An evaluation of CT radiation doses within the Yorkshire Lung Screening Trial.

OBJECTIVES: To evaluate radiation doses for all low-dose CT scans performed during the first year of a lung screening trial. METHODS: For all lung screening scans that were performed using a CT protocol that delivered image quality meeting the RSNA QIBA criteria, radiation dose metrics, participant height, weight, gender, and age were recorded. Values of volume CT dose index (CTDIvol) and dose length product (DLP) were evaluated as a function of weight in order to assess the performance of the scan protocol across the participant cohort. Calculated effective doses were used to establish the additional lifetime attributable cancer risks arising from trial scans. RESULTS: Median values of CTDIvol, DLP, and effective dose (IQR) from the 3521 scans were 1.1 mGy (0.70), 42.4 mGycm (24.9), and 1.15 mSv (0.67), whilst for 60-80kg participants the values were 1.0 mGy (0.30), 35.8 mGycm (11.4), and 0.97 mSv (0.31). A statistically significant correlation between CTDIvol and weight was identified for males (r = 0.9123, P < .001) and females (r = 0.9052, P < .001), however, the effect of gender on CTDIvol was not statistically significant (P = .2328) despite notable differences existing at the extremes of the weight range. The additional lifetime attributable cancer risks from a single scan were in the range 0.001%-0.006%. CONCLUSIONS: Low radiation doses can be achieved across a typical lung screening cohort using scan protocols that have been shown to deliver high levels of image quality. The observed dose levels may be considered as typical values for lung screening scans on similar types of scanners for an equivalent participant cohort. ADVANCES IN KNOWLEDGE: Presentation of typical radiation dose levels for CT lung screening examinations in a large UK trial. Effective radiation doses can be of the order of 1 mSv for standard sized participants. Lifetime attributable cancer risks resulting from a single low-dose CT scan did not exceed 0.006%.

The radiology quality assurance process in the Yorkshire Lung Screening Trial, and findings from the baseline round of low dose CT screening for lung cancer.

OBJECTIVE: As lung cancer screening is rolled-out, there is a need to develop an effective quality assurance (QA) framework around radiology reporting to ensure optimal implementation. Here, we report a structured QA process for low-dose CT (LDCT) scans performed in the Yorkshire Lung Screening Trial. METHODS: Negative LDCT scans were single read after using computer-aided detection software. The radiology QA process included reviewing 5% of negative scans selected at random, and all cases with a subsequent diagnosis of extrapulmonary cancer or interval lung cancer not detected on the baseline scan. Radiologists were not informed of the reason for review and original radiology reports were scored as either "satisfactory", "satisfactory with learning points", or "unsatisfactory". RESULTS: From 6650 participants undergoing LDCT screening, 208 negative scans were reviewed alongside 11 cases with subsequent extrapulmonary cancer and 10 cases with interval lung cancer. Overall, only three reports were ultimately judged "unsatisfactory", 1% of randomly selected negative scans (n = 2/208) and one interval lung cancer scan (n = 1/10). Four out of a total of five cases judged "satisfactory with learning points" were related to oesophageal abnormalities where the participant was subsequently diagnosed with oesophageal cancer. CONCLUSION: The described process attempts to minimise bias in retrospective review of screening scans, and may represent a framework for future QA of national screening programmes. ADVANCES IN KNOWLEDGE: This study describes a structured QA process for a lung cancer screening programme, involving blinded second-read of LDCT screening scans to ensure fair, constructive audit of clinical performance.

Establishing scanning protocols for a CT lung cancer screening trial in the UK.

