Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome.

OBJECTIVE: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren's syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. METHODS: A secure web-based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. RESULTS: A criteria-based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti-SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer's test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. CONCLUSION: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria.

Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development.

STUDY QUESTION: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? SUMMARY ANSWER: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age. WHAT IS KNOWN ALREADY: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. STUDY DESIGN, SIZE, DURATION: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 µg/l: 2.90, 95% CI 1.31-6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P = 0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. LIMITATIONS, REASONS FOR CAUTION: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.

Women's interest in a personal breast cancer risk assessment and lifestyle advice at NHS mammography screening.

Background: Although mortality from breast cancer is declining, incidence continues to increase and is often detected at routine NHS screening. Most middle aged and older women in England attend for screening every 3 years. Assessing their personal breast cancer risk and providing preventative lifestyle advice could help to further reduce breast cancer incidence. Methods: A cross-sectional, self-complete postal survey measured attendees' interest in having a personal risk assessment, expected impact on screening attendance, knowledge of associations between lifestyle and breast cancer and preferred ways of accessing preventative lifestyle advice. Results: A total of 1803/4948 (36.4%) completed questionnaires were returned. Most participants (93.7%) expressed interest in a personal risk assessment and 95% (1713/1803) believed it would make no difference or encourage re-attendance. Two-thirds (1208/1803) associated lifestyle with breast cancer, but many were unaware of specific risks such as weight gain, obesity, alcohol consumption and physical inactivity. NHS sourced advice was expected to be more credible than other sources, and booklets, brief counselling or an interactive website were most preferred for accessing this. Conclusions: Attendees appear to welcome an intervention that would facilitate more proactive clinical and lifestyle prevention and address critical research gaps in breast cancer prevention and early detection.

Role of the dorsolateral prefrontal cortex in context-dependent motor performance.

Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practised a task. Some animal and computer simulation studies have suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC and rTMS Vertex groups. The participants practised three finger sequences associated with a specific incidental context (a coloured circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day 1. The second day testing results showed that the DLPFC group had a significantly lower decrease in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance.

Prenatal paracetamol exposure is associated with shorter anogenital distance in male infants.

STUDY QUESTION: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW? SUMMARY ANSWER: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age. WHAT IS ALREADY KNOWN: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHOD: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants. MAIN RESULTS AND THE ROLE OF CHANCE: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent. LIMITATIONS, REASONS FOR CAUTION: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error. WIDER IMPLICATIONS OF THE FINDINGS: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest.

Invasive candidiasis in liver transplant patients: Incidence and risk factors in a pediatric cohort.

Prolonged OR, re-transplantation, and high-volume intraoperative transfusion have been associated with increased risk for IC in adult LT recipients. Antifungal prophylaxis is recommended for adult patients with these risk factors. There are limited data on the incidence of and risk factors for IC in pediatric LT recipients. A retrospective cohort study of all pediatric LT patients at the CHOP between 2000 and 2012 and the CHP between 2004 and 2012 was performed to define the incidence of IC within 30 days of LT. A 3:1 matched case-control study with incidence density sampling was performed. Conditional logistic regression analyses were used to explore risk factors associated with IC. Among 397 recipients, the incidence of IC was 2.5%. Bivariate analyses showed that ICU admission prior to transplant, OR > 10 h, intraoperative volume infusion of >300 mL/kg, and broad-spectrum antibiotics were significantly associated with IC. In a multivariate model, only ICU admission remained significantly associated with IC. Antifungal prophylaxis was not significantly protective against IC. The low incidence of IC and lack of an identified protective effect from antifungal prophylaxis suggest that prophylaxis in pediatric LT recipients should not be routinely recommended to prevent IC events in the first 30 days post-transplant.

Adopting seven-day working in practice: a report by the Royal College of Physicians and Surgeons of Glasgow.

