Interstitial Insertion Research Articles

La(Fe,Si/Al)13-based materials with exceptional magnetic functionalities: a review

The field of magnetic functional materials continues to garner significant attention due to its research and diverse applications, such as magnetic storage and spintronics. Among these, La(Fe,Si/Al)13-based materials exhibit abundant magnetic properties and emerge as highly captivating subjects with immense potential. This review provides an overview of the diverse magnetic structures and itinerant electron metamagnetic transition observed in La(Fe,Si/Al)13-based materials. The transformation of different magnetic configurations elicits the phenomena such as negative thermal expansion, magnetostriction, magnetocaloric effect, and barocaloric effect. In addition, the pivotal role of spin and lattice coupling in these phenomena is revealed. The magnetic functionalities of La(Fe,Si/Al)13-based materials can be controlled through adjustments of magnetic exchange interactions. Key methods, including chemical substitution, external field application, and interstitial atom insertion, enable precise modulation of these functionalities. This review not only provides valuable insights into the design and development of magnetic functional materials but also offers significant contributions to our understanding of the underlying mechanisms governing their magnetic behaviors.

ATR blocks telomerase from converting DNA breaks into telomeres.

Telomerase, the enzyme that maintains telomeres at natural chromosome ends, should be repressed at double-strand breaks (DSBs), where neotelomere formation can cause terminal truncations. We developed an assay to detect neotelomere formation at Cas9- or I-SceI-induced DSBs in human cells. Telomerase added telomeric repeats to DSBs, leading to interstitial telomeric repeat insertions or the formation of functional neotelomeres accompanied by terminal deletions. The threat that telomerase poses to genome integrity was minimized by ataxia telangiectasia and Rad3-related (ATR) kinase signaling, which inhibited telomerase at resected DSBs. In addition to acting at resected DSBs, telomerase used the extruded strand in the Cas9 enzyme-product complex as a primer for neotelomere formation. We propose that although neotelomere formation is detrimental in normal human cells, it may allow cancer cells to escape from breakage-fusion-bridge cycles.

Efficacy and feasibility of 3D printed redesigned Venezia™ applicator for treating advanced cervix and recurrent endometrial cancer

PurposeVenezia™ is an interstitial brachytherapy applicator for treating advanced cervical and vaginal vault recurrent cancer. However, there are limitations that lead to suboptimal target coverage. 3D printing introduction allows the redesign of Venezia™ for bulky and irregular-shaped tumors. MethodsThis study first describes three new designs included: 1) add-on needles template allowed for an extra layer of straight and oblique needles, 2) redesigned vaginal cap so straight and oblique needles can be used together and 3) redesigned central tube allowed vaginal vault interstitial needle insertion. Drawbacks to original Venezia™ and rationale for using these new designs were discussed. Dosimetric analysis by comparing the original Venezia™ with new design for 10 cases in Oncentra treatment planning system v4.5 (Elekta, Stockholm, Sweden) to observe the dose differences in gross tumor volume (GTV), high risk clinical target volume (HRCTV), intermediate clinical target volume (IRCTV) and organs at risk. ResultsFor the dosimetric comparison, there were statistically significantly increased median minimal dose to 98% (D98%) of GTV, 90% (D90%) of HRCTV, and IRCTV for the new design with p-value of 0.008, 0.005 and 0.0018, respectively. Comparing the physical dose of D98% of GTV, D90% of HRCTV, and IRCTV when using the new design, it averagely increased by 11.7%, 8.0%, 19.4%, respectively per fraction. ConclusionsDosimetric comparison revealed the new designs increased the dose to GTV, HRCTV and IRCTV and fulfilled the dose constraints of bladder, rectum and sigmoid. The 3D printed new design is biocompatible, inexpensive and can be patient specific.

