostyle mutant possesses a T. krapovickasii BAHD allele with a point mutation in a highly conserved domain of BAHD acyl transferases. Wild type and mutant TkBAHD alleles were expressed in Arabidopsis to assay for brassinosteroid (BR) inactivating activity. The wild type but not mutant allele caused dwarfism, consistent with the wild type possessing, but the mutant allele having lost, BR inactivating activity. To investigate whether BRs act directly in self-incompatibility, BRs were added to in vitro pollen cultures of the two mating types. A small morph specific stimulatory effect on pollen tube growth was found with 5 µM brassinolide, but no genotype specific inhibition was observed. These results suggest that BAHD acts pleiotropically to mediate pistil length and physiological mating type through BR inactivation, and that in regard to self-incompatibility, BR acts by differentially regulating gene expression in pistils, rather than directly on pollen.

Monitoring System-Based Flying IoT in Public Health and Sports Using Ant-Enabled Energy-Aware Routing.

In recent decades, the Internet of flying networks has made significant progress. Several aerial vehicles communicate with one another to form flying ad hoc networks. Unmanned aerial vehicles perform a wide range of tasks that make life easier for humans. However, due to the high frequency of mobile flying vehicles, network problems such as packet loss, latency, and perhaps disrupted channel links arise, affecting data delivery. The use of UAV-enabled IoT in sports has changed the dynamics of tracking and working on player safety. WBAN can be merged with aerial vehicles to collect data regarding health and transfer it to a base station. Furthermore, the unbalanced energy usage of flying things will result in earlier mission failure and a rapid decline in network lifespan. This study describes the use of each UAV's residual energy level to ensure a high level of safety using an ant-based routing technique called AntHocNet. In health care, the use of IoT-assisted aerial vehicles would increase operational performance, surveillance, and automation optimization to provide a smart application of flying IoT. Apart from that, aerial vehicles can be used in remote communication for treatment, medical equipment distribution, and telementoring. While comparing routing algorithms, simulation findings indicate that the proposed ant-based routing protocol is optimal.

Bactericidal efficiency of micro- and nanostructured surfaces: a critical perspective.

Micro/nanostructured surfaces (MNSS) have shown the ability to inactivate bacterial cells by physical means. An enormous amount of research has been conducted in this area over the past decade. Here, we review the various surface factors that affect the bactericidal efficiency. For example, surface hydrophobicity of the substrate has been accepted to be influential on the bactericidal effect of the surface, but a review of the literature suggests that the influence of hydrophobicity differs with the bacterial species. Also, various bacterial viability quantification methods on MNSS are critically reviewed for their suitability for the purpose, and limitations of currently used protocols are discussed. Presently used static bacterial viability assays do not represent the conditions of which those surfaces could be applied. Such application conditions do have overlaying fluid flow, and bacterial behaviours are drastically different under flow conditions compared to under static conditions. Hence, it is proposed that the bactericidal effect should be assessed under relevant fluid flow conditions with factors such as shear stress and flowrate given due significance. This review will provide a range of opportunities for future research in design and engineering of micro/nanostructured surfaces with varying experimental conditions.

Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

The long and short of the S-locus in Turnera (Passifloraceae).

Distyly is an intriguing floral adaptation that increases pollen transfer precision and restricts inbreeding. It has been a model system in evolutionary biology since Darwin. Although the S-locus determines the long- and short-styled morphs, the genes were unknown in Turnera. We have now identified these genes. We used deletion mapping to identify, and then sequence, BAC clones and genome scaffolds to construct S/s haplotypes. We investigated candidate gene expression, hemizygosity, and used mutants, to explore gene function. The s-haplotype possessed 21 genes collinear with a region of chromosome 7 of grape. The S-haplotype possessed three additional genes and two inversions. TsSPH1 was expressed in filaments and anthers, TsYUC6 in anthers and TsBAHD in pistils. Long-homostyle mutants did not possess TsBAHD and a short-homostyle mutant did not express TsSPH1. Three hemizygous genes appear to determine S-morph characteristics in T. subulata. Hemizygosity is common to all distylous species investigated, yet the genes differ. The pistil candidate gene, TsBAHD, differs from that of Primula, but both may inactivate brassinosteroids causing short styles. TsYUC6 is involved in auxin synthesis and likely determines pollen characteristics. TsSPH1 is likely involved in filament elongation. We propose an incompatibility mechanism involving TsYUC6 and TsBAHD.

A novel discharge pathway for patients with advanced cancer requiring home parenteral nutrition.

