bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigation of nitrous oxide emissions with nitrification inhibitors in temperate vegetable cropping in southern Australia
Authors: Riches D. A. , Mattner S. W. , Davies R. , Porter I. J.
Published: July 2016

Intensive vegetable production in southern Australia is characterised by high inputs of nitrogen (N) fertiliser, water, and occasionally animal manures, which creates the potential for high nitrous oxide (N2O) emissions. Three field experiments were conducted to investigate the effects of the nitrification inhibitors 3, 4-dimethylpyrazole phosphate (DMPP), 3-methyl pyrazole plus 1H-1,2,4 triazole (3MP+TZ), and dicyandiamide (DCD) on N2O emissions and yields in broccoli (Brassica oleracea), lettuce (Lactuca sativa) and cauliflower (Brassica oleracea) crops in southern Australia. The inhibitor treatments on fertilisers and poultry manure were compared with standard commercial practice for vegetable crops in this region, and N2O emissions were measured using manual chambers through to harvest. Daily fluxes ranged from 0.81gN2O-Nha–1day–1 for untreated soil to 11.65gN2O-Nha–1day–1 for manure treated soil. Extrapolation of these results translate to annual emissions of 0.30kgN2O-Nha–1year–1 to 4.24kgN2O-Nha–1year–1, respectively. Cumulative soil N2O fluxes from the manure treatments were ~4-fold greater than the standard inorganic fertiliser program for a given crop. Nitrous oxide direct emission factors were in the range 0.02–0.16% for inorganic fertilisers and from 0.19% to 0.43% for poultry manure. The greatest decrease in N2O emissions occurred when DMPP or a combination of 3MP+TZ were added to poultry manure (62% and 66% decrease, respectively). Decreases in N2O emissions from nitrification inhibitors were smaller and less consistent when used with inorganic fertilisers, but DMPP decreased emissions in two out of three trials, with a maximum decrease of 32% observed in the broccoli trial. DCD proved ineffective for mitigating N2O emissions in all trials.
Comparison of grain yields and N2O emissions on Oxisol and Vertisol soils in response to fertiliser N applied as urea or urea coated with the nitrification inhibitor 3,4-dimethylpyrazole phosphate
Authors: De Antoni Migliorati Massimiliano , Bell Mike , Lester David , Rowlings David W. , Scheer Clemens , de Rosa Daniele , Grace Peter R.
Published: July 2016

The potential for elevated nitrous oxide (N2O) losses is high in subtropical cereal cropping systems in north-east Australia, where the fertiliser nitrogen (N) input is one single application at or before planting. The use of urea coated with the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) has been reported to substantially decrease N2O emissions and increase crop yields in humid, high-intensity rainfall environments. However, it is still uncertain whether this product is similarly effective in contrasting soil types in the cropping region of north-east Australia. In this study the grain yield response of sorghum (Sorghum bicolor L. Moench) to rates of fertiliser N applied as urea or urea coated with DMPP were compared in crops grown on a Vertisol and an Oxisol in southern Queensland. Seasonal N2O emissions were monitored on selected treatments for the duration of the cropping season and the early stages of a subsequent fallow period using a fully automated high-frequency greenhouse gas measuring system. On each soil the tested treatments included an unfertilised control (0kgNha–1) and two fertilised treatments chosen on the basis of delivering at least 90% of seasonal potential grain yield (160 and 120kgNha–1 on the Vertisol and Oxisol respectively) or at a common (suboptimal) rate at each site (80kgNha–1). During this study DMPP had a similar impact at both sites, clearly inhibiting nitrification for up to 8 weeks after fertiliser application. Despite the relatively dry seasonal conditions during most of the monitoring period, DMPP was effective in abating N2O emissions on both soils and on average reduced seasonal N2O emissions by 60% compared with conventional urea at fertiliser N rates equivalent to those producing 90% of site maximum grain yield. The significant abatement of N2O emissions observed with DMPP, however, did not translate into significant yield gains or improvements in agronomic efficiencies of fertiliser N use. These results may be due to the relatively dry growing season conditions before the bulk of crop N acquisition, which limited the exposure of fertiliser N to large losses due to leaching and denitrification.
Nitrous oxide emissions from grain production systems across a wide range of environmental conditions in eastern Australia
Authors: Mielenz Henrike , Thorburn Peter J. , Harris Robert H. , Officer Sally J. , Li Guangdi , Schwenke Graeme D. , Grace Peter R.
Published: July 2016