Solubility and diffusivity of hydrogen and its isotopes in the BeO system

AbstractThis work revisits hydrogen insertion in the wurtzite beryllium oxide in order to fill the gap in scientific knowledge regarding the diffusion coefficients of the different chemical states of hydrogen (neutral, charged, or molecular). Both first‐principle and macroscopic models were used to this end. In the former, two exchange‐correlation functionals (PBE and SCAN) were used to compute the properties of interest and accuracy was then discussed. Regarding the behavior of interstitial insertion of hydrogen, this work is slightly different from previous works; hydrogen was mainly found in the form of charged H− or H+ ions, depending on experimental conditions. In regard to diffusivity properties, a complex migration pathway was found for hydrogen cation. Finally, the present study succeeded in producing a reliable set of diffusion coefficients for neutral, charged, and molecular hydrogen.

8 Hybrid intracavitary and interstitial brachytherapy for cervical cancer in the outpatient setting

Image-guided hybrid intracavitary and interstitial brachytherapy (HBT) for the treatment of locally advanced cervical cancer may improve outcomes compared to intracavitary brachytherapy alone. Pain control is usually achieved with general anesthesia (GA), which increases both treatment duration and the risk of complications with each treatment. Here we detail the results of our institution's protocol with CT-guided interstitial needle placement, utilizing minimal sedation. A single-institutional database of patients who underwent HBT for cervical cancer from June 2018 to May 2020 was queried. Patterns of anesthesia usage, step-by-step procedural times, medication usage, and treatment-related complications were reviewed. All patients had a Smit sleeve placed in the OR under GA days before their first HBT treatment. Prior to HBT, patients received minimal sedation, composed of oral lorazepam and hydrocodone/acetaminophen. Tandem and ovoids were inserted and interstitial needles were placed under CT guidance. The patients were moved from the CT table to a surgical bed, and then to the radiation vault for treatment delivery. The applicator was then removed and vaginal packing was inserted if any bleeding occurred. A total of 244 implants were placed in 63 patients under minimal sedation. 61 patients (96.8%) tolerated the procedure, 2 (3.2%) required epidural anesthesia, and 0 required transition to GA. The median time for the entire procedure (CT room entry to exit of the HDR room) was 70.0 mins (mean 70.3 mins, range 54–100 mins). The median time for the interstitial needle insertion portion was 9.0 mins (mean 9.8 mins, range 4–24 mins). Bleeding occurred in 54 (22.1%) implants, which resolved after 3 minutes of vaginal packing (mean 3.33 mins, range 1–8 mins). Our outpatient HBT protocol was efficient and well-tolerated, with reasonable bleeding rates which were minimal and quickly resolved. HBT with minimal sedation was achievable at a high percentage (96.8%). The performance of HBT without GA may reduce treatment time, costs, and anesthesia-related adverse effects. Treatment with minimal sedation has the potential to enable more universal use of HBT, improve brachytherapy dosimetry, and enhance patient outcomes. Further investigation is warranted.

GSOR11 Presentation Time: 9:55 AM: 3D Printing Enhanced GYN Brachytherapy: From Novice to Expert in One Print with the TARGIT-FX

