bluuebunny/crossref_metadata_2025 huggingface dataset:
FALLS FROM BUILDINGS IN THE PAEDIATRIC POPULATION
Authors: Haq H , Fanous R , Clark M , Parikh A
Published: November 2016

Objectives & Background

Approximately 4,000 children under the age of 15 are injured falling from windows in the UK. Ten of the children die and an unknown number suffer serious injuries. This study highlights a number of temporal, demographic and socio-economic risk factors for this mechanism of injury. The study also identifies potential strategies to reduce the number of falls from windows.

Methods

This retrospective study of paediatric patients utilised the Barts Health Trust Paediatric Trauma database. Initially, all patients under 16 years of age, who presented with a fall from a height (window, roof or balcony) between 2010 and 2015 were included. This was followed by a short phone survey that was conducted to find out more about safety measures at the location and housing circumstances.

Results

93 patients presented with falls from a height during the study period. Two (2.15%) of these children died. Boys were twice as likely as girls to fall and 88 (94.6%) were accidents. There was a seasonal pattern with 61% of falls occurring in the summer months. 78 (83.87%) of children with falls from buildings required admission to hospital, with a mean length of stay of 3.37 days. 10.5% of children required admission to the Paediatric Critical Care Unit and 11% required emergency surgery. 53% of patients sustained limb fractures and 42% head injuries. 12% of those patients contacted by telephone survey were experiencing long term health problems. The majority (72.5%) of falls occurred in neighbourhoods ranked within the 30% most deprived in the country. Only 12% of the households represented in this study had functioning safety locks. 12% of those children who fell from windows had a pre-existing diagnosis of autism.

Conclusion

This study quantifies the impact the falling from windows had on individual children, their families and the broader healthcare system. This study also suggest that window locks are extremely effective at reducing falls and should be evaluated as a public health intervention. Furthermore, the disproportionately high number of autistic child that falls from windows should prompt an urgent review to ensure these vulnerable children are living in a safe environment.
USING IN SITU SIMULATION TO GET PAEDIATRIC CODE RED RIGHT
Authors: Anpananthar A , Parikh A , Galea J
Published: November 2016

Objectives & Background

A paediatric code red (massive haemorrhage) call is rare but when it does happen, it needs to be performed correctly. In our major trauma centre, our adult emergency department (ED) teams have regular code red calls and have thus fine-tuned the process. We used a series of in-situ high-fidelity simulation to improve how we practically managed a paediatric code red in our ED.

Methods

A paediatric code red trauma scenario was delivered using high-fidelity simulation. 3 sessions were delivered over 9 months in our paediatric ED with immediate debriefing of the team and observers.

Results

There were >20 members of the multidisciplinary team (MDT) at each session. The key concerns identified from debriefing were acted upon. These included.

▸ Communication: problems in the bleep system were identified. One key change is that the radiology registrar now holds a bleep to attend these calls. There is poor network coverage in the hospital for mobile phones and there is now an on-going discussion about the need for more portable phones. The team members on the switchboard list were identified and amended to be specific for a paediatric call.

▸ Team work: aide memoires with key tasks for each of the paediatric trauma team member were adapted from the adult cards

▸ Equipment: a mobile paediatric code red trolley was commissioned by the anaesthetic team to address the repeated questions about which trauma lines were available for younger children.

▸ Training: gaps in knowledge for the MDT were acted upon, including increased frequency of Belmont training for the paediatric nurses. The general paediatric doctors now have a trauma specific workshop to understand their roles and trauma terminology included in their regular teaching program.

▸ Major issues were reported via our DATIX system which helped efficiently deliver on some of the changes. Action and learning points were communicated with the leads for all the relevant departments via email. Debriefing sessions also gave the MDT an opportunity to identify different members of the team and open doors for other discussions.

Conclusion

The simulation and debriefing sessions were key to identifying gaps and in improving the process of managing a paediatric code red by our trauma teams. We worked successfully with our simulation department and these sessions have been set up to continue running to ensure all new teams will benefit from managing this rare event and to continue to fine-tune the process.
WHO ARE OUR ‘CODE-RED’ KIDS? – A URBAN MAJOR TRAUMA CENTRE'S EXPERIENCE OF MAJOR HAEMORRHAGE IN INJURED CHILDREN
Authors: Randhawa H , Edwards MA , Cantle F
Published: November 2016

Objectives & Background

Major trauma in children, while being relatively uncommon, is still a principal cause of preventable death with severe haemorrhage being one of the main responsible reasons. ‘Major haemorrhage protocols’ (known in our institution as a ‘Code Red’) have been widely introduced in order to make large amounts of blood products available quickly. Most protocols, including the 'Code Red' involve adaptations for paediatrics. The ratio of blood products is 1:1 packed red blood cells (PRBCs) to Fresh Frozen Plasma (FFP) mirroring the adult literature that has evidence of improved outcomes.

The objective was to investigate the incidence, demographics, physiology and outcomes of the children triggering a ‘Code Red’ protocol.

Methods

All ‘code red’ activations for children (all those ≤18 years) from 1st Jan 2010 to 31st Dec 2015 were identified then resuscitation room records and computer databases were scrutinised.