Nitrous oxide (N2O) emissions from Australian grain cropping systems are highly variable due to the large variations in soil and climate conditions and management practices under which crops are grown. Agricultural soils contribute 55% of national N2O emissions, and therefore mitigation of these emissions is important. In the present study, we explored N2O emissions, yield and emissions intensity in a range of management practices in grain crops across eastern Australia with the Agricultural Production Systems sIMulator (APSIM). The model was initially evaluated against experiments conducted at six field sites across major grain-growing regions in eastern Australia. Measured yields for all crops used in the experiments (wheat, barley, sorghum, maize, cotton, canola and chickpea) and seasonal N2O emissions were satisfactorily predicted with R2=0.93 and R2=0.91 respectively. As expected, N2O emissions and emissions intensity increased with increasing nitrogen (N) fertiliser input, whereas crop yields increased until a yield plateau was reached at a site- and crop-specific N rate. The mitigation potential of splitting N fertiliser application depended on the climate conditions and was found to be relevant only in the southern grain-growing region, where most rainfall occurs during the cropping season. Growing grain legumes in rotation with cereal crops has great potential to reduce mineral N fertiliser requirements and so N2O emissions. In general, N management strategies that maximise yields and increase N use efficiency showed the greatest promise for N2O mitigation.
Grasses suppress shoot-borne roots to conserve water during drought
Authors: Sebastian Jose , Yee Muh-Ching , Goudinho Viana Willian , Rellán-Álvarez Rubén , Feldman Max , Priest Henry D. , Trontin Charlotte , Lee Tak , Jiang Hui , Baxter Ivan , Mockler Todd C. , Hochholdinger Frank , Brutnell Thomas P. , Dinneny José R.
Published: July 2016

Significance

Grasses, whose members constitute key food and bioenergy crops worldwide, use unique developmental programs to establish the root system from the shoot. Shoot-borne crown roots originate near the soil surface and provide the main conduits through which the plant takes up water and nutrients. We show that crown root development is the major target of drought stress signaling. Water deficit-triggered crown root arrest provides an important mechanism to conserve water under drought, and this response is widely conserved across grass species. Substantial phenotypic variation exists in maize for this trait, which may be a useful target in breeding efforts to improve drought tolerance.
Is Public Capital Productive? Evidence from a Meta‐analysis
Authors: Núñez‐Serrano Juan A. , Velázquez Francisco J.
Published: July 2016

Debate exists over the role that public investment must play in economic recovery and economic growth. The underlying idea behind this debate has much to do with the value of output elasticity of public capital. This article presents a meta‐analysis of this elasticity, which was performed by considering almost 2,000 elasticities previously estimated from 145 papers. In addition, for each elasticity, we also take into account some 30 associated features relative to the methodology used for each case or relative to the characteristics of data samples. The obtained results reveal an average short‐term elasticity of 0.13 (0.16 in the long term). We also find evidence of the importance of the methodology adopted for the obtained results, as well as the publication bias. Finally, we find a minor reduction in the value of the elasticity as public capital endowments increase. The results obtained highlight the positive and important effect of public investment on productivity. As a results of the value obtained, public investment will be self‐financed in the long‐term because of generated returns. But, we also find that the effectiveness of public investment has a clear influence of the institutional context.
Necessary and sufficient conditions for multi-agent controllability of path and star topologies by exploring the information of second-order neighbours
Authors: Chao Yongcui , Ji Zhijian
Published: July 2016

This article investigates the controllability of path and star graphs under the protocol of second-order neighbours. With identified special control nodes, a sufficient condition is first derived for the controllability of path graph by taking advantage of the protocol of second-order neighbours. Then necessary and sufficient conditions are developed respectively for the single and multiple leaders. Some differences between the protocol of second-order neighbours and first-order neighbours are also presented for path graph. Finally, a necessary and sufficient condition is proposed for the controllability of star graph by taking advantage of the protocol of second-order neighbours.
Metabolic tumor volume on FDG-PET/CT is a possible prognostic factor for Stage I lung cancer patients treated with stereotactic body radiation therapy: a retrospective clinical study
Authors: Takahashi Noriyoshi , Yamamoto Takaya , Matsushita Haruo , Sugawara Toshiyuki , Kubozono Masaki , Umezawa Rei , Ishikawa Yojiro , Kozumi Maiko , Katagiri Yu , Tasaka Syun , Takeda Kazuya , Takeda Ken , Dobashi Suguru , Jingu Keiichi
Published: July 2016