BACKGROUND: The use of home parenteral nutrition (HPN) for palliative indications is increasing internationally and is the leading indication in some countries. Discharge on HPN can be complex in metabolically unstable patients and requires intestinal failure expertise. METHODS: Between 2012 and 2018, we performed a retrospective analysis aiming to assess the impact of a novel remote discharge pathway for palliative HPN patients. This was evaluated using a quality improvement approach. RESULTS: One hundred and twenty-five patients with active malignancy [mean (range) age 58 (25-80) years] were referred to the intestinal failure unit (IFU) for remote discharge. Of 82 patients were discharged from the oncology Centre on HPN using the pathway. The remaining 43 patients either declined HPN or the Oncology team felt that the patient became too unwell for HPN or died prior to discharge. There was an increase in patients referred for remote discharge from 13 in 2012 to 43 in 2017. The mean number of days between receipt of referral by the IFU to discharge on HPN from the oncology centre reduced from 29.4 days to 10.1 days. Following remote discharge, the mean number of days on HPN was 215.9 days. Catheter-related blood stream infection rates in this cohort were very low at 0.169 per 1000 catheter days. CONCLUSIONS: This is the first study to demonstrate the remote safe, effective and rapid discharge of patients requiring palliative HPN between two hospital sites. This allows patients with a short prognosis more time in their desired location.

Replicating carbonaceous vug in synthetic porous media.

This paper presents an alternative method of creating vuggy glass-bead core proxies, which can be used to investigate the effects of pore-scale features on carbonate petrophysical properties. Carbonates are complex rocks having a widespread variation in pore type, size, distribution, and porosity. With this method we can control vug shape, size, and position. Homogeneous glass bead core proxies are sintered using 1.0 mm diameter glass beads in a muffle furnace. Vugs are 3D-printed in plastic and used to make a mold in Play-Doh®; which is cast in gypsum cement and used as a placeholder during the sintering process. The gypsum vug dissolves during acid flood, leaving an empty space inside the glass matrix. Computed tomography (CT) scans are made of the acid washed vug space and compared to the 3D model.

Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study.

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. Clinical trials.gov: NCT01991210.

Rapid Analysis of Outcomes Using the Systemic Anti-Cancer Therapy (SACT) Dataset.

We audited the accuracy of the Systemic Anti-Cancer Therapy dataset as a resource for rapid analysis of outcomes for patients, in this example, receiving Cancer Drug Fund funded monoclonal antibodies to treat metastatic colorectal cancer. We concluded that the Systemic Anti-Cancer Therapy dataset is a potentially valuable resource for rapidly determining survival outcome for patients treated with chemotherapy.

Does clinical trial participation improve outcomes in patients with ovarian cancer?

INTRODUCTION: Treatment on a clinical trial is considered to be beneficial to oncology patients. However, supportive evidence for this is scarce. Trial effect describes the phenomenon of improved health outcomes in patients treated with standard of care (SOC) on trial compared to those receiving SOC outside of a clinical trial. We evaluated trial effect in patients with ovarian cancer treated at our tertiary cancer centre. METHODS: We performed a retrospective cohort study of patients with ovarian cancer treated at The Christie National Health Service Foundation Trust. Patients treated on one of three first-line clinical trials: (SCOTROC-4, ICON-5, ICON-7) were matched (for age, International Federation of Gynaecology and Obstetrics stage, surgical status and performance status) with individuals receiving the same SOC off trial. Survival was calculated using Kaplan-Meier methodology. RESULTS: 60 patients were evaluated; 30 on trial and 30 on SOC off trial. The median progression-free survival (PFS) was 21.8 months (control group) and 25.9 months (trial group), median overall survival (OS) was 64.3 months (control group) and 68.9 months (trial group). There was no difference in PFS (log-rank test: HR 0.87 (95% CI 0.48 to 1.54), p=0.6) or OS (log-rank test: HR 0.87 (95% CI 0.46 to 1.64), p=0.7) between groups. CONCLUSIONS: Patient survival was similar regardless if treated on trial or as SOC. Our findings do not support trial effect, at least in a tertiary cancer centre. Clinical trial participation in specialised cancer centres promotes best practice to the benefit of all patients. These findings may impact discussions round consent of patients to trials and organisation of oncology services.

Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK.

AIMS: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. MATERIALS AND METHODS: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. RESULTS: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9-73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. CONCLUSION: The data suggest that international survival statistics are achieved in UK regional cancer centres.

Mortality within 30 days following systemic anti-cancer therapy, a review of all cases over a 4 year period in a tertiary cancer centre.

