Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Efficient continuous-wave Nd:YVO4/KGW intracavity Raman laser.

We demonstrate an efficient Nd:YVO4/KGW intracavity Raman laser in continuous-wave (CW) scheme. With a V-shaped fundamental laser cavity and a short Stokes cavity in it, the oscillating beam sizes are designed to alleviate the thermal effect and to enhance the Raman gain for efficient CW operation. The output power of CW Stokes wave at 1177 nm reached 9.33 W under an incident laser diode pump power of 36.65 W, with corresponding optical efficiency being 25.5%. To the best of our knowledge, these are the highest Stokes output power and conversion efficiency of CW intracavity Raman lasers.

1.2†W single-frequency Tm3+/Ho3+ co-doped fiber oscillator at 2050†nm.

In this Letter, a watt-level single-frequency fiber oscillator at 2050 nm was demonstrated for the first time, to the best of our knowlegde, in a linear laser cavity with a piece of an un-pumped Tm3+/Ho3+ co-doped fiber serving as a saturable absorber. With delicate optimization of mode filtering effect of the dynamic gratings formed in the saturable absorber, a maximum single-frequency laser output power of 1.2 W was achieved under a total bidirectional pump power of 5.8 W at 1570 nm, and the corresponding optical efficiency is 20.7%. This is, to the best of our knowledge, the highest power of a single-frequency fiber oscillator at the wavelength above 2 µm.

Widely tunable single-frequency Er-doped ZBLAN fiber laser with emission from 3.37 to 3.72†µm.

We demonstrate a widely tunable single-frequency Er-doped ZBLAN fiber laser operating on a 4F9/2→4I9/2 transition band. An uncoated germanium (Ge) plate serves as a narrow-bandwidth etalon and is inserted in the cavity to achieve a single longitudinal mode selection. Wavelength tuning from 3373.8 nm to 3718.5 nm was demonstrated by using a blazed diffraction grating at 3.5 µm. At the emission peak of 3465.6 nm, the laser yields over 100 mW single-frequency output power, with a 3 dB linewidth <6.9 MHz, and a slope efficiency (with respect to the incident 1990 nm pump power) of 20.3%. Such a tunable mid-infrared single-frequency fiber laser may serve as a versatile laser source in spectroscopy and sensing applications.

High-power, high-efficiency single-frequency DBR fiber laser at 1064†nm based on Yb3+-doped silica fiber.

A high-power, high-efficiency single-frequency fiber laser at 1064 nm was demonstrated based on a distributed Bragg reflector (DBR) all-silica-fiber configuration. A single-frequency laser with an output power of 642 mW and slope efficiency of 66.4% with respect to absorbed pump power was achieved from a 1.2-cm-long commercially available Yb3+-doped silica fiber. To the best of our knowledge, this is the highest single-frequency laser power and efficiency obtained from the DBR all-silica fiber laser. The work presented here paves the way for the development of high-power, robust, and cost-effective single-frequency Yb3+-doped all-silica fiber lasers.

The effect of neutrophil extracellular traps in venous thrombosis.

Neutrophil extracellular traps (NETs) as special release products of neutrophils have received extensive attention. They are composed of decondensed chromatin and coated with nucleoproteins, including histones and some granulosa proteins. NETs can form a network structure to effectively capture and eliminate pathogens and prevent their spread. Not only that, recent studies have shown that NETs also play an important role in venous thrombosis. This review provides the most important updated evidence regarding the mechanism of NETs formation and the role of NETs in the process of venous thrombosis. The potential prophylactic and therapeutic value of NETs in venous thrombotic disease will also be discussed.

Single knotless-anchor with two ethicon 2# for Ellman grade III bursal-side partial thickness rotator cuff tears: a cadaveric biomechanical study and short-term clinical evaluation.