Following the UK Academy of Medical Royal Colleges Report on seven day consultant present care, the Royal College of Physicians and Surgeons of Glasgow held a symposium to explore clinicians' views on the ways in which clinical care should best be enhanced outside 'normal' working hours. In addition, a survey of members and fellows was undertaken to identify the tests which would make the greatest impact on care out of hours. Key messages were: (a) that seven-day consultant delivered care would not achieve the desired benefit to patient care if introduced in isolation from other inter-relating factors. These include alternatives to hospital admission, enhanced nursing support, increased junior medical, pharmacy, social care and ambulance availability and greater access to selected diagnostic services; (b) that the care of hospital inpatients is a service which is one part of the totality of secondary care provision. Any significant change in the deployment of staff for inpatient care must be carefully managed so as not to result in a reduced quality of care provided by the rest of the system.

Insulin resistance in type 1 diabetes: what is 'double diabetes' and what are the risks?

In this review, we explore the concept of 'double diabetes', a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.

Multidisciplinary assessment of fitness to drive in brain tumour patients in southwestern Ontario: a grey matter.

BACKGROUND: Neurocognitive impairments from brain tumours may interfere with the ability to drive safely. In 9 of 13 Canadian provinces and territories, physicians have a legal obligation to report patients who may be medically unfit to drive. To complicate matters, brain tumour patients are managed by a multidisciplinary team; the physician most responsible to make the report of unfitness is often not apparent. The objective of the present study was to determine the attitudes and reporting practices of physicians caring for these patients. METHODS: A 17-question survey distributed to physicians managing brain tumour patients elicited Respondent demographicsKnowledge about legislative requirementsExperience of reportingBarriers and attitudes to reporting Fisher exact tests were performed to assess differences in responses between family physicians (fps) and specialists. RESULTS: Of 467 physicians sent surveys, 194 responded (42%), among whom 81 (42%) were specialists and 113 (58%) were fps. Compared with the specialists, the fps were significantly less comfortable with reporting, less likely to consider reporting, less likely to have patients inquire about driving, and less likely to discuss driving implications. A lack of tools, concern for the patient-physician relationship, and a desire to preserve patient quality of life were the most commonly cited barriers in determining medical fitness of patients to drive. CONCLUSIONS: Legal requirements to report medically unfit drivers put physicians in the difficult position of balancing patient autonomy and public safety. More comprehensive and definitive guidelines would be helpful in assisting physicians with this public health issue.

Assessing fitness to drive in brain tumour patients: a grey matter of law, ethics, and medicine.

BACKGROUND: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. METHODS: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (mto) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. RESULTS: Of the 158 patients available for analysis, 48 (30%) were reported to the mto, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the mto for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. INTERPRETATION: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue.

A revision of Pheidole Westwood (Hymenoptera: Formicidae) in the islands of the southwest Indian Ocean and designation of a neotype for the invasive Pheidole megacephala.

The myrmicine genus Pheidole Westwood is revised for the smaller islands of the Southwest Indian Ocean: Comoros, Juan de Nova Island, Mauritius, Mayotte, Reunion, and the Seychelles. Descriptions and keys are provided for the thirteen species on these islands of which seven are newly described: P. decepticon sp. n., P. dodo sp. n., P. komori sp. n, P. loki sp. n., P. megatron sp. n., P. ragnax sp. n., P. vulcan sp. n.; and six were previously described: P. braueri Forel, P. fervens Smith, F., P. jonas Forel, P. megacephala (Fabricius), P. parva Forel, and P. teneriffana Forel. New synonymies (with the senior synonym listed first) include P. parva Mayr = P. flavens var. farquharensis Forel, P. parva Mayr = P. tarda Donisthorpe, P. megacephala (Fabricius) = P. picata Forel, P. megacephala (Fabricius) = P. punctulata r. gietleni Forel, 1905, P. megacephala (Fabricius) = P. picata var. bernhardae Emery, 1915, P. megacephala (Fabricius) = P megacephala r. scabrior Forel, and P. teneriffana Forel = P. voeltzkowii Forel. Furthermore, lectotypes are designated from the syntypes of P. braueri, P. fervens, P. jonas, P. parva, and P. teneriffana in order to provide a single name-bearing specimen and to facilitate future taxonomic studies. Finally, a neotype is provided for the untraceable or possibly lost type of the cosmopolitan and invasive P. megacephala, which was originally described by Fabricius from Mauritius (the former 'Ile de France').