OBJECTIVES: To develop a CT scanning protocol for lung cancer screening which achieved low radiation dose and a high level of objectively assessed image quality. METHODS: An anthropomorphic chest phantom and a commercially available lung screening image quality phantom were scanned on a series of scan protocols from a previous UK lung screening pilot and on an alternative protocol. The chest phantom scans were used to assess the CT dose metrics on community-based mobile CT scanners and comparisons were made with published recommended doses. Scans of the image quality phantom were objectively assessed against the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) recommendations. Protocol adjustments were made to ensure that the recommended dose and image quality levels were both achieved. RESULTS: The alternative scan protocol yielded doses up to 72% lower than on the previously used protocols with a CTDIvol of 0.6mGy for the 55 kg equivalent phantom and 1.3mGy with an additional 6 cm of tissue equivalent material in place. Scans on the existing protocols failed on two of the QIBA image quality metrics (edge enhancement and 3D resolution aspect ratio). Following adjustments to the reconstruction parameters of the resulting image quality met all six QIBA recommendations. Radiologist review of phantom images with this scan protocol deemed them suitable for a lung screening trial. CONCLUSIONS: Scan protocols yielding low radiation doses and high levels of objectively assessed image quality which meet published criteria can be established through the use of specific anthropomorphic and image quality phantoms, and are deliverable in community-based lung cancer screening. ADVANCES IN KNOWLEDGE: Development of a standard methodology for establishing CT lung screening scanning protocolsUse of QIBA recommendations as objective image quality metricsStandardised lung phantoms are essential tools for setting up lung screening protocols.

A prospective cohort evaluation of the sensitivity and specificity of the chest X-ray for the detection of lung cancer in symptomatic adults.

BACKGROUND: The accuracy of the chest x-ray (CXR) in the identification of lung cancer amongst symptomatic individuals is uncertain. PURPOSE: To determine the diagnostic accuracy of the CXR for the detection of non-small cell carcinomas (NSCLC) and all primary intrathoracic malignancies. METHODS: A prospective cohort study of consecutive CXR reports obtained within a primary care open access initiative. Eligibility criteria were symptoms specified by National Institute for Clinical Excellence as indicative of possible lung cancer and age over 50-yrs. A positive test was a CXR which led directly or indirectly to investigation with CT. The reference standards were malignancies observed within a one- or two-year post-test period. RESULTS: 8,948 CXR outcomes were evaluated. 496 positive studies led to a diagnosis of 101 patients with primary intrathoracic malignancy including 80 with NSCLC. Within two-years, a cumulative total of 168 patients with primary intrathoracic malignancies including 133 NSCLC were observed. The sensitivity and specificity for NSCLC were 76% (95 %CI 68-84) and 95% (95 %CI 95-96) within 1-year and 60% (95 %CI 52-69) and 95% (95 %CI 95-96) within 2-years. The 2-yr positive and negative likelihood ratios were 12.8 and 0.4. The results did not differ for NSCLC compared to all primary malignancies. Within this symptomatic population a negative test reduced the 2-year risk of lung cancer to 0.8%. CONCLUSIONS: A positive test strongly increases the probability of malignancy whereas a negative test does not conclusively exclude the disease. The findings allow the risk of malignancy following a negative test to be estimated.

Long-term nitrofurantoin: an analysis of complication awareness, monitoring, and pulmonary injury cases.

BACKGROUND: Long-term nitrofurantoin (NF) treatment can result in pulmonary and hepatic injury. Current guidelines do not outline the type or frequency of monitoring required for detection of these injuries. AIM: To assess 1) awareness of NF complications among prescribers; 2) monitoring practice; and 3) to describe the pulmonary sequelae of NF-related complications. DESIGN & SETTING: Evaluation of prescribing habits by questionnaires and review of GP databases, and case-note review in secondary care. METHOD: The following study procedures were undertaken: 1) an electronic questionnaire was distributed to prescribers, interrogating prescribing and monitoring practices, and awareness of complications; 2) an analysis was undertaken (June-July 2020) of NF monitoring among GPs in the local clinical commissioning group (CCG); and 3) a case review was carried out of patients diagnosed with NF-induced interstitial lung disease (NFILD) at the interstitial lung disease (ILD) centre (2014-2020). RESULTS: A total of 125 prescribers of long-term NF responded to the questionnaire (82.4% GPs; 12.0% urologists). Many were unaware of the potential for liver (42.4%) and lung (28.0%) complications; 40.8% and 52.8% never monitored for these, respectively. Only 53.3% of urologists believed themselves responsible for arranging monitoring, while nearly all GPs believed this to be the prescriber's responsibility (94.2%). One-third of all responders considered current British National Formulary (BNF) guidelines 'not at all sufficient/clear', with mean clarity scoring of 2.2/5. Among patients with NFILD (n = 46), NF had been prescribed most often (69.6%) for treatment of recurrent UTI and 58.6% (n = 27) were prescribed for >6 months. On withdrawal of the medication 61.4% displayed resolution (completely or minimal fibrosis), while 15.9% of patients had progressive lung fibrosis. CONCLUSION: NF can cause marked or irreversible lung complications and there is currently a shortfall in awareness and monitoring. Existing monitoring guidelines should be augmented.