BACKGROUND: Several surgical techniques are used to treat bursal-side partial thickness rotator cuff tears (PTRCTs). However, use of single knotless-anchor with two Ethicon 2# repair technique for PTRCTs has not been reported. MATERIALS AND METHODS: Bursal-side PTRCTs (Ellman grade III, 75% thickness of tears) were created in the supraspinatus tendon in 16 fresh-frozen cadaveric shoulders. The specimens were randomly assigned to two equal groups: (1) Group A (Transtendon repair), a single knotless-anchor repair with two Ethicon 2#; (2) Group B, Conversion repair (Double-row, DR). Post-repair, each specimen was subjected to cyclic loading test from 5 to 100 N (50 cycles), followed by an ultimate failure test. The displacement of greater tuberosity (mm) and ultimate (N) were recorded. In the clinical study, 12 patients diagnosed with Ellman grade III Bursal-side PTRCTs (using a single knotless anchor with two Ethicon 2# repair techniques) were operated on and analyzed. Visual analog scale (VAS), American Shoulder and Elbow Surgeons Score (ASES), Constant-Murley Score (CMS), and range of motion (ROM) were assessed before surgery and at final minimum follow-up (>1year). RESULTS: There was no significant between-group difference with respect to load-to-failure test (Group A, 359.25 ± 17.91 N; Group B, 374.38 ± 13.75 N, P > 0.05). There were no significant differences with respect to rotator cuff displacement of 10 mm (Group A, 190.50 ± 8.52 N; Group B, 197.25 ± 6.84 N, P > 0.05) and 15 mm (Group A, 282.25 ± 12.20 N; Group B, 291.13 ± 14.74 N, P > 0.05). However, there was significant between-group difference with respect to displacement of 3 and 5 mm (P < 0.05). In the clinical trial, all patients were followed up for an average of 20.4 months (12-29 months). At the last follow-up after surgery(minimum>1year), the VAS score was 0.50 ± 0.67 (0-2), the ASES score was 86.50 ± 3.96 (79-92), the CMS score was 85.08 ± 5.65 (74-93), the mean Forward flexion ROM was 154.00°± 12.48° (131°-169°), and the abduction ROM was 165.00°±13.26° (138°-173°). There was a statistically significant difference between the results of the preoperative and the last postoperative follow-up. The results of the last postoperative follow-up were statistically different from those of the preoperative follow-up (P < 0.05). Regarding complications, stiffness (2 cases) and shoulder impingement (1 case) occurred in 3 cases (25%). CONCLUSION: A single knotless anchor with two Ethicon 2# may provide a biomechanically and clinically feasible option for the treatment of bursal-side Ellman grade III PTRCTs, particularly in resource-constrained settings. MESH KEYWORDS: Bursal-side Ellman Grade III; Single Knotless-anchor; Double-row repair; Biomechanical study; Short-term clinical evaluation.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy versus Sorafenib for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Randomized Trial.

Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.

High-energy single-frequency pulsed fiber MOPA at 1064†nm based on a hybrid active-fiber.

We report a single-frequency pulsed Yb-doped fiber master-oscillator-power-amplifier at 1064 nm producing output with pulse energy of 0.6 mJ for a pulse width of 95 ns at a pulse repetition frequency of 5 kHz. Integral to this laser design was the application of a hybrid active-fiber, which integrated a length of heavily Yb-doped phosphosilicate fiber (with a core diameter of 50 µm) with a silica gain fiber (with core diameter of 35 µm). This was used in the power amplifier stage to both suppress stimulated Brillouin scattering and to enhance the gain saturation for improved efficiency and spectral signal to noise ratio. The seed pulses were pre-shaped so that sawtooth-like pulses were obtained after amplification, this having the effect of preventing linewidth broadening induced by self-phase modulation. A spectral linewidth of ∼15 MHz was measured at the maximum peak power of 6.3 kW.

Single-frequency fiber laser at 880†nm.

Single-frequency fiber lasers with extremely low noise and narrow spectral linewidth have found many scientific and practical applications. There is great interest in developing single-frequency fiber lasers at new wavelengths. In this paper, we report a single-frequency Nd3+-doped phosphate fiber laser operating at 880 nm, which is the shortest demonstrated wavelength for a single-frequency fiber laser thus far, to the best of our knowledge. An output power of 44.5 mW and a slope efficiency of 20.4% with respect to the absorbed pump power were obtained with a 2.5-cm-long 1 wt.% Nd3+-doped phosphate fiber. Our simulation results show that higher single-frequency laser output can be achieved with 1.5 wt.% or 2 wt.% Nd3+-doped phosphate fiber with mitigated ion clustering.