Results

1104 children presented during this period as 'trauma call' pre-alerts with only 36 children triggered the ‘Code Red’ protocol (3%). 31 actually received blood with 5 receiving products from prehospital teams.

The age distribution was unsurprisingly skewed towards older age groups (median 17 years, mean 15.4 years) and predominantly male 89%. Only 3 cases were under 12.

28 (78%) had penetrating trauma of which 4 were gun shot wounds.

4 arrived in traumatic cardiac arrest (100% mortality) and were given the most blood products. Of the other patients, only 25% were hypotensive and only 47% were tachycardic.

Low haemoglobin, deranged clotting or both were seen in 27 cases, with worsening coagulation in 13 patients post transfusion.

5 children (18%) of patients receiving more than one unit of PRBCs, had a 1:1* ratio of PRBC:FFP. *(permitted to be a difference of 1 unit only)

25 cases were taken direct to theatre with an overall mortality of 25%, with 2 deaths in the emergency department, 4 in theatre and 3 later in critical care.

Conclusion

The most common paediatric case to trigger a major haemorrhage protocol at our intitution (72%) is a teenage male with penetrating trauma. 'Code Red' calls for smaller children or those sustaining blunt trauma are extremely rare.

The data supports the caution that vital signs are poor indicators of hypovolaemia and, despite the protocols, it is still difficult to ensure recommended ratios of blood to plasma are administered.
A PRE-HOSPITAL ANALYSIS OF PAEDIATRIC MAJOR TRAUMA IN THE GREATER DUBLIN AREA
Authors: Kelly O , O'Reilly M , Collins NC
Published: November 2016

Objectives & Background

The provision of both Paediatric and Trauma care in Ireland is undergoing reconfiguration with the formation of a National Children's Hospital (NCH) and Major Trauma Centres and Networks. This will result in the amalgamation of three paediatric emergency departments (EDs) in Dublin into one centralised ED and two satellite centres.

Ambulance care in the Greater Dublin Area is provided by Dublin Fire Brigade (DFB) and the National Ambulance Service (NAS).

Central to service design and provision is an understanding of demand and patient centred factors. This study aims to study the burden of major paediatric trauma in the Greater Dublin Area as served by DFB in order to inform policy and strategic healthcare planning.

Methods

Data from DFB was analysed to determine the incidence of major paediatric trauma in the Dublin area in 2014. ‘Major Trauma’ was defined as a trauma where the attending paramedics placed the receiving ED on ‘standby’. The incident locations were mapped using Central Statistics Office small areas. Data was analysed to determine the median travel time and range to the receiving ED and the proposed NCH, diurnal variation, and the mechanism of injury.

Results

DFB responded to 58 paediatric Major Traumas in 2014. Paediatric trauma was focused in suburban areas (Image 1).

The median (range) travel time to the current 3 hospitals was 10 mins 15 secs (2'38”–32'12”), this was estimated to change to 18 mins (6'–35') with the opening of a single NCH.

12% of cases occurred between the night time hours of 22:00–07:30.

Burns equated for the majority (34.5%) of the incidents, with traffic accidents and falls both accounting for 20.7% (Image 2).

Conclusion

The low incidence of paediatric Major Trauma documented in the Greater Dublin Area may reflect the lack of both NAS data and predetermined hospital pre-alert criteria for Major Trauma.

Information pertaining to location and timing is vital to hospital staffing procedures and specialty service provision, allowing strategic planning according to likely demand. An awareness of the mechanism of injury of paediatric patients can guide the need for specialist services.

The change from the current paediatric service to that of one centralised ED would result in an estimated median increase of 7.75 mins in transit time.

It is envisaged that this data can in strategic planning of healthcare provision, particularly at this pivotal moment of reconfiguration in Ireland.

Figure 1

Figure 2
NON-ACCIDENTAL INJURY: AN IMPORTANT CAUSE OF PAEDIATRIC MAJOR TRAUMA
Authors: Parry N , Goldsworthy L , Melsom S , Fryer J , Haythornthwaite G
Published: November 2016

Objectives & Background

To establish the number of major trauma patients attending Bristol Royal Hospital for Children's Emergency Department with child protection concerns and suspected non- accidental injury (NAI). To identify the difference in injury patterns of children with suspected NAI versus accidentally injured children. NAI is an important cause of paediatric major trauma. There is a lack of research on NAI as a cause for paediatric major trauma. Results from national Trauma Audit & Research Network (TARN) data suggest that children with NAI have increased Injury Severity (ISS) and a higher mortality rate. According to TARN data in 2012, 10.1% of children with major trauma were <2 years old with NAI.

Methods

All paediatric major trauma patients from 27/04/14- 26/12/14 were included. Electronic case-notes were reviewed. Information collected included: Injury Severity Score; mechanism of injury; injuries sustained; child protection documentation; imaging; disposal and outcome.