The not so innocent bystander: an unusual cause of progressive breathlessness.

This case report discusses a 76-year-old man who presented with symptomatic diffuse alveolar-septal and tracheobronchial amyloidosis with a low-grade monoclonal gammopathy. This patient had a combination of both symptomatic diffuse alveolar-septal interstitial disease and tracheobronchial amyloidosis, features that contradict the widely accepted presentations seen in this disease. First, tracheobronchial amyloidosis has been documented as localised disease without systemic involvement. Second, diffuse alveolar-septal interstitial disease is rarely identified with clinical symptoms unless there is significant cardiac involvement. This case highlights a number learning points in the diagnosis and management of systemic amyloid light chain amyloidosis;(1) There is a need for a high index of suspicion for diagnosis due to the potential subtlety of a plasma cell clone underlying AL amyloidosis, requiring serum-free light chain assays to increase sensitivity; (2) Haematological response and recovery of organ dysfunction are not a linear relationship due to the slower reversal of amyloid deposition; therefore, ongoing monitoring is required to identify those in need of repeated therapy. However, haematological response is a marker of overall survival and (3) Multisystem assessment and multidisciplinary collaboration are critical in optimising the care of patients with systemic AL amyloidosis.

Noninvasive Ventilation in Cystic Fibrosis: Clinical Indications and Outcomes in a Large UK Adult Cystic Fibrosis Center.

BACKGROUND: Noninvasive ventilation (NIV) is routinely used to treat patients with cystic fibrosis and respiratory failure. However, evidence on its use is limited, with no data on its role in disease progression and outcomes. The aim of this study was to assess the indications of NIV use and to describe the outcomes associated with NIV in adults with cystic fibrosis in a large adult tertiary center. METHODS: A retrospective analysis of data captured prospectively on the unit electronic patient records was performed. All patients with cystic fibrosis who received NIV over a 10-y period were included in the study. A priori, 2 groups were identified based on length of follow-up, with 2 subgroups identified based on duration of NIV treatment. RESULTS: NIV was initiated on 64 occasions. The duration of follow-up was categorized as > 6 months or < 6 months in 31 (48.4%) and 33 (51.6%) occasions, respectively. The most common indications for starting NIV were chronic (48.5%) and acute (32.8%) hypercapnic respiratory failure. Among those with a follow-up > 6 months, subjects who stopped using NIV early showed a steady median (interquartile range) decline in FEV1 (pre-NIV: -0.04 [-0.35 to 0.03] L/y vs post-NIV: -0.07 [-0.35 to 0.01] L/y, P = .51), while among those who continued using it had an improvement in the rate of decline (pre-NIV: -0.25 [-0.52 to -0.02] L/y vs post-NIV: -0.07 [-0.13 to 0.16] L/y, P = .006). No differences in intravenous antibiotic requirement or pulmonary exacerbations were noted with the use of NIV. Pneumothorax and massive hemoptysis occurred independently in 4 cases. CONCLUSIONS: NIV is being used in cystic fibrosis as adjunct therapy for the management of advanced lung disease in a similar fashion to other chronic respiratory conditions. Adherence to NIV treatment can stabilize lung function but does not reduce pulmonary exacerbations or intravenous antibiotic requirement.

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk.

INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110.

Effect of rituximab or tumour necrosis factor inhibitors on lung infection and survival in rheumatoid arthritis-associated bronchiectasis.

