CyberKnife for hilar lung tumors: report of clinical response and toxicity

<p>Abstract</p> <p>Objective</p> <p>To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors.</p> <p>Methods</p> <p>Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals.</p> <p>Results</p> <p>Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy.</p> <p>Conclusion</p> <p>CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.</p

High-performance flexible perovskite solar cells exploiting Zn2SnO4 prepared in solution below 100 degrees C

Fabricating inorganic-organic hybrid perovskite solar cells (PSCs) on plastic substrates broadens their scope for implementation in real systems by imparting portability, conformability and allowing high-throughput production, which is necessary for lowering costs. Here we report a new route to prepare highly dispersed Zn2SnO4 (ZSO) nanoparticles at low-temperature (<100 degrees C) for the development of high-performance flexible PSCs. The introduction of the ZSO film significantly improves transmittance of flexible polyethylene naphthalate/indium-doped tin oxide (PEN/ITO)-coated substrate from similar to 75 to similar to 90% over the entire range of wavelengths. The best performing flexible PSC, based on the ZSO and CH3NH3PbI3 layer, exhibits steady-state power conversion efficiency (PCE) of 14.85% under AM 1.5G 100 mW . cm(-2) illumination. This renders ZSO a promising candidate as electron-conducting electrode for the highly efficient flexible PSC applications.ope

Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems

Three-dimensional bio-printing and bone tissue engineering: technical innovations and potential applications in maxillofacial reconstructive surgery

Background Bone grafting has been considered the gold standard for hard tissue reconstructive surgery and is widely used for large mandibular defect reconstruction. However, the midface encompasses delicate structures that are surrounded by a complex bone architecture, which makes bone grafting using traditional methods very challenging. Three-dimensional (3D) bioprinting is a developing technology that is derived from the evolution of additive manufacturing. It enables precise development of a scaffold from different available biomaterials that mimic the shape, size, and dimension of a defect without relying only on the surgeon’s skills and capabilities, and subsequently, may enhance surgical outcomes and, in turn, patient satisfaction and quality of life. Review This review summarizes different biomaterial classes that can be used in 3D bioprinters as bioinks to fabricate bone scaffolds, including polymers, bioceramics, and composites. It also describes the advantages and limitations of the three currently used 3D bioprinting technologies: inkjet bioprinting, micro-extrusion, and laser-assisted bioprinting. Conclusions Although 3D bioprinting technology is still in its infancy and requires further development and optimization both in biomaterials and techniques, it offers great promise and potential for facial reconstruction with improved outcome

Inferring causal molecular networks: empirical assessment through a community-based effort.

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Working passionately does not always pay off : the negative moderating role of passion on the relationship between deliberate practice and venture performance

Deliberate practice, an iterative process that leads to expertise, is found to be positively associated with superior performance in domains such as sports, education, and entrepreneurship. At the same time, deliberate practice is also seen as being less than enjoyable and difficult to pursue consistently. As such, passion is considered to be a vital motivator of engagement in and maintenance of deliberate practice. Despite the evident importance of passion, the relationship between passion and deliberate practice in entrepreneurship has not been subject to sufficient empirical evaluation. Therefore, in this study, we consider the way in which passion moderates the relationship between deliberate practice and venture performance. We hypothesize that deliberate practice is positively related to venture performance and that passion positively moderates this relationship. We find support for our first hypothesis, in line with previous studies. However, contrary to our second hypothesis, we find that entrepreneurial passion negatively moderates the deliberate practice-venture performance relationship. In response to this finding, we provide possible explanations as to why this negative moderation effect was observed by drawing on Kolb’s experiential learning cycle