BACKGROUND: The national confidential enquiry into patient outcomes and death (NCEPOD) set important benchmarks in assessing the quality of care received by patients dying within 30 days of systemic anticancer therapy (SACT). Monthly morbidity and mortality audits conducted to recommendations in the NCEPOD were commenced at the Christie NHS Foundation Trust in 2009, specifically to assess and improve patient outcomes. METHODS: We evaluated the outcomes of patients who died within 30 days of SACT over a 4 year period 2009-2013. We collated audit findings to determine the number of treatment related deaths, clinical characteristics of patients, causes of death and quality of care received. We examined the benefit of the audit in decreasing 30 day mortality during the 4 years and considered factors that may be associated with an increased risk of SACT related death. RESULTS: A total of 31,183 patients were treated at the Christie from 2009 to 2013. Of these 4% died within 30 days of SACT. Death was treatment related in 11%. The decision to treat with SACT was appropriate in 87% of but there was room for improvement in care in 24%. Mortality decreased over the 4 years. Possible factors associated with 30 day mortality post SACT included performance status ⩾2, presence of comorbidities, treatment type and treatment setting. CONCLUSIONS: We demonstrated that our audit process is feasible and robust. Further areas of research to determine predictive scores for patient treatment selection and improve outcomes were highlighted and are ongoing.

Primary central nervous system amelanotic melanoma in a Hispanic male: Case report.

BACKGROUND: Primary melanotic neoplasms of the central nervous system (CNS) are uncommon; amelanotic melanomas in this region are extremely rare. Very few cases of amelanotic variation of primary melanoma in the CNS were reported on. General guidelines or recommendations to establish this diagnosis do not exist. CASE REPORT: A sixty-year-old male Hispanic patient presented with a 7-day history of numbness and dizziness. Initial laboratory work-up and physical examination were inconclusive. Cerebral radiological imaging showed a left frontal lesion. Further work-up after clinical deterioration revealed an increase in the lesion size consistent with hemorrhage and changes in T1WI. Biopsy and immunochemistry demonstrated the presence of amelanotic melanoma in the CNS without evidence of another primary lesion. CONCLUSIONS: Primary amelanotic melanoma of the CNS represents a challenge, clinically and diagnostically. Magnetic resonance imaging can be helpful in early stages. Final diagnosis is established with immunohistochemical testing. Physicians should be aware of the existence of this rare manifestation and difficulties faced while building this diagnosis.

Moyamoya in Hispanics: not Only in Japanese.

Moyamoya disease was first described in 1957 as hypoplasia of the bilateral internal carotid arteries, the characteristic appearance of the associated network of abnormally dilated collateral vessels on angiography was later likened to something hazy, like a puff of cigarette smoke, which, in Japanese, is moyamoya. This paper describes two cases of moyamoya presentations, including moyamoya disease and moyamoya syndrome. Moyamoya may rarely occur in North American Hispanic patients. The presentation can vary significantly and ranges bwtween fulminant outcome and prolonged survival. Awareness about moyamoya and its different presentations may be beneficial for the patients and can improve the outcome.

Thrombosis in ovarian cancer: a case control study.

BACKGROUND: Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies. METHODS: A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis. RESULTS: Ninety-nine thrombotic events occurred in 90 patients (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking in the 4 months following diagnosis. Patients with thrombosis were older (mean 65 vs 61 years, P=0.007), had a worse performance status (PS ≥2: 29.9% vs 9.5%, P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%, P<0.0001) than patients without thrombosis. Shorter overall survival was seen in patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than without thrombosis (P=0.001). When the control group was matched for stage and PS, no survival difference was seen (P=0.91). CONCLUSION: Ovarian cancer patients with thrombotic events had a shorter survival. However, when matched for prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.

Accessing cancer services in North West England: the Chinese population.

Relatively few Chinese patients access tertiary cancer services in North West England. We investigated the reasons behind this using a culturally sensitive questionnaire. The questionnaire, completed by 214 Chinese people in English, Cantonese or Mandarin, evaluated the Chinese population's access and satisfaction with primary care, understanding of cancer and awareness of local cancer services. Ninety-five per cent of respondents were registered with a general practitioner (GP) and 75% had accessed primary care in the last year. Satisfaction with GP consultations was high but a third of respondents reported a lack of confidence in local National Health Service (NHS) services. Only 57% of eligible women had attended cervical screening programmes. The overall understanding of the causes and treatment of cancer and cancer services in the North West was poor. Despite registration with primary healthcare, the Chinese population under-utilise cancer prevention programmes and tertiary cancer services because of a lack of awareness and understanding of cancer services in the North West. A significant proportion of the population is dissatisfied with the perceived slow service and lack confidence in services, with 41% considering using healthcare abroad. These data highlight the critical need to engage with, educate and support the Chinese population if they are to access NHS cancer services.

Multicystic dysplastic kidney complicated by pyelonephritis.