Results

122 Paediatric major trauma patients presented to ED and were included. 40 patients were secondary transfers. There was a weak positively skewed relationship between age and ISS. Mechanisms of injury were diverse. Commonest accidental injuries sustained were head, limb and abdominal/pelvic injuries. Child protection concerns were raised in 31 of the cases. 13 of these children had suspected NAI. Of these, there were 9 isolated injuries that included: 7 head injuries, 1 rectal perforation and 1 perineal tear. The remainder of cases involved severe multi-system trauma: 2 head injuries, 1 abdominal injury, 2 limb injuries, 3 chest injuries and 1 spinal injury. Non-ambulant children underwent the greatest proportion of CT heads compared to older children. 7/9 children in the suspected NAI group with head injuries were under 1-year-old. 9% all children were <2 years old with suspected NAI. Community Paediatricians were involved all suspected NAI cases.

Conclusion

The findings of this study support previous TARN data, which suggests that NAI is a common cause of major trauma. Injury patterns are different in this group compared to accidental injury with increased proportion of head injuries, especially amongst the non-ambulant children.

Figure 1

Figure 2

Figure 3

Figure 4
Abstracts from international Emergency Medicine journals
Authors: Weber Ellen J
Published: November 2016

Editor's note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors.
Whole-genome profiling helps to classify phyllodes tumours of the breast
Authors: Laé Marick , La Rosa Philippe , Mandel Jonas , Reyal Fabien , Hupé Philippe , Terrier Philippe , Couturier Jérôme
Published: November 2016

Aims

The aim of this study was to analyse a series of borderline and malignant phyllodes tumours (PTs) of the breast by whole-genome profiling to identify genomic markers that could help to recognise potentially malignant tumours within borderline tumours.

Methods

We evaluated the genetic imbalances of a series of 53 PTs (30 borderline, 23 malignant) using the Human CNV370 BeadChip microarray (Illumina), containing 370 000 SNP markers and correlate this alterations with clinicopathological features.

Results

Forty-five PTs (85%) showed chromosome copy number variations (CNVs). Twenty PTs (37%) showed five or more chromosomal imbalances (8/30 borderline (27%) and 12/23 malignant (52%)). The large-scale genetic changes associated with malignant were+7p (9/23), +1q (8/23), −10p (8/23), −13q14 (7/23), +8q (6/23) and +10q (6/23) and borderline were+1q (13/30), −13q14 (9/30), −6q (8/30) and −10p (8/30). Losses in 9p21.3, encompassingCDKN2A/Bgene, were present in three tumours (malignant), whereas deletions of 13q, with a minimal region in 13q14.2 encompassing theRB1gene, were found in 9/30 borderline and 7/28 malignant tumours. High-level amplifications were seen in eight tumours (seven malignant and one borderline): in 7p in three tumours (includingEGFRin two), 7q31.2 (includingTFECandMET), 8q24.21 (includingMYC) and 8q23.3 (includingCSMD3) in one tumour each.

Conclusions

Whole-genome profiling by SNP arrays in PTs leads to identify a high number of CNV, gains of 7p and 8q, losses of 13q and 10, losses in 9p21.3 (CDKN2A/B) and the presence of amplifications, especially involvingEGFR, as markers of potentially malignant tumours.
Is a detailed grading of villous atrophy necessary for the diagnosis of enteropathy?
Authors: Biagi Federico , Vattiato Claudia , Burrone Marco , Schiepatti Annalisa , Agazzi Simona , Maiorano Gregorio , Luinetti Ombretta , Alvisi Costanza , Klersy Catherine , Corazza Gino Roberto
Published: November 2016

Aims

The utility of the 7 level Marsh–Oberhuber classification of mucosal damage in patients with coeliac disease has recently been criticised. Analysis of duodenal biopsies with dissecting microscopy is an unsophisticated method that, however, provides useful information in cases of frank villous atrophy. In the last 15 years, we have always analysed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. If the results of dissecting microscopy and traditional histology were comparable, we feel that would be strong evidence that grading of the histological lesion would be unnecessary if not pointless in the everyday diagnosis of enteropathies.

Methods

The clinical notes of all 2075 patients undergoing duodenal biopsy between September 1999 and June 2015 were retrospectively analysed. Results of duodenal mucosal evaluation with both dissecting microscopy and traditional histology were collected and statistically compared.

Results

The κ statistics showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%).

Conclusions

Although dissecting microscopy is an unsophisticated method that obviously cannot substitute traditional histology, our results suggest that in everyday clinical practice, the diagnosis of coeliac disease and other flat enteropathies does not require grading of villous atrophy.
A simple human co-culture model of lymphatic invasion
Authors: Naidoo Kalnisha
Published: November 2016

True lymphovascular invasion in most carcinomas adversely affects survival, butin vitrohuman models of lymphatic invasion are lacking. Herein is discussed one such model in which certain mechanistic aspects of lymphatic dissemination can be investigated easily in any laboratory. S100P expression is known to be significantly upregulated in the lymph node metastases of human pancreatic adenocarcinoma. Thus, an S100P overexpressing cell line (S5L) and a vector control (V3L) pancreatic cancer cell lines were used to develop a co-culture model with human dermal lymphatic endothelial cells. Adhesion, the effect of cancer cells on lymphatic permeability and trans-lymphatic endothelial migration could be reproducibly quantified in this model and parametric statistical analysis confirmed significant differences between the two cancer cell lines in these functional assays. This proof-of-principle study demonstrates that this simple model can be used to assess lymphatic invasion in a human cancer context in real-time in vitro.
The subjective cut: sex reassignment surgery in 1960s and 1970s science fiction
Authors: Sellberg Karin
Published: November 2016