Enhancing the Focus: How Does Parental Incarceration Fit into the Overall Picture of Adverse Childhood Experiences (ACEs) and Positive Childhood Experiences (PCEs)?

Despite the five million children in the U.S. with an incarcerated parent, there is limited research on risk and protective factors for this population. We analyzed data from the National Survey for Children's Health (2018) to: (1) examine associations among parental incarceration and other adverse childhood experiences (ACEs), (2) characterize the association between parental incarceration and youth mental health outcomes, (3) examine differences in positive childhood experiences (PCEs; collective socialization, community engagement, neighborhood amenities, and family problem solving) by parental incarceration status, (4) examine whether PCEs were protective against mental health problems and if there was an interaction with parental incarceration status, and (5) examine the interaction between PCEs, parental incarceration, and ACEs on mental health problems. Results revealed that children with incarcerated parents had higher odds of experiencing other ACEs, higher odds of having mental health problems, and experienced fewer PCEs compared to children without incarcerated parents. Further, although PCEs were associated with a lower odds of mental health problems for both children with and without incarcerated parents, they did not mitigate the negative impact of parental incarceration on mental health outcomes. While PCEs attenuated the association between ACEs and mental health, parental incarceration status did not significantly moderate the interaction. These results highlight vulnerabilities and potential protective factors for children with incarcerated parents and have important implications for the development of multilevel intervention strategies that seek to promote resilience and reduce risk for this population.

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

PURPOSE: To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. PATIENTS AND METHODS: Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. RESULTS: There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. CONCLUSION: Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Merging of the National Cancer Institute-funded cooperative oncology group data with an administrative data source to develop a more effective platform for clinical trial analysis and comparative effectiveness research: a report from the Children's Oncology Group.

PURPOSE: The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions. METHODS: COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data. RESULTS: Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described. CONCLUSIONS: These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy.

Global mapping of ecosystem services and conservation priorities.

Global efforts to conserve biodiversity have the potential to deliver economic benefits to people (i.e., "ecosystem services"). However, regions for which conservation benefits both biodiversity and ecosystem services cannot be identified unless ecosystem services can be quantified and valued and their areas of production mapped. Here we review the theory, data, and analyses needed to produce such maps and find that data availability allows us to quantify imperfect global proxies for only four ecosystem services. Using this incomplete set as an illustration, we compare ecosystem service maps with the global distributions of conventional targets for biodiversity conservation. Our preliminary results show that regions selected to maximize biodiversity provide no more ecosystem services than regions chosen randomly. Furthermore, spatial concordance among different services, and between ecosystem services and established conservation priorities, varies widely. Despite this lack of general concordance, "win-win" areas-regions important for both ecosystem services and biodiversity-can be usefully identified, both among ecoregions and at finer scales within them. An ambitious interdisciplinary research effort is needed to move beyond these preliminary and illustrative analyses to fully assess synergies and trade-offs in conserving biodiversity and ecosystem services.

Mapping socio-economic scenarios of land cover change: a GIS method to enable ecosystem service modelling.

We present a GIS method to interpret qualitatively expressed socio-economic scenarios in quantitative map-based terms. (i) We built scenarios using local stakeholders and experts to define how major land cover classes may change under different sets of drivers; (ii) we formalized these as spatially explicit rules, for example agriculture can only occur on certain soil types; (iii) we created a future land cover map which can then be used to model ecosystem services. We illustrate this for carbon storage in the Eastern Arc Mountains of Tanzania using two scenarios: the first based on sustainable development, the second based on 'business as usual' with continued forest-woodland degradation and poor protection of existing forest reserves. Between 2000 and 2025 4% of carbon stocks were lost under the first scenario compared to a loss of 41% of carbon stocks under the second scenario. Quantifying the impacts of differing future scenarios using the method we document here will be important if payments for ecosystem services are to be used to change policy in order to maintain critical ecosystem services.