Erbium-doped ZBLAN fiber laser pumped at 1.7 µm for emission at 2.8 µm.

In this paper, a novel, to the best of our knowledge, efficient pump scheme for an erbium-doped fluoride fiber laser with emission at 2.8 µm in the mid-infrared region is proposed and demonstrated. A singular pump source at 1.7 µm is used to excite Er3+ ions from ground state 4I15/2 to lower laser level 4I13/2, and then further boost the ions to 4I9/2, where a non-radiation transition occurs for the Er3+ ions to reach upper laser level 4I11/2. This scheme can efficiently recycle ions on the lower laser level 4I13/2 by excited-state absorption, therefore realizing population inversion and enhancing laser efficiency. In our demonstration, a 660-mW laser output at 2.8 µm is achieved from a 1.7-µm core-pumped erbium-doped fluoride fiber laser, where the slope efficiency versus launched pump power is 23.7%. The proposed innovative pump scheme shows great potential to realize high-power, high-efficiency erbium-doped fiber lasers at 2.8 µm.

Single-frequency Tm-doped fiber laser with 215†mW at 2.05 µm based on a Tm/Ho-codoped fiber saturable absorber.

We demonstrate an efficient single-frequency Tm-doped fiber laser at 2050 nm. A ring cavity scheme is employed to boost the net gain at the wavelength. A piece of Tm/Ho-codoped fiber with an absorption coefficient at 2050 nm higher than that of a Tm-doped fiber is used to establish the dynamic Bragg grating for enhancing the frequency selection capability. A single-frequency output of 215 mW is obtained under 2 W of 1570-nm pump power, with the slope efficiency being 22%. To the best of our knowledge, this is the highest single-frequency all-fiber laser oscillator output power above 2 µm.

Diode-pumped 1.15 W linearly polarized single-frequency Yb3+-doped phosphate fiber laser.

Compact and robust high-power single-frequency laser oscillators are in great demand for some specific applications where narrow-linewidth lasers with extremely low noise are required. In this paper, we report a single-mode-diode-pumped watt-level single-frequency Yb3+-doped phosphate fiber laser at 1050 nm based on an all-fiber distributed Bragg reflector cavity. A maximum output power of 1.15 W with a slope efficiency of 66% was achieved with 18-mm-long 8 wt.% Yb3+-doped phosphate fiber. Stable, single-longitudinal-mode lasing with a spectral linewidth of 9.6 kHz and polarization extinction ratio of ∼30 dB was obtained.

Outcomes from Osteochondral Autograft Transplant or Mosaicplasty in 26 Patients with Type V Osteochondral Lesions of the Talus.

BACKGROUND Mosaicplasty osteochondral transplantation (MOT) has been proved a feasible choice for the treatment of talus osteochondral injury. It can reduce ankle pain and allow performance of daily living activities and elementary sports. However, there are very little data on the restoration of normal life with large lesions. Our investigation focused on assessing outcomes in patients with large lesions. MATERIAL AND METHODS The MOT operation was used, and the donor site was located at the lateral condyle of the femur. Clinical evaluation included the Berndt and Harty outcome question, Visual Analog Scale (VAS) pain score (during rest, walking and running), American Orthopedic Foot and ankle Association (AOFAS) score, International Knee Documentation Committee (IKDC) subjective knee evaluation form, and the Short Form 36 (SF-36). Twenty-four months after surgery, the graft binding was assessed by MRI using the magnetic resonance observation of cartilage repair tissue (MOCART) score. RESULTS We assessed 26 patients, including 14 males and 12 females. The average follow-up time was 33.9±5.2 months. The average lesion size was 173.1±23.5 mm². The average VAS score during rest improved from 4.62±0.85 preoperatively to 1.08±0.27 postoperatively (P<0.05), the score during walking improved from 5.19±0.63 preoperatively to 1.15±0.37 postoperatively (P<0.05), and the score during running improved from 6.08±0.74 preoperatively to 1.39±0.57 postoperatively (P<0.05). The average postoperative AOFAS ankle score improved to 91.5±2.6 (range, 88 to 96), compared with preoperative 75.0±2.8 (range, 70 to 79) (P<0.05). Two patients developed pain in the donor site of the knee joint, and both of them had 2 or more osteochondral plugs harvested. The postoperative SF-36 score increased to 92.2±2.4 (P<0.05). In the last follow-up, 18 patients answered the Berndt and Harty outcome question, all with "good" as the result. CONCLUSIONS MOT is a feasible choice for patients with larger lesions. It can improve the VAS/AOFAS/IKDC/SF-36 scores, and has high patient satisfaction. Graft incorporation helps improve patient quality of life. Our results indicate that a larger osteochondral plug area increases the risk of developing knee donor site pain.