<h3>Purpose</h3> It is well established in cervical brachytherapy that the addition of interstitial (IS) needles to intra-cavitary (IC) applicators can significantly enhance dosimetry by improving target coverage without increasing normal tissues doses. Accurate placement of interstitial needles requires significant technical skill and imaging guidance proficiency, thereby limiting the benefits to a subset of practitioners and patients. Available commercial combined IC/IS applicators restrict the available needle positions to often unsatisfactory locations for optimized dosimetry. We have developed and further improved our supplemental templates that attach to the tandem applicator and guides needles to optimized positions for different tumor topologies. This new TARGIT-FX (Tandem Anchored Radially Guiding Interstitial Template - Flexible eXtended) is 3D printed from biologically compatible materials, can be steam sterilized and provides multiple degrees of flexibility to simplify and facilitate interstitial needle insertion. <h3>Materials/Methods</h3> Our previously described IS needle guide (TARGIT), which facilitates placement of complementary needles in a tandem and ovoid implant, was redesigned with the purported goal of added flexibility and ease of use. The tandem attached small template was extended all the way to the vaginal introitus to allow needle insertion from outside the patient. The number of needle position options increased from four to nine to better cover a wider range of clinical situations: three paired width options ((2.0, 1.5 and 1.25 cm width) at the level of point A and three individual posterior locations (figure, insert E). The new design has been used clinically for 14 different patient implants During the procedure, the tandem is first inserted (Figure 1A), the TARGIT-FX is then slid over in position and secured over the tandem (Fig. 1B-C); after the ovoids are placed, needles can be inserted from outside the patient in the selected locations as clinically required (Fig. 1 D). Figure 1E show all the needle potential positions. The procedure time and relevant dosimetric parameters were tracked, as well as usability. <h3>Results</h3> The procedure time with the TARGIT-FX was decreased to 24 min from a benchmark of 29 min with the older TARGIT design (average over 68 implants). The V100% remained similar with 92.2% as compared to the 90.2% TARGIT benchmark, while organs at risk remained within constraints. The main goals of flexibility were achieved as follows: the larger number of needle positions enabled greater customization and live changes during the procedure based on the patient anatomy as visualized on live transrectal ultrasound. The ease of use, in particular the ability to reliably insert and position needles from outside the patient, enabled our medical residents under supervision to confidently perform the entire combined IS/IC implants and even first fraction implants. In addition, the new design enabled in one particular case the addition of a needle after the initial procedure, following the planning CT, as the needle could be inserted from outside with the patient lying on the CT table in scanning position. The reliability and consistency of needle placement with the new design may further increase speed since ultrasound imaging during the procedure may be reduced or omitted. <h3>Conclusion</h3> The 3D printed TARGIT-FX enables simple, fast and reliable interstitial needle insertion for combined tandem and ovoid and IS implants. The flexibility of the design enables new or less experienced users to improve the degrees of freedom and dosimetry of their combined IC/IS implants.

GSOR2 Presentation Time: 9:05 AM: Implementation of Hybrid Intracavitary and Interstitial Brachytherapy for Cervical Cancer in a Freestanding Clinic

<h3>Purpose</h3> Radiation therapy for locally-advanced cervical cancer consists of external beam radiation therapy and brachytherapy. While the recent introduction of image-guided brachytherapy and hybrid intracavitary and interstitial brachytherapy treatments (HBT) may potentially improve clinical outcomes, current literature describes the procedure requiring significant resources (such as general anesthesia, conscious sedation, and MRI-based treatment planning). With increases in treatment time and patient movements, there is greater potential for positional changes of the applicator and neighboring organs at risk (OAR), which can alter dosimetry. Furthermore, these resources might not be universally available to all radiation oncology centers that perform intracavitary cervical brachytherapy, potentially limiting the widespread implementation of HBT. Here we describe our experience with CT-guided interstitial needle placement in a typical freestanding outpatient setting, with an emphasis on minimization of patient movement and treatment duration. <h3>Materials and Methods</h3> All patients that were treated with HBT from June 2018 to May 2020 were included in this series. Initially, patients were taken to the operating room, for an exam under anesthesia and Smit sleeve placement by the radiation oncologist. The patients were determined to need interstitial brachytherapy either by exam under anesthesia, due to anatomy and tumor extent, or after the first brachytherapy treatment, due to dosimetry. All tandem, ovoid and needle insertions and HDR treatments were performed in a freestanding clinic, on the CT simulator table. The patients were treated using minimal sedation (oral lorazepam and oxycodone/acetaminophen). An indwelling urinary catheter was inserted into the bladder. The tandem and ovoids (Elekta) were inserted in the patient, and a vaginal balloon was substituted for packing. Multiple CT scans were performed while advancing the interstitial needles, the bladder was filled with 180 cc of diluted contrast, and a final CT scan was taken for planning purposes. The patients were shifted from the CT table to a surgical bed (single shift), and then transported to the treatment room while treatment planning was performed using Oncentra (Elekta) treatment planning software. After the treatment plan was approved, the bladder was refilled to 180 cc and treatment was delivered using a microSelectron HDR afterloader (Elekta). The applicator was removed and the patient was examined for bleeding. If any vaginal bleeding occurred, vaginal packing was inserted with pressure applied. Time stamps and clinical data were collected during each procedure. <h3>Results</h3> Sixty-three patients underwent placement of a total of 244 interstitial implants. The median time for the entire procedure, from the time of patient entry into the CT simulation room to exit of the HDR treatment room, was 70.0 minutes (mean 70.3, range 54-100). The median time after tandem and ovoid insertion to complete interstitial needle insertion was 9.0 minutes (mean 9.8, range 4-24), using median 2 needles (mean 1.93, range 1-3) and median 3 CT scans (mean 2.63, range 1-4). Bleeding occurred in 22.1% (54/244) of implants, which resolved after median 3 minutes (mean 3.33, range 1-8) of vaginal packing with pressure. All patients (100%) required only one total shift, from the CT table to the mobile surgical bed. <h3>Conclusions</h3> In our series, the interstitial insertion portion of the HBT added 9 minutes, with an overall procedure time of 70 minutes (including insertion, planning, treatment and removal). There was an acceptable bleeding rate which quickly resolved with vaginal packing and pressure. Combining intracavitary and interstitial implants using a hybrid applicator appears to be feasible, efficient and safe in an outpatient freestanding clinic. Further studies aimed at evaluating long-term toxicities and tumor control are warranted.