The aim of this study was to determine whether metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are associated with outcomes in Stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT). Thirty-eight patients underwent [18F] fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) within 60 days before SBRT at our institution between January 2001 and December 2011. The maximum standardized uptake value (SUVmax), MTV2, MTV4, MTV6, TLG40%, TLG50% and TLG60% were calculated. Prognostic factors for overall survival (OS) and local control (LC) were analyzed using Cox's proportional hazards model, and survival curves were calculated using the Kaplan–Meier method. Receiver operating characteristics (ROC) curves of PET parameters for OS and LC were calculated. The median follow-up period for survivors was 37.7 months. Three-year OS and LC rates were 56.4% and 70.5%, respectively, and 5-year OS and LC rates were 36.8% and 70.5%, respectively. In univariate analyses, tumor diameter (P = 0.019), single dose ≥10 Gy (P = 0.017), MTV2 (P = 0.030) and MTV4 (P = 0.048) were significant predictors for OS. Tumor diameter (P < 0.001), single dose ≥10 Gy (P = 0.007), SUVmax (P = 0.035), MTV2 (P < 0.001), MTV4 (P = 0.003), MTV6 (P = 0.017), TLG40% (P < 0.001), TLG50% (P = 0.001) and TLG60% (P = 0.003) were significant predictors for LC. SUVmax was not a significant predictor for OS. We made the ROC curves at PET parameters, and the largest area under the curve value for OS was MTV2 and for LC was TLG40%. Tumor diameter, single dose ≥10 Gy, MTV2 and MTV4 are prognostic factors for OS and LC rates and MTV2 is a better prognostic factor for OS than other PET parameters.
Post-mastectomy radiation therapy without usage of a bolus may be a reasonable option
Authors: Nakamura Naoki , Arahira Satoko , Zenda Sadamoto , Yoneyama Kimiyasu , Mukai Hirofumi , Onozawa Masakatsu , Toshima Masamichi , Motegi Atsushi , Hirano Yasuhiro , Hojo Hidehiro , Kibe Yuichi , Akimoto Tetsuo
Published: July 2016

To clarify the efficacy and toxicity of post-mastectomy radiation therapy (PMRT) without usage of a bolus, we identified 129 consecutive patients who received PMRT at the National Cancer Center Hospital East between 2003 and 2012. Seven of the 129 patients who received breast reconstruction before PMRT were excluded. All patients received PMRT of 6 MV photons, without usage of a bolus. The median follow-up duration for all eligible patients was 47.7 months (range: 4.0–123.2). Local, locoregional and isolated locoregional recurrence was found in 12 (9.8%), 14 (11%) and 5 patients (4.1%), respectively. The 3- and 5-year cumulative incidence of local recurrence, locoregional recurrence and isolated locoregional recurrence was 9.2 and 10.7%, 10.8 and 12.4%, and 4.3 and 4.3%, respectively. Although Grade 2 dermatitis was found in 11 patients (9.0%), no Grade 3–4 dermatitis was found. On univariate analysis, only a non-luminal subtype was a significant predictor for local recurrence (P < 0.001). On multivariate analysis, a non-luminal subtype remained as an independent predictor for local recurrence (P = 0.003, odds ratio: 10.9, 95% confidence interval: 2.23–53.1). In conclusion, PMRT without usage of a bolus resulted in a low rate of severe acute dermatitis without an apparent increase in local recurrence. PMRT without usage of a bolus may be reasonable, especially for patients with a luminal subtype.
Regional recurrence in breast cancer patients with one to three positive axillary lymph nodes treated with breast-conserving surgery and whole breast irradiation
Authors: Hirata Kimiko , Yoshimura Michio , Inoue Minoru , Yamauchi Chikako , Ogura Masakazu , Toi Masakazu , Suzuki Eiji , Takeuchi Megumi , Takada Masahiro , Hiraoka Masahiro
Published: July 2016

Radiotherapy with breast-conserving therapy plays a crucial role in the treatment of early breast cancer. However, optimal radiotherapy targets have been controversial. We therefore evaluated regional recurrence in breast cancer patients with one to three positive lymph nodes (LNs) treated with breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI). From 1993 to 2010, 121 breast cancer patients with one to three positive LNs who underwent BCS followed by WBI were analyzed. All patients underwent radiotherapy with two tangential fields to the whole breast. To evaluate the radiation dose to the axillary LNs, we contoured axillary LNs area and evaluated the dose–volumetric parameters. The median follow-up time was 112.4 months (range, 15.6–248.1 months). The 5-year overall survival and disease-free survival rates were 95.6% and 86.6%, respectively. The 5-year regional recurrence–free rate (RRFR) was 97.4%. During follow-up, six patients had regional recurrence. The pathological T stage was the factor best associated with the 5-year RRFR using the log-rank test, with 100.0% in the pT1 cohort versus 94.7% in the pT2–4 cohort (P < 0.01). The radiation dose to the axillary LNs did not contribute to the RRFR. In conclusion, while the pathological T stage was the prognostic factor best associated with regional recurrence, few regional recurrences were observed in early breast cancer patients with one to three LNs treated with BCS followed by WBI. Unintentional radiation doses to the axillary LNs using standard WBI were not related to the RRFR after axillary dissection.
Selection bias in dynamically measured supermassive black hole samples: consequences for pulsar timing arrays
Authors: Sesana Alberto , Shankar Francesco , Bernardi Mariangela , Sheth Ravi K.
Published: July 2016

Supermassive black hole–host galaxy relations are key to the computation of the expected gravitational wave background (GWB) in the pulsar timing array (PTA) frequency band. It has been recently pointed out that standard relations adopted in GWB computations are in fact biased-high. We show that when this selection bias is taken into account, the expected GWB in the PTA band is a factor of about 3 smaller than previously estimated. Compared to other scaling relations recently published in the literature, the median amplitude of the signal at f = 1 yr−1 drops from 1.3 × 10−15 to 4 × 10−16. Although this solves any potential tension between theoretical predictions and recent PTA limits without invoking other dynamical effects (such as stalling, eccentricity or strong coupling with the galactic environment), it also makes the GWB detection more challenging.
Dipper discs not inclined towards edge-on orbits
Authors: Ansdell M. , Gaidos E. , Williams J. P. , Kennedy  G. , Wyatt M. C. , LaCourse D. M. , Jacobs T. L. , Mann A. W.
Published: July 2016

