Knowledge-based planning in robotic intracranial stereotactic radiosurgery treatments

PURPOSE: To develop a knowledge-based planning (KBP) model that predicts dosimetric indices and facilitates planning in CyberKnife intracranial stereotactic radiosurgery/radiotherapy (SRS/SRT). METHODS: Forty CyberKnife SRS/SRT plans were retrospectively used to build a linear KBP model which correlated the equivalent radius of the PTV (req_PTV ) and the equivalent radius of volume that receives a set of prescription dose (req_Vi , where Vi = V10% , V20% ... V120% ). To evaluate the model\u27s predictability, a fourfold cross-validation was performed for dosimetric indices such as gradient measure (GM) and brain V50% . The accuracy of the prediction was quantified by the mean and the standard deviation of the difference between planned and predicted values, (i.e., DeltaGM = GMpred - GMclin and fractional DeltaV50% = (V50%pred - V50%clin )/V50%clin ) and a coefficient of determination, R(2) . Then, the KBP model was incorporated into the planning for another 22 clinical cases. The training plans and the KBP test plans were compared in terms of the new conformity index (nCI) as well as the planning efficiency. RESULTS: Our KBP model showed desirable predictability. For the 40 training plans, the average prediction error from cross-validation was only 0.36 +/- 0.06 mm for DeltaGM, and 0.12 +/- 0.08 for DeltaV50% . The R(2) for the linear fit between req_PTV and req_vi was 0.985 +/- 0.019 for isodose volumes ranging from V10% to V120% ; particularly, R(2) = 0.995 for V50% and R(2) = 0.997 for V100% . Compared to the training plans, our KBP test plan nCI was improved from 1.31 +/- 0.15 to 1.15 +/- 0.08 (P \u3c 0.0001). The efficient automatic generation of the optimization constraints by using our model requested no or little planner\u27s intervention. CONCLUSION: We demonstrated a linear KBP based on PTV volumes that accurately predicts CyberKnife SRS/SRT planning dosimetric indices and greatly helps achieve superior plan quality and planning efficiency

Hertz-linewidth semiconductor lasers using CMOS-ready ultra-high-QQ microresonators

Driven by narrow-linewidth bench-top lasers, coherent optical systems spanning optical communications, metrology and sensing provide unrivalled performance. To transfer these capabilities from the laboratory to the real world, a key missing ingredient is a mass-produced integrated laser with superior coherence. Here, we bridge conventional semiconductor lasers and coherent optical systems using CMOS-foundry-fabricated microresonators with record high $Q$ factor over 260 million and finesse over 42,000. Five orders-of-magnitude noise reduction in the pump laser is demonstrated, and for the first time, fundamental noise below 1 Hz$^2$ Hz$^{-1}$ is achieved in an electrically-pumped integrated laser. Moreover, the same configuration is shown to relieve dispersion requirements for microcomb generation that have handicapped certain nonlinear platforms. The simultaneous realization of record-high $Q$ factor, highly coherent lasers and frequency combs using foundry-based technologies paves the way for volume manufacturing of a wide range of coherent optical systems.Comment: 19 pages, 11 figure

Leveraging Pleiotropy to Discover and interpret Gwas Results For Sleep-Associated Traits

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations in underpowered validation cohorts and leads to higher interpretability. Here, as an exemplar, we use Obstructive Sleep Apnea (OSA), a common disorder diagnosed using overnight multi-channel physiological testing. We leverage pleiotropy with relevant cellular and cardio-metabolic phenotypes and gene expression traits to map new risk loci in an underpowered OSA GWAS. We identify several pleiotropic loci harboring suggestive associations to OSA and genome-wide significant associations to other traits, and show that their OSA association replicates in independent cohorts of diverse ancestries. By investigating pleiotropic loci, our strategy allows proposing new hypotheses about OSA pathobiology across many physiological layers. For example, we identify and replicate the pleiotropy across the plateletcrit, OSA and an eQTL of DNA primase subunit 1 (PRIM1) in immune cells. We find suggestive links between OSA, a measure of lung function (FEV1/FVC), and an eQTL of matrix metallopeptidase 15 (MMP15) in lung tissue. We also link a previously known genome-wide significant peak for OSA in the hexokinase 1 (HK1) locus to hematocrit and other red blood cell related traits. Thus, the analysis of pleiotropic associations has the potential to assemble diverse phenotypes into a chain of mechanistic hypotheses that provide insight into the pathogenesis of complex human diseases