High-Dose-Rate Interstitial Brachytherapy for Deeply Situated Gynecologic Tumors Guided by Combination of Transrectal and Transabdominal Ultrasonography: A Technical Note.

Background and PurposeHigh-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US).Material and MethodsNine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US.ResultsThere were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs.ConclusionsIn brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

A novel intra pre-plan method of interstitial needle optimization for cervical cancer patients treated with Venezia applicator brachytherapy: a technical note.

PurposeNovel hybrid Venezia applicator enables intracavitary and interstitial brachytherapy (BT) for locally advanced cervical cancer. However, the method to determine the optimal interstitial needle number, position, and depth using this applicator is unknown. Therefore, we aimed to establish a method for reliable needle optimization.Material and methodsWe produced a template model of the Venezia applicator with whole needles, and acquired computed tomography (CT) images (template CT). Using this template CT as a map, clinicians could define interstitial needle’s insertion route in advance. During treatment, we first placed tandem and ovoid, and acquired a CT (tandem + ovoid CT). This was fused to the template CT by matching the contour of applicators with high accuracy. Then, we determined the optimal interstitial needle number, position, and depth to fit high-risk clinical target volume (HR-CTV) and avoid organs at risk (OARs) on the fused CT (intra pre-plan). Next, we re-inserted the tandem and ovoids with interstitial needle into patient’s uterus and vagina. We inserted the optimized interstitial needle using insertion tool of optimal depth immediately following the applicator insertion. Lastly, a real-time treatment planning CT was performed, followed by planning and treatment.ResultsWe achieved a good dose distribution of Venezia applicator BT using intra pre-plan method to optimize the number of interstitial needles, position, and depth.ConclusionsThis novel intra pre-plan method of interstitial needle optimization using template CT fusion provides high reproducibility, efficiency, and safety for patients with cervical cancer treated with brachytherapy using Venezia applicator.

PHSOR03 Presentation Time: 10:10 AM: Practical Needle Placement and Dosimetry Improvements with Hybrid Intracavitary/Interstitial Ring Applicators

Purpose: Hybrid intracavitary/interstitial (IC/IS) applicators have been shown to improve local control for HRCTV > 30cc and dosimetry in all volume HRCTV compared to traditional intracavitary (IC) cervical HDR brachytherapy. Standard needle insertion patterns have not been well-established for hybrid IC/IS applicators. We quantify dosimetric benefits of the Vienna-style IC/IS applicator compared to IC-alone and aim to establish standard interstitial needle-loading and insertion depth patterns for non-bulky HRCTV.

Practical needle selection for Vienna-style applicators: improving therapeutic ratio in hybrid intracavitary-interstitial brachytherapy.