The so-called dipper stars host circumstellar discs and have optical and infrared light curves that exhibit quasi-periodic or aperiodic dimming events consistent with extinction by transiting dusty structures orbiting in the inner disc. Most of the proposed mechanisms explaining the dips – i.e. occulting disc warps, vortices, and forming planetesimals – assume nearly edge-on viewing geometries. However, our analysis of the three known dippers with publicly available resolved sub-mm data reveals discs with a range of inclinations, most notably the face-on transition disc J1604-2130 (EPIC 204638512). This suggests that nearly edge-on viewing geometries are not a defining characteristic of the dippers and that additional models should be explored. If confirmed by further observations of more dippers, this would point to inner disc processes that regularly produce dusty structures far above the outer disc mid-plane in regions relevant to planet formation.
Discovery of a high state AM CVn binary in the Galactic Bulge Survey
Authors: Wevers T. , Torres M. A. P. , Jonker P. G. , Wetuski J. D. , Nelemans G. , Steeghs D. , Maccarone T. J. , Heinke C. , Hynes R. I. , Udalski A. , Kostrzewa-Rutkowska Z. , Groot P. J. , Gazer R. , Szymański M. K. , Britt C. T. , Wyrzykowski Ł. , Poleski R.
Published: July 2016

We report on the discovery of a hydrogen-deficient compact binary (CXOGBS J175107.6-294037) belonging to the AM CVn class in the Galactic Bulge Survey. Deep archival X-ray observations constrain the X-ray positional uncertainty of the source to 0.57 arcsec, and allow us to uniquely identify the optical and UV counterpart. Optical spectroscopic observations reveal the presence of broad, shallow He i absorption lines while no sign of hydrogen is present, consistent with a high state system. We present the optical light curve from Optical Gravitational Lensing Experiment monitoring, spanning 15 yr. It shows no evidence for outbursts; variability is present at the 0.2 mag level on time-scales ranging from hours to weeks. A modulation on a time-scale of years is also observed. A Lomb–Scargle analysis of the optical light curves shows two significant periodicities at 22.90 and 23.22 min. Although the physical interpretation is uncertain, such time-scales are in line with expectations for the orbital and superhump periods. We estimate the distance to the source to be between 0.5 and 1.1 kpc. Spectroscopic follow-up observations are required to establish the orbital period, and to determine whether this source can serve as a verification binary for the eLISA gravitational wave mission.
Surface Dielectric Resonators for X-band EPR Spectroscopy
Authors: Petryakov Sergey V. , Schreiber Wilson , Kmiec Maciej M. , Williams Benjamin B. , Swartz Harold M.
Published: July 2016

A new resonator for X-band electron paramagnetic resonance (EPR) spectroscopy, which utilizes the unique resonance properties of dielectric substrates, has been developed using a single crystal of titanium dioxide. As a result of the dielectric properties of the crystal(s) chosen, this novel resonator provides the ability to make in vivo EPR spectroscopy surface measurements in the presence of lossy tissues at X-band frequencies (up to 10 GHz). A double-loop coupling device is used to transmit and receive microwave power to/from the resonator. This coupler has been developed and optimized for coupling to the resonator in the presence of lossy tissues to further enable in vivo measurements, such as in vivo EPR spectroscopy of human fingernails or teeth to measure the dose of ionizing radiation that a given individual has been exposed to. An advantage of this resonator for surface measurements is that the magnetic fields generated by the resonator are inherently shallow, which is desirable for in vivo nail dosimetry.
Measuring the Cognitions, Emotions, and Motivation Associated With Avoidance Behaviors in the Context of Pain
Authors: Jensen Mark P. , Ward L. Charles , Thorn Beverly E. , Ehde Dawn M. , Day Melissa A.
Published: July 2016

Objectives:

We recently proposed a Behavioral Inhibition System-Behavioral Activation System (BIS-BAS) model to help explain the effects of pain treatments. In this model, treatments are hypothesized to operate primarily through their effects on the domains within 2 distinct neurophysiological systems that underlie approach (BAS) and avoidance (BIS) behaviors. Measures of the model’s domains are needed to evaluate and modify the model.

Methods:

An item pool of negative responses to pain (NRP; hypothesized to be BIS related) and positive responses (PR; hypothesized to be BAS related) were administered to 395 undergraduates, 325 of whom endorsed recurrent pain. The items were administered to 176 of these individuals again 1 week later. Analyses were conducted to develop and validate scales assessing NRP and PR domains.