Power scaling and spectral linewidth suppression of hybrid Brillouin/thulium fiber laser.

In this paper, an ultra-narrow linewidth hybrid Brillouin/thulium fiber laser (BTFL) was demonstrated. By optimizing the output coupling, pump scheme, fiber length and Brillouin pump power for the linewidth narrowing, 344-mW output power with a narrow linewidth of 0.93 kHz was obtained from the BTFL, in which the linewidth of Stokes light was suppressed more than 43 times compared with the 40 kHz linewidth of the Brillouin pump. Besides, the influences of output coupling and pump scheme on the power and linewidth behavior of a single-frequency BTFL were also experimentally investigated, and there exists a performance balance among linewidth narrowing, output power and SBS threshold. The output coupling exerted a significant influence on the BTFL performance.

Efficient multi-watt 1720 nm ring-cavity Tm-doped fiber laser.

Using commercial Tm-doped silica fiber and 1570-nm in-band pump source, we demonstrated an efficient 1720-nm all-fiber laser with ring-cavity configuration. The theoretical model based on rate equations was built up to analyze the laser performance of Tm-doped fiber, which exhibits strong absorption in the 1.7-µm region. The results show that efficient laser operation can be achieved through the optimization of output coupling and the length of Tm-doped fiber. An experimental investigation was performed and agreed with the calculation. By using homemade couplers, we experimentally achieved 2.36-W laser output at 1720 nm under a 6-W launched pump. The slope efficiency with respect to the absorbed pump power and optical efficiency were 50.2% and 39.3%, respectively. Due to the employment of a ring resonator, a narrow laser linewidth of ∼4 GHz at maximum output power was observed.

Classification of the subtalar articular surface and its matching situation: an anatomical study on Chinese subtalar joint.

PURPOSE: The subtalar joint (STJ) is complex in anatomy and function. The purpose of this study is to classify the articular surface of the calcaneus in a sample Chinese population and discuss the relationship between its matching situation and the stability of STJ. METHODS: 328 patients with 445 STJs were measured and classified using CT three-dimensional reconstruction. The calcaneal facets were classified according to the morphological characteristics. According to the number, shape, and fusion of the calcaneus and talus facets, the matching situation was determined. The parameters of measurement: the Gissane's angle, the Böhler's angle, the long-axis sum and the short-axis sum, and the average total joint facet area. RESULTS: The calcaneal surfaces in a sample Chinese population were classified into five types: Type I (219, 49.2%), Type II (102, 22.9%), Type III (68, 15.3%), Type IV (47, 10.6%) and Type V (9, 2%). The total matching rate of STJ is 98%. In terms of Gissane's angle, there was a significant difference between Type II and Type IV (P < 0.05). The long-axis sum of Type III (4.53 ± 0.58 cm) was significantly smaller than other types (P < 0.05). Type II (3.64 ± 0.47 cm) was statistically larger than other types in the short-axis sum (P < 0.05). The average total joint facet area of Type III (7.05 ± 1.40 cm2) was significantly smaller than other types (P < 0.05). Type V (9.31 ± 3.96 cm2) was statistical differences with Type II, Type III and Type IV (P < 0.05). There was no statistically significant difference between left and right sides of the articular facets in this study (P > 0.05). CONCLUSIONS: According to Bunnins's classification, the type with separated facets predominated but the matching situation between STJ was not elaborated, which was closely linked to the stability of STJ and surgical strategy of calcaneus fracture. The calcaneus articular surfaces in a sample Chinese population were divided into five types. Type I was the most common type and Type V was the rarest. Type II have the highest stability, Type V may be the lowest stability and Type III was more prone to osteoarthritis. The STJ articular surfaces were basically matched, contributing to the coordinate movement of the STJ. The matching articular surfaces of STJ were more stable than the mismatching surfaces. To some extent that STJ facet number, shape, facet area, and matching situation are factors in STJ stability, and the anatomical variations of the STJ offer predictive value in determining the predisposition to STI.