PurposeHybrid intracavitary and interstitial (IC/IS) applicators improve dose distribution compared to traditional IC applicators in cervical high-dose-rate (HDR) brachytherapy. There is a learning curve to these applicators, and initial standard needle insertion patterns have not been well-established. In this study, we quantified dosimetric benefits of IC/IS applicators, and offer practical initial interstitial needle-selection, insertion depths, and dwell position recommendations.Material and methodsFifteen patients previously treated with a tandem and ring IC applicator and magnetic resonance (MR)-guidance were re-planned at first fraction using a digital template of Vienna-style interstitial needles. IC/IS plans maintained identical high-risk clinical target volume (HR-CTV) D90% while reducing dose to organs at risk (OARs). To assess the validity of planning using virtual needles, virtual needle templates were overlaid on twelve clinical IC/IS plans, and the displacements between 40 physical and virtual needles were measured at 3 cm depth.ResultsThe median HR-CTV volume in the present study was 19.6 cc (range, 6.6-60.5 cc). HR-CTV D90% was maintained in all re-plans. Median bladder D2cc decreased from 5.4 Gy per fraction to 4.8 Gy (p = 0.003); median rectum D2cc decreased from 2.4 Gy per fraction to 2.0 Gy (p = 0.007). We suggest that a standard loading pattern should include needles in lateral channels 4, 5, and 9, 10 inserted 3 cm deep, with dwell times < 20% of the combined tandem and ring dwells. The mean displacement between planned and physical needles was 1.8 mm. All needles but three deviated less than 3.3 mm, demonstrating the validity of re-planning with virtual needles.ConclusionsHybrid IC/IS applicators maintain excellent D90% coverage while improving dose to OARs compared to IC-only applicators, even in non-bulky HR-CTVs. We offer practical recommendations for needle selection, insertion depth, and relative weighting for Vienna-style applicators in small HR-CTVs. These results support previous publications, offering practical recommendations for users of Vienna-style hybrid applicators.

Integrated Intraoperative MRI-Guided Brachytherapy for Cervical Cancer: An Institutional Experience of Treatment Workflow, Planning and Patient Toxicities

MRI planning for cervical cancer brachytherapy is associated with reduced toxicity and improved outcomes compared to historical techniques. MRI brachytherapy, however, is resource-intensive, which poses challenges in workflow and efficiency. Currently, most MRI planning protocols involve performing the brachytherapy insertion followed by patient recovery before obtaining MRI images with the patient awake. As this conventional process is lengthy and can cause patient discomfort, the goal of this study is to report the experience of an integrated MRI-based intraoperative brachytherapy program. Patients undergoing intraoperative MRI-guided brachytherapy for cervical cancer from an institutional registry trial between 2018 and 2019 were reviewed. All had intracavitary and/or interstitial brachytherapy insertion, MRI-imaging /planning, treatment delivery and applicator removal all under general anesthesia (GA). Patient, cancer and treatment-related data were abstracted. Brachytherapy specific data included applicator characteristics, dose aims, target prescriptions and organs-at-risk (OAR) doses. Pain was scored using a Likert scale from 1-10 at recovery, and at scheduled times prior to discharge. Procedure and anesthetic related toxicities at recovery and first follow-up were reviewed. Thirty-four patients with stage IBI - IIIA cervical cancers were available for analysis in this novel intraoperative program. Median age was 62 (range, 31 - 80). Eighteen patients were treated with interstitial needles for at least 1 insertion (15 hybrid, 3 perineal). The median number of needles used for fractions (Fx) 1, 2, 3 and 4 were 4, 5, 4 and 4 for hybrid applicators and 21, 21, 20 for perineal templates (3 fractions) respectively. For interstitial patients, average times for insertion (Ins), MRI imaging (MRI), planning/treatment (PlanTx) were respectively 61 +/- 14 mins, 42 +/- 8 mins, 98 +/-24 mins. Total treatment time under GA was 200 +/- 35 mins. For intracavitary patients, Ins, MRI, PlanTx times were respectively 52 +/- 14 mins, 40 +/- 10 mins, 80 +/- 17 mins, with total treatment time under GA being 172 +/- 25 mins. Mean CTVHR D90, rectum D2cc and bladder D2cc doses were 93.7.1 Gy (80.2 - 111.1), 57.9 Gy (49.7 - 67.9) and 74.9 Gy (58.7 - 86.2) respectively. There were no observed anesthetic complications, and all patients were discharged the same day. Mean pain scores post-anesthesia for interstitial patients were 0.75 (0-2), 0.95 (0 - 3.75), 0.9 (0 - 4.62) and 2.3 (0-5.4) for each consecutive fraction. For intracavitary mean pain was 0.81 (0 - 4.5), 0.59 (0 - 3.3), 0.48 (0 - 4.4) and 0.94 (0 - 4). Intraoperative MRI-based brachytherapy planning and treatment is feasible and well-tolerated with minimal pain. Interstitial procedures tended to be longer than intracavitary, but no anesthetic complications were seen. Prospective evaluation of patient toxicities, outcomes and experience is needed to evaluate this technique further.