Results:

Three NRP scales (Despondent Response to Pain, Fear of Pain, and Avoidant Response to Pain) and 2 PR scales (Happy/Hopeful Responses and Approach Response) emerged. Consistent with the model, the scales formed 2 relatively independent overarching domains. The scales also demonstrated excellent internal consistency, and associations with criterion variables supported their validity. However, whereas the NRP scales evidenced adequate test-retest stability, the 2 PR scales were not adequately stable.

Discussion:

The study yielded 3 brief scales assessing NRP, which may be used to further evaluate the BIS-BAS model and to advance research elucidating the mechanisms of psychosocial pain treatments. The findings also provide general support for the BIS-BAS model, while also suggesting that some minor modifications in the model are warranted.
Regenerative Intervertebral Disc Endplate Based on Biomimetic Three-dimensional Scaffolds
Authors: Yuan Dechao , Chen Zhu , Zhou Yuchuan , Xiao Dongqin , Liu Kang , Xiang Xiaocong , Deng Li , Dong Hua , Feng Gang
Published: July 2016

Study Design.

Fabrication and characterization of a regenerative intervertebral disc (IVD) cartilaginous endplate (CEP) based on tissue culturing on biomimetic scaffolds.

Objective.

To fabricate a regenerative CEP to support nutrients and metabolites exchange between IVD and the milieu interior.

Summary of Background Data.

CEP is the only pathway for most cells inside IVD to obtain nutrients and to eliminate metabolites. However, CEP usually fails at the same time when IVD degenerates. Therefore, reconstruction of CEP becomes an inevitable part of IVD regeneration. In this work, a novel regenerative CEP is fabricated to support nutrients and metabolites exchange of IVD.

Methods.

Three-dimensional scaffolds were fabricated by crosslinking of hyaluronic acid, chondroitin sulfate, and type II collagen. Then chondrocytes were cultured on the scaffolds. The obtained tissue was then investigated by scanning electron microscope, mechanical tests, and immunohistochemistry tests. In the end, glucose and lactic acid diffusion was carried out to test its nutrients and metabolites exchanging property.

Results.

Scanning electron microscopy investigations show that the 3-dimensional scaffold has microporous structure. After cell culturing, the inner structure of the obtained product becomes compact. Mechanical tests show that the obtained tissue has strong mechanical property. Immunohistochemistry tests show that the chemical compositions of the fabricated regenerative CEP are the same as its natural counterpart. Moreover, glucose and lactic acid diffuse through the regenerative CEP successfully.

Conclusion.

The fabricated regenerative CEP shows features similar to its natural counterpart. As the most important function, nutrients and metabolites exchange is verified on it as well. This regenerative CEP may play an important role in overall fabrication of regenerative IVD in near future.

Level of Evidence: N/A
Short-Term Organ Dysfunction Is Associated With Long-Term (10-Yr) Mortality of Septic Shock
Authors: Linder Adam , Lee Terry , Fisher Jane , Singer Joel , Boyd John , Walley Keith R. , Russell James A.
Published: July 2016

Objectives:

As mortality of septic shock decreases, new therapies focus on improving short-term organ dysfunction. However, it is not known whether short-term organ dysfunction is associated with long-term mortality of septic shock.

Design:

Retrospective single-center.

Setting:

Mixed medical-surgical ICU.

Patients:

One thousand three hundred and thirty-one patients with septic shock were included from 2000-2004. To remove the bias of 28-day nonsurvivors’ obvious association with long-term mortality, we determined the associations of days alive and free of ventilation, vasopressors and renal replacement therapy in 28-day and 1-year survivors with 1-, 5- and 10-year mortality in unadjusted analyses and analyses adjusted for age, gender, Acute Physiology and Chronic Health Evaluation II and presence of chronic comorbidities.

Interventions:

None.

Measurements and Main Results:

Days alive and free of ventilation, vasopressors, and renal replacement therapy were highly significantly associated with 1-, 5-, and 10-year mortality (p < 0.0001). In 28-day survivors, using Bonferroni-corrected multiple logistic regression, days alive and free of ventilation (p < 0.0001, p = 0.0002, and p = 0.001), vasopressors (p < 0.0001, p < 0.0001, and p = 0.0004), and renal replacement therapy (p = 0.0008, p = 0.0008, and p = 0.0002) were associated with increased 1-, 5-, and 10-year mortality, respectively. In 1-year survivors, none of the acute organ support and dysfunction measures were associated with 5- and 10-year mortality.

Conclusions:

Days alive and free of ventilation, vasopressors, and renal replacement therapy in septic shock in 28-day survivors was associated with 1-, 5-, and 10-year mortality. These associations are nullified in 1-year survivors in whom none of the acute organ support measures were associated with 5- and 10-year mortality. This suggests that therapies that decrease short-term organ dysfunction could also improve long-term outcomes of 28-day survivors of septic shock.
Current-day precision oncology: from cancer prevention, screening, drug development, and treatment – have we fallen short of the promise?
Authors: Morgan Gilberto , Aftimos Philippe , Awada Ahmad
Published: July 2016

Purpose of review

Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape.