OBJECTIVE: To evaluate rituximab (RTX) in patients with RA-associated bronchiectasis (RA-BR) and compare 5-year respiratory survival between those treated with RTX and TNF inhibitors (TNFi). METHODS: A retrospective observational cohort study of RA-BR in RTX or TNFi-treated RA patients from two UK centres over 10 years. BR was assessed using number of infective exacerbation/year. Respiratory survival was measured from therapy initiation to discontinuation either due to lung exacerbation or lung-related deaths. RESULTS: Of 800 RTX-treated RA patients, 68 had RA-BR (prevalence 8.5%). Post-RTX, new BR was diagnosed in 3/735 patients (incidence 0.4%). At 12 months post-Cycle 1 RTX, 21/68 (31%) patients had fewer exacerbations than the year pre-RTX, 36/68 (53%) remained stable and 11/68 (16%) had increased exacerbations. The rates of exacerbation improved after Cycle 2 and stabilized up to 5 cycles. Of patients who received ≥2 RTX cycles (n = 60), increased exacerbations occurred in 7/60 (12%) and were associated with low IgG, aspergillosis and concurrent alpha-1-antitrypsin deficiency. Overall, 8/68 (11.8%) patients discontinued RTX while 15/46 (32.6%) discontinued TNFi due to respiratory causes. The adjusted 5-year respiratory survival was better in RTX-treated compared with TNFi-treated RA-BR patients; HR 0.40 (95% CI 0.17, 0.96); P =0.041. CONCLUSION: The majority of RTX-treated RA-BR patients had stable/improved pulmonary symptoms in this long-term follow-up. In isolated cases, worsening of exacerbation had definable causes. Rates of discontinuation due to adverse lung outcomes were better for RTX than a matched TNFi cohort. RTX is an acceptable therapeutic choice for RA-BR if a biologic is needed.

Lung cancer stage-shift following a symptom awareness campaign.

BACKGROUND: Lung cancer outcomes in the UK are worse than in many other developed nations. Symptom awareness campaigns aim to diagnose patients at an earlier stage to improve cancer outcomes. METHODS: An early diagnosis campaign for lung cancer commenced in Leeds, UK in 2011 comprising public and primary-care facing components. Rates of community referral for chest X-ray and lung cancer stage (TNM seventh edition) at presentation were collected from 2008 to 2015. Linear trends were assessed by χ2 test for trend in proportions. Headline figures are presented for the 3 years pre-campaign (2008-2010) and the three most recent years for which data are available during the campaign (2013-2015). FINDINGS: Community-ordered chest X-ray rates per year increased from 18 909 in 2008-2010 to 34 194 in 2013-2015 (80.8% increase). A significant stage shift towards earlier stage lung cancer was seen (χ2(1)=32.2, p<0.0001). There was an 8.8 percentage point increase in the proportion of patients diagnosed with stage I/II lung cancer (26.5% pre-campaign vs 35.3% during campaign) and a 9.3% reduction in the absolute number of patients diagnosed with stage III/IV disease (1254 pre-campaign vs 1137 during campaign). INTERPRETATION: This is the largest described lung cancer stage-shift in association with a symptom awareness campaign. A causal link between the campaign and stage-shift cannot be proven but appears plausible. Limitations of the analysis include a lack of contemporary control population.

A prospective study to investigate the role of serial serum mesothelin in monitoring mesothelioma.

BACKGROUND: Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients. METHODS: This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT scans were performed following the completion of chemotherapy, or from baseline in the BSC group. Changes in mesothelin were correlated with radiological progression and overall survival. RESULTS: Forty-one patients with MPM were recruited and followed up for a minimum of 12 months (range 12-21 months). The majority of patients (n = 23) received chemotherapy with pemetrexed and cisplatin. Across the cohort a 10% rise in serum mesothelin could predict radiological progression with a sensitivity of 96% (IQR; 79-100) and specificity of 74% (IQR; 50-91). Sensitivity fell to 80% in sarcomatoid only disease. Patients with a rising mesothelin at 6 months had significantly worse overall survival (175 days) compared to stable/falling levels (448 days) (p = 0.003). CONCLUSIONS: This is the first study to assess serum mesothelin's ability to detect progression of MPM following chemotherapy or during BSC. A 10% rise in serum mesothelin level showed excellent sensitivity at predicting progressive disease. Mesothelin measurement has several advantages over serial CT imaging including reducing hospital visits and cost.

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PURPOSE: The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. PATIENTS AND METHODS: F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. RESULTS: PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. CONCLUSIONS: F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

The physiological consequences of different distributions of diffuse pleural thickening on CT imaging.