This article considers the way in which ethical concerns about sex reassignment surgery and especially the research and clinical practice of the sexologist Dr John Money (1921–2006) is being negotiated in the 1960s and 1970s novelsMyra BreckinridgeandMyronby Gore Vidal andThe Passion of New Eveby Angela Carter. Drawing on the theories of gender and embodiment developed by Money, the article reads the novels as a critical response and discursive interaction with emergent sexological concepts.
Flat-detector computed tomography PBV map in the evaluation of presurgical embolization for hypervascular brain tumors
Authors: Wen Li-Li , Zhang Xin , Zhang Qing-Rong , Wu Qi , Chen Shu-Juan , Deng Jin-Long , Huang Kaiyi , Wang Han-Dong
Published: November 2016

Background

Preoperative embolization of hypervascular brain tumors is frequently used to minimize intraoperative bleeding.

Objective

To explore the efficacy of embolization using flat-detector CT (FDCT) parenchymal blood volume (PBV) maps before and after the intervention.

Materials and methods

Twenty-five patients with hypervascular brain tumors prospectively received pre- and postprocedural FDCT PBV scans using a biplane system under a protocol approved by the institutional research ethics committee. Semiquantitative analysis, based on region of interest measurements of the pre- and post-embolization PBV maps, operating time, and blood loss, was performed to assess the feasibility of PBV maps in detecting the perfusion deficit and to evaluate the efficacy of embolization.

Results

Preoperative embolization was successful in 18 patients. The relative PBV decreased significantly from 3.98±1.41 before embolization to 2.10±2.00 after embolization. Seventeen patients underwent surgical removal of tumors 24 hours after embolization. The post-embolic tumor perfusion index correlated significantly with blood loss (ρ=0.55) and operating time (ρ=0.60).

Conclusions

FDCT PBV mapping is a useful method for evaluating the perfusion of hypervascular brain tumors and the efficacy of embolization. It can be used as a supplement to CT perfusion, MRI, and DSA in the evaluation of tumor embolization.
The Barrel stent: new treatment option for stent-assisted coiling of wide-necked bifurcation aneurysms—results of a single-center study
Authors: Mühl-Benninghaus Ruben , Simgen Andreas , Reith Wolfgang , Yilmaz Umut
Published: November 2016

Purpose

The Barrel stent is a laser cut stent designed for stent-assisted coil embolization of wide-necked bifurcation or branch aneurysms with a single device, with the purpose of lowering the metal-to-artery ratio and its inherent risk of thromboembolic complications of multiple stents. We report our early experiences with this device in 17 patients in this retrospective single-center analysis.

Materials and methods

17 consecutive patients who underwent stent-assisted coil embolization of wide-necked bifurcation aneurysms with the Barrel stent were retrospectively identified. We analyzed the feasibility of successful deployment and post-treatment angiographic results. Adverse events, clinical outcome, and angiographic follow-up results were also analyzed.

Results

Aneurysms were located in the internal carotid artery (n=3), the middle cerebral artery (n=9), the anterior communicating artery (n=3), and the basilar artery (n=2). In the immediate post-treatment angiography, adequate occlusion (neck remnant or total occlusion) was observed in 16/17 (94.1%) of aneurysms. One patient experienced a transient ischemic attack. No permanent neurologic deficits were observed. 13/17 (76.5%) patients underwent short-term follow-up angiography after 3 months, all of which showed adequate occlusion of the aneurysm.

Conclusions

In this small retrospective single-center analysis we show that stent-assisted coiling with the Barrel stent is a safe and effective option for the endovascular treatment of intracranial wide-necked bifurcation aneurysms.
Massive open online courses (MOOCs) as a window into the veterinary profession
Authors: Paterson J. , Hughes K. , Steer L. , Das Gupta M. , Boyd S. , Bell C. , Rhind S.
Published: November 2016

Massive open online courses (MOOCs) are freely available online courses open to anyone who registers and typically are associated with thousands or hundreds of thousands of participants. Using an established online platform, the authors created and delivered a five‐week MOOC aimed primarily at prospective veterinary students, but open to anyone with an interest in finding out more about the veterinary profession in general. 11,911 people signed up for the course, and of these, 8137 interacted in some way with the course and 1716 received a certificate of completion. The majority of participants (84 per cent) were female, and there was a wide age range (under 18 to over 65). Most participants were from North America or the UK. 65 per cent of those completing the entry survey were hoping or intending to work in the vet profession in the future, while 33 per cent were not. Qualitative data indicated that the course was helpful in aiding those undecided as to whether they wanted to be a veterinarian or not to decide one way or another whether they want to pursue veterinary medicine as a career. Furthermore, the course was seen as being a useful introduction to the veterinary profession even for those who had no intention of working in the field.
Apoptosis of rat hepatic stellate cells induced by diallyl trisulfide and proteomics profiling in vitro
Authors: Zhang Yajie , Zhou Xiaoming , Xu Lipeng , Wang Lulu , Liu Jinling , Ye Jing , Qiu Pengxin , Liu Qinghua
Published: November 2016