Recent findings

The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs.

Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.
Low-cost Design and Manufacturing of Surgical Guides for Mandibular Reconstruction Using a Fibula
Authors: Numajiri Toshiaki , Nakamura Hiroko , Sowa Yoshihiro , Nishino Kenichi
Published: July 2016

Background:

Surgical cutting guides are used in mandibular reconstruction involving osteotomy of the mandible and fibula. Cutting guides produced using computer-aided design (CAD) and computer-aided manufacturing (CAM) technologies have been reported recently. These guides aim to increase the benefits to patients by improving the accuracy, shortening the operating time, and correcting occlusion. However, the availability of these advanced technologies is limited in some regions of the world. To test whether we could produce low-cost surgical cutting guides, we made surgical guides and investigated their accuracy.

Methods:

Using free CAD software, we designed surgical cutting guides for the mandible and fibula and used these to perform virtual mandibular segmental osteotomies and fibula transplants in 12 model surgeries. The cutting guides were printed on a 3-dimensional (3D) printer. The model surgeries were performed using 3D mandibular models and cutting guides to check their accuracy. Deviations between the virtually simulated plan and the actual model surgery were investigated.

Results:

CAD and CAM technologies were used to design and 3D print the cutting guides and models. The guided surgeries were performed. The deviations were about 1.3 mm for mandibular osteotomy, less than 1 mm for fibular osteotomy, and within 2.4 mm for reconstructions of the mandible.

Conclusions:

Without using expensive software or products, we were able to design surgical cutting guides for the mandible and fibula and used these to perform virtual simulation of mandibular segmental osteotomy and fibular reconstruction. Model surgeries using 3D-printed surgical guides showed that the accuracy of reconstruction was within a 3-mm deviation. In circumstances where commercial CAD/CAM guides are not available, it may be possible to use CAD/CAM surgical guides in the clinic if doctors are willing to volunteer their time for the design and printing.
The Opposite Expected Effect of p38 Inhibitors on Fat Graft Survival
Authors: Filson Simon A. , Keren Aviad , Goldstein Nyra , Ullmann Yehuda
Published: July 2016

Background:

Fat grafting is an increasingly popular method of augmentation/reconstruction of soft tissue defects. However, the clinical unpredictability and high resorption rates of the grafts remain problematic. Cellular stress from the harvest and the ensuing ischemic episode may be the cause of this. Cellular stress activates the p38 mitogen–activated protein kinase (MAPK) signaling pathway. In response to cellular stress, the p38 pathway can lead to apoptosis and can negatively regulate cell proliferation. Inhibition of p38 in ex vivo experiments has been shown to promote the expansion of human cord blood hematopoietic stem cell and improve the adipogenesis process through its upstream regulator, Shp2. Because of its wide-ranging cell regulation and antiinflammatory properties, large-scale clinical trials using p38 inhibitors are also currently being performed, especially for therapeutic effect in chronic obstructive pulmonary disease and asthma. The rationale for our study was that the treatment of fat grafts with p38 inhibitor would (a) prevent apoptosis of adipose-derived stem cells in the fat grafts, (b) increase adipose-derived stem cells proliferation, and (c) stimulate the release of several angiogenic factors and promote revascularization.

Methods:

Clinical and histological testing was performed on 5 fat-transplanted (1 mL) CD-1 nude mice compared with the test group of 5 mice, which were injected with a p38 MAPK inhibitor at 1, 3, 6, and 9 days after the fat transplantation.

Results:

The weights and volumes of the control group grafts were significantly higher than those of the p38 MAPK inhibitor–treated grafts. Average volume resorption was 36% in the control group and 92% in the test group. Histological evaluation of the grafts revealed significantly improved integration, with a significant reduction of fibrosis and inflammation in the control group versus the treated group.

Conclusions:

This preliminary study suggests that as opposed to our hypothesis, inhibition of p38 significantly increases fat graft resorption. The dramatic effects observed in our study may suggest that p38 may act differently on the numerous cell types that constitute the fat graft, and further investigation is necessary.
Hereditary Thrombophilia and Recurrent Pregnancy Loss
Authors: PRITCHARD ASHLEY M. , HENDRIX PAUL W. , PAIDAS MICHAEL J.
Published: July 2016

The challenging nature of recurrent pregnancy loss (RPL) is multifactorial, but largely begins with determining who meets diagnostic criteria for RPL as definitions vary and frequently change. Many patients seek obstetrical intervention after losses, even if they do not meet the criteria for RPL, and even those strictly meeting criteria often present a conundrum as to the etiology of their condition. The contribution of hereditary thrombophilia to RPL, the impact of each disorder on the clotting cascade, available evidence regarding pregnancy outcomes, and current recommendations for evaluation and treatment is presented.
Association Between Depressive Symptoms and Exercise Capacity in Patients With Heart Disease
Authors: Papasavvas Theodoros , Alhashemi Mohammad , Micklewright Dominic
Published: July 2016

Purpose:

Depression and reduced exercise capacity are risk factors for poor prognosis in patients with heart disease, but the relationship between the 2 is unclear. We assessed the relationship between depressive symptoms and exercise capacity in patients with heart disease.