Genotyping-by-Sequencing and Ecological Niche Modeling Illuminate Phylogeography, Admixture, and Pleistocene Range Dynamics in Quaking Aspen (Populus Tremuloides)

Populus tremuloides is the widest‐ranging tree species in North America and an ecologically important component of mesic forest ecosystems displaced by the Pleistocene glaciations. Using phylogeographic analyses of genome‐wide SNPs (34,796 SNPs, 183 individuals) and ecological niche modeling, we inferred population structure, ploidy levels, admixture, and Pleistocene range dynamics of P. tremuloides, and tested several historical biogeographical hypotheses. We found three genetic lineages located mainly in coastal–Cascades (cluster 1), east‐slope Cascades–Sierra Nevadas–Northern Rockies (cluster 2), and U.S. Rocky Mountains through southern Canadian (cluster 3) regions of the P. tremuloides range, with tree graph relationships of the form ((cluster 1, cluster 2), cluster 3). Populations consisted mainly of diploids (86%) but also small numbers of triploids (12%) and tetraploids (1%), and ploidy did not adversely affect our genetic inferences. The main vector of admixture was from cluster 3 into cluster 2, with the admixture zone trending northwest through the Rocky Mountains along a recognized phenotypic cline (Utah to Idaho). Clusters 1 and 2 provided strong support for the “stable‐edge hypothesis” that unglaciated southwestern populations persisted in situ since the last glaciation. By contrast, despite a lack of clinal genetic variation, cluster 3 exhibited “trailing‐edge” dynamics from niche suitability predictions signifying complete northward postglacial expansion. Results were also consistent with the “inland dispersal hypothesis” predicting postglacial assembly of Pacific Northwestern forest ecosystems, but rejected the hypothesis that Pacific‐coastal populations were colonized during outburst flooding from glacial Lake Missoula. Overall, congruent patterns between our phylogeographic and ecological niche modeling results and fossil pollen data demonstrate complex mixtures of stable‐edge, refugial locations, and postglacial expansion within P. tremuloides. These findings confirm and refine previous genetic studies, while strongly supporting a distinct Pacific‐coastal genetic lineage of quaking aspen

Integrated Pockels Laser

The development of integrated semiconductor lasers has miniaturized traditional bulky laser systems, enabling a wide range of photonic applications. A progression from pure III-V based lasers to III-V/external cavity structures has harnessed low-loss waveguides in different material systems, leading to significant improvements in laser coherence and stability. Despite these successes, however, key functions remain absent. In this work, we address a critical missing function by integrating the Pockels effect into a semiconductor laser. Using a hybrid integrated III-V/Lithium Niobate structure, we demonstrate several essential capabilities that have not existed in previous integrated lasers. These include a record-high frequency modulation speed of 2 exahertz/s (2.0$\times$10$^{18}$ Hz/s) and fast switching at 50 MHz, both of which are made possible by integration of the electro-optic effect. Moreover, the device co-lases at infrared and visible frequencies via the second-harmonic frequency conversion process, the first such integrated multi-color laser. Combined with its narrow linewidth and wide tunability, this new type of integrated laser holds promise for many applications including LiDAR, microwave photonics, atomic physics, and AR/VR

Yolk utilization and growth during the early larval life of the Silver Perch, Bidyanus bidyanus (Mitchell, 1838)

The aim of this research was to investigate the yolk sac and oil globule utilization by silver perch (Bidyanus bidyanus) larvae produced from domesticated broodfish. The larvae were kept unfed in the holding tank, sampled, and investigated by image analysis software to determine various characteristics, such as the diameters of ova, water-hardened eggs, yolk-sac, oil globules, and the total length of larvae. The research illustrated that, with the exception of oil globule diameter, all other morphometric parameters were significantly lower (P < 0.05) when compared to the larvae from the wild broodfish. The yolk sac was completely absorbed at 96 h post-hatching (hph) and the oil globule was visible until 240 hph. The larvae exhibited predatory movements and tried to catch rotifer at 4 days post hatching (dph). However, the onset of feeding took place at 5 dph, while 100% of feeding occurred at 6 dph. During the first 96 h (h), larvae grew significantly faster than the next 144 h. Larvae encountered low mortalities (<10%) during the first 96 hph, before increasing significantly in the next 24 h and no unfed larvae survived post 240 h. The results also suggested that the exogenous feed should be available at 96 hph, which is well after the yolk sac is completely depleted. In addition, although most of eggs and larval performance from domesticated broodfish were inferior compared to the wild one, it has larger oil globule that could make longer of its mixed feeding period and therefore could have better in viability