Diallyl trisulfide (DATS), a major garlic derivative, inhibits cell proliferation and triggers apoptosis in a variety of cancer cell lines. However, the effects of DATS on hepatic stellate cells (HSCs) remain unknown. The aim of this study was to analyze the effects of DATS on cell proliferation and apoptosis, as well as the protein expression profile in rat HSCs. Rat HSCs were treated with or without 12 and 24 μg/mL DATS for various time intervals. Cell proliferation and apoptosis were determined using tetrazolium dye (MTT) colorimetric assay, bromodeoxyuridine (5-bromo-2′-deoxyuridine; BrdU) assay, Hoechst 33342 staining, electroscopy, and flow cytometry. Protein expression patterns in HSCs were systematically studied using 2-dimensional electrophoresis and mass spectrometry. DATS inhibited cell proliferation and induced apoptosis of HSCs in a time-dependent manner. We observed clear morphological changes in apoptotic HSCs and dramatically increased annexin V-positive – propidium iodide negative apoptosis compared with the untreated control group. Twenty-one significant differentially expressed proteins, including 9 downregulated proteins and 12 upregulated proteins, were identified after DATS administration, and most of them were involved in apoptosis. Our results suggest that DATS is an inducer of apoptosis in HSCs, and several key proteins may be involved in the molecular mechanism of apoptosis induced by DATS.
再思零散工婦女的就業風險與應對策略
Authors: 陳 鳳儀 , 曾 玉蘭
Published: November 2016

在婦女與就業的討論上，主流社會工作對女性的理解，均以家庭照顧者、家長或母親角色為主，可以說女性在工作場境中的身份是隱性的，且較以「受助人」身份或受制於家庭經濟策略來理解女性參與工作。一些以女性作為「服務參與者」的討論，也多環繞其「義工」身份，這種取向自然較少討論女性就業保障議題，更重要的是沒有處理女性在面對「風險社會」(risk society)的挑戰時，如何在工作場境爭取「自主性」，以致追尋實現「自我」。因此，突顯女性在工作意義上的探討，正能補充主流社會工作討論的欠缺。就著這種研究取向，我們在二零一二年完成了一項「再思零散工婦女的就業風險與應對策略」報告，記錄了十五位零散工婦女的深入訪談。本文集中探討她們對工作的體會與選擇，目的是透過理解零散工婦女的個人經歷與就業風險，讓我們重新思考「工作」對女性的獨特含義。
Infiltration in two types of embankments and the effects of rainfall time on the stability of slopes
Authors: Tu Guoxiang , Huang Runqiu
Published: November 2016

We have studied discrepancies between rainfall infiltration and the effects of rainfall time on slope stability using two expressway embankments consisting of soil with different permeability as examples to monitor variations in water content and porewater pressure of the embankments during two typical rainfall events. The results were as follows. (1) Rainfall infiltration in the sandy clay embankment occurred in three phases: complete infiltration, rate-reducing infiltration and stable infiltration. Rainfall infiltration in the gravel embankment could be divided into two phases: complete infiltration and water table rise. The wetting front in the sandy clay embankment moved down slowly with time, and the volumetric moisture content between the infiltration surface and wetting front ranged from 20 to 42% and decreased with depth. In the gravel embankment, the wetting front dropped rapidly, and the soil volumetric moisture content between the infiltration surface and wetting front remained within a low range of 2.8 – 3.5% during the rainfall event. (2) During the rainfall event, the variation of porewater pressure in the sandy clay embankment lagged behind rainfall and was affected mostly by the wetting front moving down. In contrast, in the gravel embankment porewater pressure variation did not lag far behind rainfall. (3) The effect of infiltration on slope stability was greater for the gravel embankment than for the sandy clay embankment. The factor of safety for the former decreased rapidly during the rainfall events and recovered with almost no delay after the rainfall event ended, whereas the factor of safety for the latter decreased slowly and continued to decrease for 2 – 9 days after the rainfall event ended. (4) If the total rainfall was constant, for the sandy clay embankment the effect of rain intensity on the factor of safety of the slope was smaller than that for the gravel embankment, and the factor of safety for the sandy clay embankment was controlled by the rainfall intensity and duration.
Performance of the reinforced right abutment slope of Zipingpu Dam during magnitude 8.0 earthquake, Wenchuan, China
Authors: Ren Aiwu , Wang Yujie , Chen Zuyu , Song Yangang , Sun Ping
Published: November 2016

On 12 May 2008, an earthquake of magnitude 8.0 on the Richter scale occurred at Wenchuan in China. Zipingpu dam also experienced the earthquake. The maximum ground acceleration near the top of the 156 m high rockfill dam exceeded 2 
g
. The right dam abutment slope, which accommodates all the discharge facilities, remained intact after this severe earthquake. However, the natural slopes on the opposite side of the reservoir were severely damaged. It has been found that the reinforcement provided by more than 1000 prestressed cables in the right abutment slope helped to stabilize it. Measurements from multipoint extensometers and load cells installed in the slope showed that there were sudden changes in displacement and stress during the earthquake. This is clear evidence that reinforcement with anchored cables can be successfully used to stabilize a slope.
File Dissemination in Dynamic Graphs
Authors: Nain Philippe , Towsley Don
Published: November 2016