Methods:

PubMed, Cochrane Library, Google Scholar, and ProQuest databases were browsed for English-language studies published from January 2000 to September 2013. Studies including adult patients with coronary artery disease, heart failure, congenital heart disease, and implantable cardioverter defibrillator, reporting correlation between a depression scale and exercise capacity (

JOURNAL/jcprh/04.03/01273116-201707000-00001/1FSM1/v/2023-09-11T074237Z/r/image-gif

o
2peak, peak watts, estimated metabolic equivalents, and incremental shuttle walk test distance), as well as studies from which such a correlation could be calculated and provided by the authors, were included. Correlation coefficients (CCs) were converted to Fischer z values, and the analysis was performed using a random-effects model. Then, summary effects and 95% CIs were converted back to CCs.

Results:

Fifty-nine studies (25 733 participants) were included. Depressive symptoms were inversely correlated to exercise capacity (CC = −0.15; 95% CI, −0.17 to −0.12). Heterogeneity was significant (I
2 = 64%; P < .001). There was no evidence of publication bias (Fail-safe N = 4681; Egger test: P = .06; Kendall test: P = .29).

Conclusions:

Patients with heart disease and elevated depressive symptoms may tend to have reduced exercise capacity, and vice versa. This finding has clinical and prognostic implications. It also encourages research on the effects of improving depression on exercise capacity, and vice versa. The effects of potential moderators need to be explored.
Pulmonary Rehabilitation Utilization in Older Adults With Chronic Obstructive Pulmonary Disease, 2003 to 2012
Authors: Nishi Shawn P. E. , Zhang Wei , Kuo Yong-Fang , Sharma Gulshan
Published: July 2016

PURPOSE:

To assess the trends in pulmonary rehabilitation (PR) utilization and factors associated with its use in older adults with chronic obstructive pulmonary disease (COPD).

METHODS:

We examined data for Medicare beneficiaries with COPD who received PR from January 1, 2003, to December 31, 2012. Persons with COPD were identified by (1) ≥2 outpatient visits >30 days apart within 1 year with an encounter diagnosis of COPD or (2) an acute care hospitalization with COPD as the primary diagnosis or a primary diagnosis of acute respiratory failure with a secondary discharge diagnosis of COPD. PR utilization was the study outcome identified by health care common procedure coding system codes G0237, G0238, G0239, and G0424 (after year 2010) or current procedural terminology codes (97001, 97003, 97110, 97116, 97124, 97139, 97150, 97530, 97535, and 97537) in a calendar year.

RESULTS:

Patients with COPD who received PR increased from 2.6% in 2003 to 3.7% in 2012 (P = .001). In a multivariable analysis, factors associated with receipt of PR were younger age, non-Hispanic white race, high socioeconomic status, multiple comorbidities (OR = 1.20; 95% CI = 1.13-1.27), and evaluation by a pulmonary physician (OR = 2.23; 95% CI = 2.13-2.33). Increased use of PR was attributed to prior users rather than new users of PR.

CONCLUSIONS:

Utilization of PR during the study period increased only 1.1% in these Medicare beneficiaries with COPD and remained low.
An intraorganizational model for developing and spreading quality improvement innovations
Authors: Kellogg Katherine C. , Gainer Lindsay A. , Allen Adrienne S. , O'Sullivan Tatum , Singer Sara J.
Published: July 2016

Background:

Recent policy reforms encourage quality improvement (QI) innovations in primary care, but practitioners lack clear guidance regarding spread inside organizations.

Purpose:

We designed this study to identify how large organizations can facilitate intraorganizational spread of QI innovations.

Methodology/Approach:

We conducted ethnographic observation and interviews in a large, multispecialty, community-based medical group that implemented three QI innovations across 10 primary care sites using a new method for intraorganizational process development and spread. We compared quantitative outcomes achieved through the group’s traditional versus new method, created a process model describing the steps in the new method, and identified barriers and facilitators at each step.

Findings:

The medical group achieved substantial improvement using its new method of intraorganizational process development and spread of QI innovations: standard work for rooming and depression screening, vaccine error rates and order compliance, and Pap smear error rates. Our model details nine critical steps for successful intraorganizational process development (set priorities, assess the current state, develop the new process, and measure and refine) and spread (develop support, disseminate information, facilitate peer-to-peer training, reinforce, and learn and adapt). Our results highlight the importance of utilizing preexisting organizational structures such as established communication channels, standardized roles, common workflows, formal authority, and performance measurement and feedback systems when developing and spreading QI processes inside an organization. In particular, we detail how formal process advocate positions in each site for each role can facilitate the spread of new processes.

