Geographic variation and evolutionary history of Dipodomys nitratoides (Rodentia: Heteromyidae), a species in severe decline

We examined geographic patterns of diversification in the highly impacted San Joaquin kangaroo rat, Dipodomys nitratoides, throughout its range in the San Joaquin Valley and adjacent basins in central California. The currently recognized subspecies were distinct by the original set of mensural and color variables used in their formal diagnoses, although the Fresno kangaroo rat (D. n. exilis) is the most strongly differentiated with sharp steps in character clines relative to the adjacent Tipton (D. n. nitratoides) and short-nosed (D. n. brevinasus) races. The latter two grade more smoothly into one another but still exhibit independent, and different, character clines within themselves. At the molecular level, as delineated by mtDNA cytochrome b sequences, most population samples retain high levels of diversity despite significant retraction in the species range and severe fragmentation of local populations in recent decades due primarily to landscape conversion for agriculture and secondarily to increased urbanization. Haplotype apportionment bears no relationship to morphologically defined subspecies boundaries. Rather, a haplotype network is shallow, most haplotypes are single-step variants, and the time to coalescence is substantially more recent than the time of species split between D. nitratoides and its sister taxon, D. merriami. The biogeographic history of the species within the San Joaquin Valley appears tied to mid-late Pleistocene expansion following significant drying of the valley resulting from the rain shadow produced by uplift of the Central Coastal Ranges

Amygdala responses to fearful and happy facial expressions under conditions of binocular suppression

The human amygdala plays a crucial role in processing affective information conveyed by sensory stimuli. Facial expressions of fear and anger, which both signal potential threat to an observer, result in significant increases in amygdala activity, even when the faces are unattended or presented briefly and masked. It has been suggested that afferent signals from the retina travel to the amygdala via separate cortical and subcortical pathways, with the subcortical pathway underlying unconscious processing. Here we exploited the phenomenon of binocular rivalry to induce complete suppression of affective face stimuli presented to one eye. Twelve participants viewed brief, rivalrous visual displays in which a fearful, happy, or neutral face was presented to one eye while a house was presented simultaneously to the other. We used functional magnetic resonance imaging to study activation in the amygdala and extrastriate visual areas for consciously perceived versus suppressed face and house stimuli. Activation within the fusiform and parahippocampal gyri increased significantly for perceived versus suppressed faces and houses, respectively. Amygdala activation increased bilaterally in response to fearful versus neutral faces, regardless of whether the face was perceived consciously or suppressed because of binocular rivalry. Amygdala activity also increased significantly for happy versus neutral faces, but only when the face was suppressed. This activation pattern suggests that the amygdala has a limited capacity to differentiate between specific facial expressions when it must rely on information received via a subcortical route. We suggest that this limited capacity reflects a tradeoff between specificity and speed of processing

Iterative Segmentation from Limited Training Data: Applications to Congenital Heart Disease

We propose a new iterative segmentation model which can be accurately learned from a small dataset. A common approach is to train a model to directly segment an image, requiring a large collection of manually annotated images to capture the anatomical variability in a cohort. In contrast, we develop a segmentation model that recursively evolves a segmentation in several steps, and implement it as a recurrent neural network. We learn model parameters by optimizing the interme- diate steps of the evolution in addition to the final segmentation. To this end, we train our segmentation propagation model by presenting incom- plete and/or inaccurate input segmentations paired with a recommended next step. Our work aims to alleviate challenges in segmenting heart structures from cardiac MRI for patients with congenital heart disease (CHD), which encompasses a range of morphological deformations and topological changes. We demonstrate the advantages of this approach on a dataset of 20 images from CHD patients, learning a model that accurately segments individual heart chambers and great vessels. Com- pared to direct segmentation, the iterative method yields more accurate segmentation for patients with the most severe CHD malformations.Comment: Presented at the Deep Learning in Medical Image Analysis Workshop, MICCAI 201

Flame Treatment of Polypropylene: A Study by Electron and Ion Spectroscopies

The effects of flame treatment on the surface characteristics of four injection moulded, automotive grade, polypropylene samples, pigmented with carbon black, have been studied. The changes in wettability have been monitored by water contact angle and Dyne inks, whilst XPS has been used to establish the changes in oxygen surface concentration as a function of flame treatment. As expected carbon pigmented and carbon plus talc filled samples showed a significant increase in oxygen concentration and surface wettability with increasing flame treatment. For the glass filled sample this effect was not so pronounced. Inspection of the XPS valence band shows initial attack in the flame treatment process to be at the pendant methyl group of the poly(propylene) molecular architecture. XPS in conjunction with cluster ion bombardment shows the depth of surface treatment to range from ca. 7 nm at one pass of flame treatment to some 15 nm following seven passes. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) shows the segregation of characteristic additives during the injection moulding process which are subsequently greatly reduced during the flame treatment. As treatment level increases oxygen increases from mono-atomic to diatomic attachment. This work extends the understanding of the flame treatment of moulded polyolefines and establishes that the beneficial properties conferred are the result of the conjoint effect of the oxygenation of the bulk polymer along with the removal of surface segregated processing aids

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Evidence for chemokine synergy during neutrophil migration in ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. OBJECTIVES: The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. METHODS: CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. RESULTS: CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. CONCLUSION: This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS

Energy cost and return for hunting in African wild dogs and Cheetahs

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years