In this article, we investigate the traversal time of a file across
N
communication links subject to stochastic changes in the sending rate of each link. Each link’s sending rate is modeled by a finite-state Markov process. Two cases, one where links evolve independently of one another (
N
mutually independent Markov processes) and the second where their behaviors are dependent (these
N
Markov processes are not mutually independent), are considered. A particular instance where the above is encountered is ad hoc delay/tolerant networks where links are subject to intermittent unavailability.
Generalized Deep Transfer Networks for Knowledge Propagation in Heterogeneous Domains
Authors: Tang Jinhui , Shu Xiangbo , Li Zechao , Qi Guo-Jun , Wang Jingdong
Published: November 2016

In recent years, deep neural networks have been successfully applied to model visual concepts and have achieved competitive performance on many tasks. Despite their impressive performance, traditional deep networks are subjected to the decayed performance under the condition of lacking sufficient training data. This problem becomes extremely severe for deep networks trained on a very small dataset, making them overfitting by capturing nonessential or noisy information in the training set. Toward this end, we propose a novel generalized deep transfer networks (DTNs), capable of transferring label information across heterogeneous domains, textual domain to visual domain. The proposed framework has the ability to adequately mitigate the problem of insufficient training images by bringing in rich labels from the textual domain. Specifically, to share the labels between two domains, we build parameter- and representation-shared layers. They are able to generate domain-specific and shared interdomain features, making this architecture flexible and powerful in capturing complex information from different domains jointly. To evaluate the proposed method, we release a new dataset extended from NUS-WIDE at http://imag.njust.edu.cn/NUS-WIDE-128.html. Experimental results on this dataset show the superior performance of the proposed DTNs compared to existing state-of-the-art methods.
Biomarkers in Veterinary Medicine
Authors: Myers Michael J. , Smith Emily R. , Turfle Phillip G.
Published: November 2016

This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.
Firmly Planted, Always Moving
Authors: Raikhel Natasha V.
Published: November 2016

I was a budding pianist immersed in music in Leningrad, in the Soviet Union (now Saint Petersburg, Russia), when I started over, giving up sheet music for the study of ciliates. In a second starting-over story, I emigrated to the United States, where I switched to studying carbohydrate-binding plant lectin proteins, dissecting plant vesicular trafficking, and isolating novel glycosyltransferases responsible for making cell wall polysaccharides. I track my journey as a plant biologist from student to principal investigator to founding director of the Center for Plant Cell Biology and then director of the Institute for Integrative Genome Biology at the University of California, Riverside. I discuss implementing a new vision as the first and (so far) only female editor in chief of Plant Physiology, as well as how my laboratory helped develop chemical genomics tools to study the functions of essential plant proteins. Always wanting to give back what I received, I discuss my present efforts to develop female scientist leadership in Chinese universities and a constant theme throughout my life: a love of art and travel.
Apoptosis and Cancer
Authors: Letai Anthony
Published: November 2016

Cancer is a disease involving the abnormal accumulation of cells resulting from an imbalance of proliferation and programmed cell death. This review focuses on the mitochondrial apoptotic pathway, a mechanism of programmed cell death with particular relevance to cancer. Starting over 30 years ago, basic findings in model organisms have been combined with findings in clinical cytogenetics to uncover a family of proteins, the BCL-2 family, that regulates the commitment to apoptosis by controlling permeabilization of the mitochondrial outer membrane. Cancer cells are generally more poised to engage the apoptotic machinery than normal cells are, a fact that likely underlies much of the therapeutic index exploited by many types of cancer chemotherapy. More recently, small molecules directly targeting the antiapoptotic proteins of the BCL-2 family have entered the clinic for testing in cancer. One therapeutic, venetoclax (ABT-199), has recently gained FDA approval in a landmark achievement for the apoptosis community. Important future efforts will be directed at building combinations of agents that selectively induce apoptosis in cancer cells.
The Ambrosia Symbiosis: From Evolutionary Ecology to Practical Management
Authors: Hulcr Jiri , Stelinski Lukasz L.
Published: November 2016

The ambrosia beetle–fungus farming symbiosis is more heterogeneous than previously thought. There is not one but many ambrosia symbioses. Beetle-fungus specificity is clade dependent and ranges from strict to promiscuous. Each new origin has evolved a new mycangium. The most common relationship with host trees is colonization of freshly dead tissues, but there are also parasites of living trees, vectors of pathogenic fungi, and beetles living in rotten trees with a wood-decay symbiont. Most of these strategies are driven by fungal metabolism whereas beetle ecology is evolutionarily more flexible. The ambrosia lifestyle facilitated a radiation of social strategies, from fungus thieves to eusocial species to communities assembled by attraction to fungal scent. Although over 95% of the symbiotic pairs are economically harmless, there are also three types of pest damage: tree pathogen inoculation, mass accumulation on susceptible hosts, and structural damage. Beetles able to colonize live tree tissues are most likely to become invasive pests.
Acquisition of Quantifiers
Authors: Crain Stephen
Published: November 2016