Intraoperative MR-adaptive Interstitial HDR Brachytherapy for Advanced Gynecological Cancers

MR-adaptive interstitial brachytherapy uses MRI imaging (+/- CT) after each needle insertion to provide treatment plan adaptation and customization. Our previous interstitial workflow involved recovery from general anaesthesia (GA) with needles in place, with patients in discomfort for >36 hrs during MRI/CT imaging, treatment planning, treatment and needle removal. In addition, patients were admitted overnight to allow for two HDR treatments for each interstitial insertion, causing further distress and pain. Here, we describe a solely MRI-based workflow, which allows our multi-disciplinary team to provide intraoperative MR-adaptive interstitial HDR brachytherapy to our patients with advanced gynecological cancer on an outpatient basis.

Interstitial versus substitutional metal insertion in V2O5 as post-lithium ion battery cathode: a comparative GGA/GGA + U study with localized bases

The generalized gradient approximation (GGA) often fails to correctly describe the electronic structure and thermochemistry of transition metal oxides and is commonly improved using an inexpensive correction term with a scaling parameter U. The authors tune U to reproduce experimental vanadium oxide redox energetics with a localized basis and a GGA functional. The value for U is found to be significantly lower than what is generally reported with plane-wave bases, with the uncorrected GGA results being already in reasonable agreement with experiments. This computational set-up is used to calculate interstitial and substitutional insertion energies of main group metals in vanadium pentoxide and interstitial doping is found to be thermodynamically favored.

Feasibility of Multiple Outpatient Interstitial Insertions Using a Hybrid Intercavitary and Interstitial Applicator for Cervical Cancer in a Freestanding Clinic

Radiation therapy for locally advanced cervical cancer consists of external beam radiation therapy and brachytherapy. Recent introduction of image guided brachytherapy and combination intercavitary and interstitial applicators can potentially improve outcomes. Here we describe our experience with CT guided interstitial needle placement in a freestanding outpatient setting. All patients that were treated with both intercavitary and interstitial brachytherapy from June 2018 to January 2019 were included in this series. Initially, patients were taken to the operating room, for an exam under anesthesia and smit sleeve placement by the radiation oncologist. The patients were determined to need interstitial brachytherapy either by exam under anesthesia, due to anatomy, or after the first brachytherapy treatment, due to dosimetry. All tandem, ovoid and needle insertions, and HDR treatments were done in a freestanding clinic. The patients were pre-medicated with oral medication. Initially, an indwelling urinary catheter was inserted into the bladder. The tandem and ovoids were inserted the patient, and a vaginal balloon in lieu of packing. Multiple CT scans were done while advancing the interstitial needles. A final CT scan for planning was done after filling the bladder with 180 cc of diluted contrast. The patients were moved to the treatment room while treatment planning was being done, using treatment planning. After the treatment plan was approved, the bladder was refilled to 180 cc and treatment was delivered using a HDR afterloader. The applicator was removed and the patient was examined for bleeding. If any vaginal bleeding occurred, vaginal packing was inserted and pressure held. Time stamps and clinical data was collected during each procedure. 32 implants on 9 patients was performed. The median time after tandem and ovoid insertion to complete interstitial needle insertion was 10 min (mean 10, range 6-24 min), using median 3 (mean 2.75, range 1-4) CT scans and median 2 (mean 1.75, range 1-3) needles. The overall time from the initiation of the procedure to removal of the applicator and any vaginal packing was median 72 min (mean 73 min, range 61 min to 100 min). Bleeding occurred in 25% of patient, which resolved after median 3 (mean 3.38, range 1-8) minutes of vagina packing with pressure. No patients were admitted for vaginal bleeding. No patient was unable to complete her prescribed treatment due to pain or discomfort. The interstitial insertion added 10 minutes with an overall procedure time of 72 min (including insertion, planning, treatment and removal), with a 25% bleeding rate which resolves with an average of 3 min of vaginal packing and pressure. Combining intracavitary and interstitial implants using a hybrid applicator seem to be feasible, efficient, and safe in an outpatient freestanding clinic. Further study with long term toxicity data and tumor control data is warranted.