PATIENT: Female, 21 FINAL DIAGNOSIS: Multicystic Dysplastic Kidney Disease complicated by pyelonephritis Symptoms: Left flank pain (CVAT) • dysuria • fever MEDICATION: Levofloxacin Clinical Procedure: Dimercaptosuccinic acid scan • voiding cystouretrogram Specialty: Nephrology. OBJECTIVE: Rare disease. BACKGROUND: Multicystic dysplastic kidney (MCDK) is a renal dysplasia characterized by the presence of multiple cysts that are non-communicating, separated by dysplastic parenchyma that consumes the renal cortex resulting in a nonfunctional kidney. MCDK has an incidence of 1: 4300 of live births and is usually unilateral, most commonly occurring in the left kidney. Simple MCDK is defined as unilateral dysplasia with a normal contralateral kidney but with compensatory hypertrophy of the contralateral kidney, and no associated genitourinary anomalies. CASE REPORT: A 21 year old Hispanic American female, presented with intermittent, sharp, severe left flank pain, fever and dysuria for two days but had gradually worsened within the last 24 hours prior to presentation. Previous history of multicystic dysplastic kidney, diagnosed four years ago. No pertinent physical examination findings except left costovertebral angle tenderness (CVAT). Urinalysis findings were positive for infection and urine culture grew pan sensitive Escherichia coli. A CT scan of abdominal and pelvis without contrast revealed a normal right kidney and left kidney had multiple non-communicating dilated cystic spaces, but no hydronephrosis, left ureteropelvic junction obstruction and finding were consistent with multicystic dysplastic kidney and also noted perinephric stranding. CONCLUSIONS: VUR is the most common renal abnormality in patients with MCDK, occurring in about 25% of contralateral kidney. Infections involving the MCDK are rare. In fact, cases of infections such as pyelonephritis or an infected renal cyst of MCDK are almost non-existent in the current literature. This patient presented with findings consistent with MCDK complicated by pyelonephritis.

Bacterial attachment on sub-nanometrically smooth titanium substrata.

Despite the volume of work that has been conducted on the topic, the role of surface topography in mediating bacterial cell adhesion is not well understood. The primary reason for this lack of understanding is the relatively limited extent of topographical characterisation employed in many studies. In the present study, the topographies of three sub-nanometrically smooth titanium (Ti) surfaces were comprehensively characterised, using nine individual parameters that together describe the height, shape and distribution of their surface features. This topographical analysis was then correlated with the adhesion behaviour of the pathogenic bacteria Staphylococcus aureus and Pseudomonas aeruginosa, in an effort to understand the role played by each aspect of surface architecture in influencing bacterial attachment. While P. aeruginosa was largely unable to adhere to any of the three sub-nanometrically smooth Ti surfaces, the extent of S. aureus cell attachment was found to be greater on surfaces with higher average, RMS and maximum roughness and higher surface areas. The cells also attached in greater numbers to surfaces that had shorter autocorrelation lengths and skewness values that approached zero, indicating a preference for less ordered surfaces with peak heights and valley depths evenly distributed around the mean plane. Across the sub-nanometrically smooth range of surfaces tested, it was shown that S. aureus more easily attached to surfaces with larger features that were evenly distributed between peaks and valleys, with higher levels of randomness. This study demonstrated that the traditionally employed amplitudinal roughness parameters are not the only determinants of bacterial adhesion, and that spatial parameters can also be used to predict the extent of attachment.

A rare case of renal recovery in a young patient with multiple myeloma.

Multiple myeloma (MM) is an uncommon hematologic malignancy accounting for 1% of all malignancies. Renal involvement is a common complication of MM. Rapid intervention to reverse renal dysfunction may be critical for management, especially in patients with light chain cast nephropathy. Recovery rate ranges from 5% to 15%. We describe an atypical presentation of MM in a young patient who presented with severe renal insufficiency requiring renal replacement therapy and achieved complete renal recovery with chemotherapy.

Nature inspired structured surfaces for biomedical applications.

Nature has created an array of superhydrophobic surfaces that possess water-repellent, self-cleaning and anti-icing properties. These surfaces have a number of potential applications in the biomedical industry, as they have the potential to control protein adsorption and cell adhesion. Natural superhydrophobic surfaces are typically composed of materials with a low intrinsic surface free-energy (e.g the cuticular waxes of lotus leaves and insect wings) with a hierarchical structural configuration. This hierarchical surface topography acts to decrease the contact area of water droplets in contact with the surface, thereby increasing the extent of the air/water interface, resulting in water contact angles greater than 150º. In order to employ these surfaces in biotechnological applications, fabrication techniques must be developed so that these multi-scale surface roughness characteristics can be reproduced. Additionally, these fabrication techniques must also be able to be applied to the material required for the intended application. An overview of some of the superhydrophobic surfaces that exist in nature is presented, together with an explanation of the theories of their wettability. Also included is a description of some of the biomedical applications of superhydrophobic surfaces and fabrication techniques that can be used to mimic superhydrophobic surfaces found in nature.