Explaining children's nonadult interpretations of sentences with quantifiers has been the objective of extensive research for more than 50 years. This article reviews four areas of research, each of which began with the observation that children and adults respond differently to sentences with quantifiers. The observed differences have been subject to considerable debate, often drawing upon linguistic theory for answers and sometimes resulting in changes to the theory. This article begins by discussing children's comprehension of sentences with pronouns with quantificational versus referential antecedents. The next topic is children's nonadult responses to sentences with quantifiers and negation. The third topic is children's analysis of scope phenomena. I conclude with a discussion of children's understanding of the focus adverb only, which is used to expose some common properties of historically distinct languages. Progress in each of these four areas has revealed children's deep understanding of the basic meanings of quantifiers and how quantifiers interact with other logical expressions. I conclude that children's nonadult interpretations of quantifiers are consistent with the theory of Universal Grammar.
CAR T Cell Therapy for Solid Tumors
Authors: Newick Kheng , O'Brien Shaun , Moon Edmund , Albelda Steven M.
Published: November 2016

The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematologic malignancies (e.g., CD19 CARs in leukemias). However, this success has yet to be extrapolated to solid tumors, and the reasons for this are being actively investigated. We characterize some of the challenges that CAR T cells have to surmount in the solid tumor microenvironment and new approaches that are being considered to overcome these hurdles.
Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies
Authors: Lesnefsky Edward J. , Chen Qun , Tandler Bernard , Hoppel Charles L.
Published: November 2016

Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury. The new concept that mitochondria are not merely stochastic sites of oxidative and calcium-mediated injury but that they activate cellular responses of mitochondrial remodeling and cellular reactions that modulate the balance between cell death and recovery is reviewed, and the therapeutic implications of this concept are discussed.
A Critical and Comparative Review of Fluorescent Tools for Live-Cell Imaging
Authors: Specht Elizabeth A. , Braselmann Esther , Palmer Amy E.
Published: November 2016

Fluorescent tools have revolutionized our ability to probe biological dynamics, particularly at the cellular level. Fluorescent sensors have been developed on several platforms, utilizing either small-molecule dyes or fluorescent proteins, to monitor proteins, RNA, DNA, small molecules, and even cellular properties, such as pH and membrane potential. We briefly summarize the impressive history of tool development for these various applications and then discuss the most recent noteworthy developments in more detail. Particular emphasis is placed on tools suitable for single-cell analysis and especially live-cell imaging applications. Finally, we discuss prominent areas of need in future fluorescent tool development—specifically, advancing our capability to analyze and integrate the plethora of high-content data generated by fluorescence imaging.
Knockdown of PTRF ameliorates adipocyte differentiation and functionality of human mesenchymal stem cells
Authors: Perez-Diaz Sergio , Garcia-Rodriguez Beatriz , Gonzalez-Irazabal Yolanda , Valero Monica , Lagos-Lizan Javier , Arbones-Mainar Jose M.
Published: November 2016

Healthy expansion of human adipose tissue requires mesenchymal stem cells (hMSC) able to proliferate and differentiate into mature adipocytes. Hence, characterization of those factors that coordinate hMSC-to-adipocyte transition is of paramount importance to modulate the adipose tissue expansion. It has been previously reported that the adipogenic program of hMSC can be disrupted by upregulating caveolar proteins, and polymerase I and transcript release factor (PTRF) is an integral component of caveolae, highly expressed in adipose tissue. Here, we hypothesized that the role of PTRF in adipocyte functionality might stem from an effect on hMSC. To test this hypothesis, we isolated hMSC from the subcutaneous fat depot. We found an upregulated expression of the PTRF associated with decreased adipogenic potential of hMSC, likely due to the existence of senescent adipocyte precursors. Employing short hairpin RNA-based constructs to stably reduce PTRF, we were able to restore insulin sensitivity and reduced basal lipolysis and leptin levels in human adipocytes with high levels of PTRF. Additionally, we pinpointed the detrimental effect caused by PTRF on the adipose tissue to the existence of senescent adipocyte precursors unable to proliferate and differentiate into adipocytes. This study provides evidence that impaired adipocyte functionality can be corrected, at least partially, by PTRF downregulation and warrants further in vivo research in patients with dysfunctional adipose tissue to prevent metabolic complications.
Region-specific role for Pten in maintenance of epithelial phenotype and integrity
Authors: Flodby Per , Liebler Janice M. , Sunohara Mitsuhiro , Castillo Dan R. , McConnell Alicia M. , Krishnaveni Manda S. , Banfalvi Agnes , Li Min , Stripp Barry , Zhou Beiyun , Crandall Edward D. , Minoo Parviz , Borok Zea
Published: November 2016

Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional PtenSFTPC-cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells toward the luminal aspect of the hyperplastic epithelium. Bronchiolar epithelial and alveolar epithelial type II (AT2) cells in PtenSFTPC-cre mice showed decreased expression of epithelial markers and increased expression of mesenchymal markers, suggesting at least partial epithelial-mesenchymal transition at baseline. Surprisingly, and in contrast to previous studies, mutant mice were exquisitely sensitive to bleomycin, manifesting rapid weight loss, respiratory distress, increased early mortality (by day 5), and reduced dynamic lung compliance. This was accompanied by sloughing of the hyperplastic airway epithelium with occlusion of small bronchioles by cellular debris, without evidence of increased parenchymal lung injury. Increased airway epithelial cell apoptosis due to loss of antioxidant defenses, reflected by decreased expression of superoxide dismutase 3, in combination with deficient intercellular adhesion, likely predisposed to airway sloughing in knockout mice. These findings demonstrate an important role for Pten in maintenance of airway epithelial phenotype integrity and indicate that responses to Pten deletion in respiratory epithelium following acute lung injury are highly context-dependent and region-specific.
Effect of increased and maintained frequency of speed endurance training on performance and muscle adaptations in runners
Authors: Skovgaard Casper , Almquist Nicki Winfield , Bangsbo Jens
Published: November 2016