Effects of Cervical Rotatory Manipulation on Internal Carotid Artery in Hemodynamics Using an Animal Model of Carotid Atherosclerosis: A Safety Study.

BACKGROUND Spinal manipulation, particularly in cervical rotatory manipulation (CRM), has become increasingly popular in physical therapies, with satisfying effect. However, it is still unclear whether CRM affects internal carotid arteries (ICA) with mild carotid atherosclerosis (CAS), especially in hemodynamics. MATERIAL AND METHODS Nine cynomolgus monkeys were randomly divided into 3 groups: the CAS-CRM, the CAS, and the blank control groups. CAS models were developed in the left ICA in the CAS-CRM and the CAS groups. The monkeys in the CAS-CRM group underwent CRM intervention for 3 weeks. Histology and hemodynamics were measured, including peak systolic velocity (PSV), end-diastolic velocity (EDV), time average velocity (TAV), resistance index (RI), and pulsatility index (PI). Measurements were made separately at 3 different rotation angles (0°, 45°, and 90°). RESULTS In the 3 groups, with the increase of rotation angle, the decreasing tendency of PSV, EDV, and TAV and the increasing tendency of RI and PI were statistically significant. At each angle, the monkeys in the CAS-CRM and the CAS groups had lower levels of PSV, EDV, and TAV and higher levels of RI and PI compared with the blank control group. No significant difference in hemodynamics was found between the CAS-CRM and the CAS groups. CONCLUSIONS Both the rotational angle and the atherosclerotic disease can affect the blood flow of the ICA. However, CRM does not cause adverse effects on hemodynamics in cynomolgus monkeys with mild CAS, and appears to be a relatively safe technique.

Implications of Classification of Os Trigonum: A Study Based on Computed Tomography Three-Dimensional Imaging.

BACKGROUND The os trigonum is an accessory bone that is not fully fused with the talus during secondary ossification, and is one of the risk factors of posterior malleolus impact syndrome. The purpose of this study was to classify the os trigonum and to guide the diagnosis and treatment of related clinical diseases. MATERIAL AND METHODS Ankle computed tomography (CT) scans of 586 Chinese patients between October 2014 and October 2018 were reviewed. CT images of 1011 ankle joints were reconstructed to evaluate the classification of the os trigonum and the measurement of anatomical parameters. RESULTS The incidences of os trigonum in 3 groups were determined as type I (1.9%), type II (10.5%), and type III (14.7%). The macro-axis of type II (0.89±0.31) cm was significantly larger than with type I (0.65±0.24 cm) and type III (0.74±0.23 cm) (p<0.05).The minor axis of similar of type I (0.41±0.23 cm) was significantly shorter than that of type II (0.58±0.32 cm) and type III (0.55±0.16 cm) (p<0.05).The distance from os trigonum to calcaneal tubercle was significantly different than that of type I (1.33±0.52 cm), type II (1.67±0.55 cm), and type III (1.84±0.45 cm) (p<0.05). CONCLUSIONS This study showed that os trigonum has a high incidence. Type I was the least common, the volume of type II was larger, and type III was more common. The anatomical parameters of each type may improve treatment of related diseases and the further development of ankle arthroscopic surgery.