A pilot study for presence of circulating tumour cells in adenoid cystic carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland neoplasm with a poor long-term prognosis due to multiple recurrences and distant metastatic spread. Circulating tumour cells (CTCs) are tumour cells shed from a primary, recurrent, or metastatic cancer that are detectable in the blood or lymphatics. There is no literature to date confirming the presence of CTCs in ACC. The aim of this study was to determine whether CTCs are detectable in ACC. Blood samples were collected from eight patients with histologically confirmed ACC. The TNM stage of the tumour was recorded, as well as any prior treatment. CTCs were isolated by spiral microfluidics and detected by immunofluorescence staining. Three of the eight patients recruited (32.5%) had staining consistent with the presence of CTCs. Of these three patients with detectable CTCs, one had confirmed pulmonary metastasis, one had suspected pulmonary metastasis and was awaiting confirmation, and one had local recurrence confirmed on re-resection. One patient with known isolated pulmonary metastasis had previously undergone a lung metastasectomy and did not have CTCs detected. CTCs are detectable in ACC. In this small patient sample, CTCs were found to be present in those patients with recurrent local disease and known distant metastatic disease. CTCs in ACC should be investigated further for their potential use as an adjunct in staging, prognosis, and the detection of recurrence.

A phase II study of erlotinib (OSI-774) given in combination with carboplatin in patients with recurrent epithelial ovarian cancer (NCIC CTG IND.149).

OBJECTIVES: Approximately 50% of ovarian cancers have elevated levels of epidermal growth factor receptor (EGFR) which correlates with a poor prognosis. Preclinical evidence suggests that EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib (OSI-774), may potentiate the anti-tumour effects of cytotoxic agents, including carboplatin. Blocking EGFR could thus potentially reverse drug resistance. The primary objective of the study was to assess the response rate to the addition of erlotinib in patients with recurrent ovarian cancer who were receiving carboplatin. METHODS: Patients enrolled on this study had either local or advanced recurrent ovarian cancer with measurable disease. They may have had up to 2 prior chemotherapy regimens, one of which must have contained platinum, and they must have responded to prior platinum therapy. Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule, and carboplatin at an AUC of 5 every 21 days. RESULTS: Fifty patients with recurrent ovarian cancer entered the study, 33 in the platinum-sensitive arm and 17 in the platinum-resistant arm. Of patients evaluable for response, there were 14 partial responses (PR) of 30 evaluable for response (57% objective response rate (ORR)) in the platinum-sensitive arm, and 1 PR of 14 evaluable for response (7% ORR) in the platinum-resistant arm. CONCLUSIONS: The combination of erlotinib and carboplatin was active in patients with platinum-sensitive disease, but not in platinum-resistant disease. The toxicities seen were those expected with carboplatin and erlotinib.

Functional dissociations between subregions of the medial prefrontal cortex on the rodent touchscreen continuous performance test (rCPT) of attention.

Converging evidence in humans, monkeys, and rodents suggests a functional dissociation of cognitive function along the dorso-ventral axis of the prefrontal cortex (PFC). Previous studies of attention suggest that the anterior cingulate cortex (ACC) plays a role in target detection, whereas the prelimbic (PL) cortex is important for tests requiring the combined detection and discrimination of signals. We investigated the effect of discrete, quinolinic acid-induced lesions of subregions of the rat medial PFC (mPFC)-ACC, PL cortex, and infralimbic (IL) cortex-on attentional performance on the recently developed rodent touchscreen continuous performance test (rCPT). Rats were tested under a range of behavioral conditions involving stimulus duration (SD), flanker distraction, temporal predictability, and event rate. Rats with lesions of the PL cortex demonstrated the most persistent attentional impairment under conditions of reduced and variable SD and high event rate (lower discrimination sensitivity [d'] and hit rate), and flanker distraction (lower hit rate). Rats with lesions of the ACC exhibited a profound but transient attentional impairment (lower d' and hit rate) in the early stages of behavioral testing, which ameliorated with repeated testing. Rats with lesions of the IL cortex showed no impairments on response control measures. The PL cortex plays a greater role than the ACC in the detection and discrimination of a complex visual stimulus among multiple nontarget stimuli in the rCPT. The findings support evidence for a functional dissociation of attentional performance along the dorso-ventral axis of the mPFC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).