OBJECTIVE: Diffuse pleural thickening (DPT) refers to extensive visceral pleural fibrosis with adhesion formation to the parietal pleura obliterating the pleural space. The radiological definition of DPT remains controversial with most of the literature requiring the presence of an obliterated costophrenic angle (CPA) for defining DPT. We conducted a study to investigate the variable distributions of DPT and associated lung function deficit. METHODS: 85 patients referred to a pleural clinic with suspected pleural thickening were screened for our study. Data were collected from 37 patients with DPT confirmed on CT by size criteria (≥3 mm thick, ≥5 cm wide and ≥8 cm in length), and 21 controls with pleural plaques but no other pleuroparenchymal pathology. 27 patients were excluded. Groups were matched to age, body mass index and smoking history. RESULTS: The percentage of predicted forced vital capacity showed a gradual decline from 98.9% for the control group to 83.5% in the DPT without CPA obliteration group (p < 0.05), to 79.5% in the unilateral DPT group (p < 0.001) and 66.7% in the bilateral group (p < 0.001). Similar reductions were seen in the percentage of predicted total lung capacity in the DPT with no CPA obliteration group and the bilateral DPT group. CONCLUSION: Our study shows an incremental reduction in the forced vital capacity and total lung capacity in DPT without CPA obliteration, unilateral and bilateral DPT when compared with a matched control group. Advances in knowledge: Different distributions of DPT including no CPA obliteration can cause respiratory impairment, with bilateral DPT being the worst affected.

Taxonomic review of the genera Micridium Motschulsky, 1869 and Micridina Johnson, 1969 (Coleoptera: Ptiliidae) with eleven new species including the first records from South America and Madagascar.

The six recognised species of the genus Micridium Motschulsky, 1869: M. vittatum (Motschulsky, 1845) M. halidaii (Matthews, 1868), M. angulicolle (Fairmaire, 1858), M. lineatum (Le Conte, 1863). M. rhodeanum (Casey, 1924) and M. groehni Polilov & Perkovsky, 2004 are reviewed and eleven new species: M. attenboroughi sp.n., M. boliviense sp.n., M. elegans sp. n., M. foveatum sp.n., M. inornatum sp.n., M. johnsoni sp.n., M. newtoni sp.n., M. oweni sp.n., M. proprium sp.n., M. quadridens sp.n. and M. thayerae sp.n. are added. The new species are the first records of the genus from South America and Madagascar. The morphological characteristics separating Micridium from other genera in the tribe Ptiliini are discussed and the genus synonymised with the closely related monotypic genus Micridina Johnson, 1969 with its single species M. hilli Johnson, 1969. The synonymy of Dilinium Casey, 1924 with Micridium is confirmed and the type species D. rhodeanum Casey, 1924 re-described. Micridium groehni, described from a single specimen in Baltic amber, does not appear to belong to Micridium as defined here. A key to the new species is provided.

Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years' experience at a single centre.

Objective: To evaluate the effect of rituximab (RTX) in patients with RA-related interstitial lung disease (RA-ILD) and identify factors associated with outcome after treatment. Methods: An observational study of patients with RA-ILD was conducted from a cohort of RTX-treated RA patients in a single centre for >10 years. Progression was defined by any of the following: a decrease of pre-RTX forced vital capacity (FVC) >10% or diffusion capacity of carbon monoxide (DLCO) >15% predicted, worsening of the ILD score or death from progressive ILD. Results: Of 700 RA patients treated with RTX, 56 had RA-ILD (prevalence = 8%). After RTX, new ILD was diagnosed in 3/700 patients (incidence = 0.4%). Data for lung assessment were available for 44/56 patients. The median relative change pre- and post-RTX for FVC were -2.4% and +1.2% ( P = 0.025) and for DLCO were -4.4% and -1.3% ( P = 0.045). Post-RTX, 23/44 (52%) were stable and 7/44 (16%) had improved. Of the 14 (32%) with ILD that progressed, 9/56 (16%) were deaths due to progressive ILD. Factors associated with ILD progression were radiologic pattern of usual interstitial pneumonia, a previous history of lung progression and pre-RTX DLCO <46% predicted. Of those whose ILD progressed, 11/14 (79%) had severe ILD before RTX [median DLCO 42% predicted (interquartile range 41-49)]. Conclusion: In this cohort of patients where RTX was given for arthritis, most patients with ILD pre-RTX remained stable/improved after treatment over a prolonged follow-up period. Patients who deteriorated/died had the most severe ILD pre-RTX, suggesting the drug was not contributory. RTX appears to be an acceptable therapeutic choice for patients with RA-ILD and further studies are warranted.