Investigation on the structural and microstructural properties of copper-doped hydroxyapatite coatings deposited using solution precursor plasma spraying

Structural and microstructural investigation of solution precursor plasma sprayed copper-doped hydroxyapatite coatings with different Cu dopant concentration was carried out. Scanning electron micrographs did not show any significant morphological changes at the surface and cross-section of the coatings as copper content increases. X-ray diffraction results showed the decrease in the HA phase content from 93 wt.% to 14 wt.% and its degree of crystallinity from 94% to 85% with increasing copper concentration. Raman and IR spectra revealed the broadening and red-shifting of the phosphate bands due to the distortion of the HA structure caused by possible insertion of copper. X-ray photoelectron spectroscopy identified Cu and Cu2+ as copper species incorporated in HA. Rietveld refinement showed an increase in the lattice a and c parameter and expansion of the unit cell volume associated to an interstitial insertion of Cu along the hexagonal channel of the HA structure.

A 105\xa0kb interstitial insertion in the Xq27.1 palindrome from pseudoautosomal region PAR1 causes a novel X-linked recessive compound phenotype

BackgroundGenomic disorders present a wide spectrum of unrelated clinical entities that result from genomic rearrangements. Interstitial insertions requiring three points of breakage are rare genomic rearrangement events. The pseudoautosomal region PAR1, homologous between the Xp22 and Yp11 loci, has a high crossover and recombination rate. A 180 bp human-specific palindrome at Xq27.1 appears to be a hotspot for genomic rearrangement, and several genetic diseases/phenotypes associated with Xq27.1 palindrome-driven genomic rearrangement have been reported. Here we investigate a Chinese family with an extremely rare X-linked compound phenotype that remains undiagnosed. We attempt to identify underlying genetic causes by an integrated genome analysis.MethodsA five-generation Chinese family with a distinct X-linked compound phenotype was recruited. Peripheral blood samples were collected and genomic DNA was extracted. Systemic physical and lab examinations were performed to evaluate the phenotype. An integrated genomic analysis was performed. Genotyping and linkage analysis were conducted to map the disease locus. Whole exome sequencing was performed to detect mutations in coding region. Whole genome sequencing was used to detect single nucleotide variations, small insertions, small deletions, or large structural variations. Copy number variation scanning was also performed on the genome scale. Interstitial insertion was confirmed by gap-PCR and quantitative-PCR, and breakpoint junctions were identified by genome walking and direct sequencing. Expression of products of genes nearby to the Xq27.1 palindrome was measured in peripheral blood from patients and unrelated controls via quantitative-PCR.ResultsThe identified compound phenotype of genu varum, cubitus valgus, and everted lipsdoes not match any reported clinical entities. Fine mapping and linkage analysis identified a candidate interval of 4 Mb on the X chromosome. No potential coding region mutations were detected. A 105 kb genomic fragment of PAR1 containing no coding genes was duplicated and inserted into the center of a human-specific palindrome at Xq27.1. The interstitial insertion fully cosegregated with the family phenotype. No expression of FGF13 or SOX3 was detected in peripheral blood from the proband or unrelated controls.ConclusionWe report an extremely rare phenotype associated with an infrequently-seen genomic rearrangement. The novel compound phenotype is X-linked and characterized by genu varum, cubitus valgus, and everted lips. A 105 kb interstitial insertion of a PAR1 fragment into the Xq27.1 palindrome is associated with the phenotype in the family. The present study identified the underlying genetic cause of the phenotype, expanding the spectrum of known human-specific Xq27.1 palindrome insertion events and associated phenotypes.