Practice Implications:

Successful intraorganizational spread is possible and sustainable. Developing and spreading new QI processes across sites inside an organization requires creating a shared understanding of the necessary process steps, considering the barriers that may arise at each step, and leveraging preexisting organizational structures to facilitate intraorganizational process development and spread.
The role of health information technology in advancing care management and coordination in accountable care organizations
Authors: Wu Frances M. , Shortell Stephen M. , Rundall Thomas G. , Bloom Joan R.
Published: July 2016

Background:

To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes.

Purposes:

We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes.

Methodology/Approach:

Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index.

Findings:

HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (β = .41, p < .001), but the associations for information capture (β = −.01, p = .97) and information provision (β = .15, p = .48) functionalities were not significant.

Implications:

The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.
Expose or protect? A randomized controlled trial of exposure in vivo vs pain-contingent treatment as usual in patients with complex regional pain syndrome type 1
Authors: den Hollander Marlies , Goossens Mariëlle , de Jong Jeroen , Ruijgrok Joop , Oosterhof Jan , Onghena Patrick , Smeets Rob , Vlaeyen Johan W. S.
Published: July 2016

Complex regional pain syndrome type I (CRPS-I) highly affects patients' ability to perform daily life activities. Pain-related fear might be a key target to reduce disability in chronic pain. Current treatments aiming at reducing pain show little improvements on pain and disability, whereas novel exposure-based treatments targeting pain-related fears have shown to be promising. We conducted a randomized controlled trial (N = 46) comparing exposure in vivo (EXP) with pain-contingent treatment as usual (TAU), for CRPS-I patients with at least moderate levels of pain-related fear. Primary outcome is self-reported disability, for upper and lower extremity, respectively. Secondary outcomes are self-reported pain-intensity, pain-catastrophizing, perceived harmfulness of physical activity, and health-related quality of life. Pretreatment to posttreatment and pretreatment to 6-month follow-up change scores were tested using randomization-based inference. EXP was superior to TAU in reducing upper extremity disability from pretreatment to posttreatment (between-group difference, 1.082; 95% confidence interval [CI], 0.563-1.601; P < 0.001) and from pretreatment to 6-month follow-up (1.303; 95% CI, 0.917-1.690; P < 0.001). EXP was superior in reducing lower extremity disability from pretreatment to 6-month follow-up (3.624; 95% CI, 0.467-6.781; P = 0.02), but not from pretreatment to posttreatment (3.055; 95% CI, −0.018 to 6.128; P = 0.054). All secondary outcomes significantly favored EXP pretreatment to posttreatment, as well as pretreatment to 6-month follow-up. Exposure to daily activities shows to be more effective than a protective pain-contingent TAU in reducing self-reported disability in daily life of CRPS-I patients with at least moderate levels of pain-related fear.
Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain
Authors: Somogyi Andrew A. , Sia Alex T. , Tan Ene-Choo , Coller Janet K. , Hutchinson Mark R. , Barratt Daniel T.
Published: July 2016

Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2,TLR4,MYD88,MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA,TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition toOPRM1,COMT, andABCB1genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity,OPRM1rs1799971 (increased),TLR2rs3804100 (decreased), and an interaction between ethnicity andIL1Brs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained byIL1Brs1143634 (increased) andTGFB1rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variantCOMTrs4680 genotypes (P= 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.
Chronic physical illness in early life and risk of chronic widespread and regional pain at age 68: evidence from the 1946 British birth cohort
Authors: Muthuri Stella G. , Kuh Diana , Bendayan Rebecca , Macfarlane Gary J. , Cooper Rachel
Published: July 2016

This study aimed to examine the associations between serious illness in earlier life and risk of pain in old age using data from a large nationally representative British birth cohort, the Medical Research Council (MRC) National Survey of Health and Development (NSHD). Serious illness was defined as any experience of illness before age 25 requiring hospital admission of ≥28 days. Pain was self-reported at age 68, with chronic widespread pain (CWP) defined according to American College of Rheumatology criteria. Multinomial logistic regression was used to test associations of serious illness in early life with CWP, chronic regional pain (CRP), and other pain, with no pain as the referent category. Adjustment was made for sex, socioeconomic position, adult health status, health behaviours, and psychosocial factors. Of 2401 NSHD participants with complete data, 10.5% reported CWP (13.2% of women and 7.7% of men), 30.2% reported CRP, and 14.8% other pain. Compared with those with no history of serious illness, those who experienced serious illness in early life had a higher likelihood of CWP (relative risk ratio [RRR] = 1.62 [95% CI: 1.21-2.17]) and of CRP (RRR = 1.25 [95% CI: 1.01-1.54]) after adjusting for sex. In fully adjusted models, serious illness in early life remained associated with CWP (RRR = 1.43 [95% CI: 1.05-1.95]), but associations with CRP were attenuated (RRR = 1.19 [95% CI: 0.96-1.48]). There were no associations with other pain. These findings suggest that those who have experienced serious illness in earlier life may require more support than others to minimise their risk of CWP in later life.