Novel pyrrolopyrimidines as Mps1/TTK kinase inhibitors for breast cancer.

New targeted therapy approaches for certain subtypes of breast cancer, such as triple-negative breast cancers and other aggressive phenotypes, are desired. High levels of the mitotic checkpoint kinase Mps1/TTK have correlated with high histologic grade in breast cancer, suggesting a potential new therapeutic target for aggressive breast cancers (BC). Novel small molecules targeting Mps1 were designed by computer assisted docking analyses, and several candidate compounds were synthesized. These compounds were evaluated in anti-proliferative assays of a panel of 15 breast cancer cell lines and further examined for their ability to inhibit a variety of Mps1-dependent biological functions. The results indicate that the lead compounds have strong anti-proliferative potential through Mps1/TTK inhibition in both basal and luminal BC cell lines, exhibiting IC50 values ranging from 0.05 to 1.0µM. In addition, the lead compounds 1 and 13 inhibit Mps1 kinase enzymatic activity with IC50 values from 0.356µM to 0.809µM, and inhibited Mps1-associated cellular functions such as centrosome duplication and the spindle checkpoint in triple negative breast cancer cells. The most promising analog, compound 13, significantly decreased tumor growth in nude mice containing Cal-51 triple negative breast cancer cell xenografts. Using drug discovery technologies, computational modeling, medicinal chemistry, cell culture and in vivo assays, novel small molecule Mps1/TTK inhibitors have been identified as potential targeted therapies for breast cancers.

New Species and Records of Costa Rican Featherwing Beetles (Coleoptera:Ptiliidae).

This paper describes a new genus and species of Acrotrichinae, Seminis factiosum gen. n., sp. n.; two new species of Nossidium: Nossidium schuelkei, n. sp. and Nossidium issyae, sp. n.; and  a new species of Ptenidium (Peruvium), Ptenidium gruenbergae  sp. n. from Costa Rica. Three further species: Ptenidium nitidum (Heer),  Petrotrichis rotundata Darby, and Bambara invisibilis Nietner are recorded as being present. With the exception of N. issyae all the insects were collected using a vehicle roof-mounted net on a single 40  kilometre drive from the east and west coasts of the Osa Peninsula by M. Schülke and B. Grünberg in 2012.

Studies of Peruvian Ptiliidae (Coleoptera) 5: Chaska nawi, a new genus and species of Acrotrichinae, Acrotrichini.

Chaska, a new monotypic genus of Acrotrichinae, Acrotrichini with its single species nawi is described and figured. Superficially similar to the more rounded species of Acrotrichis but distinguished by ventral characters in particular the form of the mesoventral collar and the rounded pronotal hind angles. The insect was collected by Dr Caroline Chaboo and her students at the University of Kansas as part of an inventory of leaf beetles in Peru. The name chosen as the winning entry in a national competition to name a beetle species and raise awareness about cryptic biodiversity.

Studies of Peruvian Ptiliidae (Coleoptera) 3: the genus Discheramocephalus Johnson including six new species, and validation of the unavailable generic name Phytotelmatrichis Darby and Chaboo.

Six new species of Discheramocephalus Johnson are described and figured: D. angustus sp. n., D. capac sp. n., D. inretitus sp. n., D. interfusus sp. n., D. malalae sp. n. and D. parvus sp. n.. The insects were collected by Dr Caroline Chaboo and her students at the University of Kansas as part of a programme to compile an inventory of leaf beetles in Peru and are the first records of the genus from the country. A key is provided.                The unavailable genus Phytotelmatrichis Darby & Chaboo is made available from this publication, with Phytotelmatrichis peruviensis Darby & Chaboo 2015 as its type species.