Substitutional and interstitial impurity p-type doping of thermoelectric Mg2Si: a theoretical study

ABSTRACT The narrow-gap magnesium silicide semiconductor Mg2Si is a promising mid-temperature (600–900 K) thermoelectric material. It intrinsically possesses n-type conductivity, and n-type dopants are generally used for improving its thermoelectric performance; however, the synthesis of p-type Mg2Si is relatively difficult. In this work, the hole doping of Mg2Si with various impurity atoms is investigated by performing first principles calculations. It is found that the Ag-doped systems exhibit comparable formation energies ΔE calculated for different impurity sites (Mg, Si, and interstitial 4b ones), which may explain the experimental instability of their p-type conductivity. A similar phenomenon is observed for the systems incorporating alkali metals (Li, Na, and K) since their ΔE values determined for Mg (p-type) and 4b (n-type) sites are very close. Among boron group elements (Ga and B), Ga is found to be favorable for hole doping because it exhibits relatively small ΔE values for Si (p-type) sites. Furthermore, the interstitial insertion of Cl and F atoms into the crystal lattice leads to hole doping because of their high electronegativity.

Electronic structure, defect properties, and hydrogen storage capacity of 2H-WS2: A first-principles study

First-principles calculations based on density functional theory (DFT) have been performed for layered 2H tungsten disulphide (WS2) with the aim to find its possible applications in opto-electronic and hydrogen storage devices. To study opto-electronic features of WS2, we solve the Bethe-Salpeter-Equation (BSE) on top of the standard self consistent GW quasiparticle (QP) calculations. These calculations capture the excitonic effects which originate near the edge of conduction band, shows good agreement with the available measured data. The suitability of WS2 as a prospective material for hydrogen storage were predicted by using the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional. We have explored the effect of interstitial hydrogen and H2 molecules insertion on the structural stability of WS2 in detail. The hydrogen atom charge states dependent stability was studied in the context of formation energy. Our calculations suggest that interstitial hydrogen can act as a deep donor whereas H2 molecule exhibits more stability. The diffusion energy of H2 molecule from one hollow site to the nearest in-plane hollow site has been calculated using transition state theory. Finally, ab−initio molecular-dynamics (AIMD) calculations are carried out for WS2 consisting of 16H2 molecules that ensures its structural stability at temperatures 300, 500, and 1000 K. Present predictions show that this material may be utilize for hydrogen storage due to expected high hydrogen density.

Structural effects in the interstitial solid solution system (La,Ce)(Fe,Si)13Cx-H: Correlation with hydrogenation kinetics

Steady state and in-situ neutron powder diffraction on selected compositions of the magneto-caloric (La,Ce)(Fe,Si)13CxHy compounds has been used to locate the sites accommodated by the interstitial species and to reveal the structural modifications (breathing) that occur upon metal substitution and/or interstitial insertion. The latter type of measurement in which the sequential filling of interstitial sites is followed allows one to extract some useful hydrogenation kinetics data. This structural investigation has allowed to precise the deformations undergone by the complex metallic alloys La(Fe,Si)13 when subjected to light interstitial insertion or rare earth substitution at the cation site of the NaZn13-structure type. We attempt to correlate hydrogenation kinetics variations (depression or enhancement of the hydrogen absorption rate) with a particular inhomogeneous cell variation (breathing) and bonding of the NaZn13 structure-type.