The aim of the study was, in runners accustomed to speed endurance training (SET), to examine the effect of increased and maintained frequency of SET on performance and muscular adaptations. After familiarization (FAM) to SET, 18 male ( n = 14) and female ( n = 4) runners (V̇o2max: 57.3 ± 3.4 ml/min; means ± SD) completed 20 sessions of maintained low-frequency (LF; every fourth day; n = 7) or high-frequency (HF; every second day; n = 11) SET. Before FAM as well as before and after an intervention period (INT), subjects completed a series of running tests and a biopsy from m. vastus lateralis was collected. Ten-kilometer performance improved ( P < 0.05) ~3.5% during FAM with no further change during INT. Time to exhaustion at 90% vV̇o2max was 15 and 22% longer ( P < 0.05) during FAM and a further 12 and 16% longer ( P < 0.05) during INT in HF and LF, respectively. During FAM, muscle expression of NHE1 and maximal activity of citrate synthase (CS) and phosphofructokinase (PFK) increased ( P < 0.05), running economy (RE) improved ( P < 0.05), and V̇o2max was unchanged. During INT, both HF and LF increased ( P < 0.05) muscle expression of NKAβ1, whereas maximal activity of CS and PFK, RE, and V̇o2max were unchanged. Furthermore, during INT, muscle expression of FXYD1 and SERCA1, and FXYD1 activity increased ( P < 0.05) in HF, while muscle expression of SERCA2 decreased ( P < 0.05) in LF. Thus increased or maintained frequency of SET leads to further improvements in short-term exercise capacity, but not in 10-km running performance. The better short-term exercise capacity may be associated with elevated expression of muscle proteins related to Na+/K+ transportation and Ca2+ reuptake.

NEW & NOTEWORTHY Ten speed endurance training (SET) sessions improved short-term exercise capacity and 10-km performance, which was followed by further improved short-term exercise capacity, but unchanged 10-km performance after 20 SET sessions performed with either high frequency (4 per 8 days) or continued low frequency (2 per 8 days) in trained runners. The further gain in short-term exercise capacity was associated with changes in muscle expression of proteins of importance for the development of fatigue.
Axl Blockade by BGB324 Inhibits BCR-ABL Tyrosine Kinase Inhibitor–Sensitive and -Resistant Chronic Myeloid Leukemia
Authors: Ben-Batalla Isabel , Erdmann Robert , Jørgensen Heather , Mitchell Rebecca , Ernst Thomas , von Amsberg Gunhild , Schafhausen Philippe , Velthaus Janna L. , Rankin Stephen , Clark Richard E. , Koschmieder Steffen , Schultze Alexander , Mitra Subir , Vandenberghe Peter , Brümmendorf Tim H. , Carmeliet Peter , Hochhaus Andreas , Pantel Klaus , Bokemeyer Carsten , Helgason G. Vignir , Holyoake Tessa L. , Loges Sonja
Published: November 2016

Purpose: BCR-ABL kinase inhibitors are employed successfully for chronic myeloid leukemia (CML) treatment. However, resistant disease and persistence of BCR-ABL1–independent leukemia stem and progenitor cells (LSPC) remain clinical challenges. The receptor tyrosine kinase Axl can mediate survival and therapy resistance of different cancer cells. We investigated the therapeutic potential of Axl inhibition in CML.

Experimental Design: We used primary cells from patients with CML and TKI-sensitive and -resistant BCR-ABL1+ CML cell lines and a novel ponatinib-resistant cell line KCL-22 PonR. We analyzed the effects of genetic and pharmacologic Axl blockade by the small-molecule Axl inhibitor BGB324 in vitro and in vivo. In BCR-ABL1–unmutated cells, we also investigated BGB324 in combination with imatinib.

Results: We demonstrate overexpression of Axl receptor tyrosine kinase in primary cells of patients with CML compared with healthy individuals and a further increase of Axl expression in BCR-ABL TKI-resistant patients. We show that Axl blockage decreased growth of BCR-ABL TKI-sensitive CML cells including CD34+ cells and exerts additive effects with imatinib via inhibition of Stat5 activation. BGB324 also inhibits BCR-ABL TKI-resistant cells, including T315I-mutated and ponatinib-resistant primary cells. BGB324 exerted therapeutic effects in BCR-ABL1 T315I-mutated and ponatinib-resistant preclinical mouse models. Notably, BGB324 does not inhibit BCR-ABL1 and consequently inhibits CML independent of BCR-ABL1 mutational status.

Conclusions: Our data show that Axl inhibition has therapeutic potential in BCR-ABL TKI-sensitive as well as -resistant CML and support the need for clinical trials. Clin Cancer Res; 23(9); 2289–300. ©2016 AACR.