Mach-Zehnder Type Annealed Proton Exchange Waveguide and Coplanar Waveguide Modulation Electrode LiNbO_3 Intensity Modulator

The characteristics of a conventional LiNbO3 intensity modulator made up of a Mach-Zehnder(MZ) type annealed proton exchange(APE) waveguide and coplanar waveguide(CPW) modulation electrode are presented. The APE waveguide characteristics and their relations with process parameters are analyzed. At the same time, the electrical characteristics of modulation electrode, such as modulation voltage, microwave effective index associated with modulation bandwidth, characteristics impedance, are also investigated in detail.

Measurement of Frequency Shift Characteristics Based on LiNbO_3 Waveguide Electro-Optic Intensity Modulator

High-speed and wide-band LiNbO3 waveguide electro-optic intensity modulator has drawn great attention in the field of optical fiber communication and sensor. This paper reports the research results on the measurement of frequency shift characteristics of Mach-Zehnder electro-optic intensity modulator. Two measurement methods of frequency shift characteristics for high and low frequency modulations are studied in theory and experiment and demonstrate different results. The realization of a multi-wavelength optical source based on Mach-Zehnder electro-optic intensity modulator has been introduced. The technique to reach the maximum intensity for interesting shift frequency, particularly for heterodyne detection of Brillouin distributed optical fiber sensing, has been given.

Magneto and Electro-Optic Intensity Modulator Based on Liquid Crystal and Magnetic Fluid Filled Photonic Crystal Fiber

We propose a novel light intensity modulator based on magnetic fluid and liquid crystal（LC） filled photonic crystal fibers（PCFs）. The influences of electric and magnetic fields on the transmission intensity are theoretically and experimentally analyzed and investigated. Both the electric and magnetic fields can manipulate the molecular arrangement of LC to array a certain angle without changing the refractive index of the LC. Therefore, light loss in the PCF varies with the electric and magnetic fields whereas the peak wavelengths remain constant. The experimental results show that the transmission intensity decreases with the increase of the electric and magnetic fields. The cut-off electric field is 0.899 V/um at 20 Hz and the cut-off magnetic field is 195 m T. This simple and compacted optical modulator will have a great prospect in sensing applications.

Modulation Depth Based on Frequency-shift Characteristic of LiNbO3 Waveguide Electro-optic Intensity Modulator

The modulation depth, defined according to practical modulation results, which changes with the microwave power and its frequency, is significant for systems utilizing the frequency-shift characteristic of the LiNbO3 waveguide Electro-Optic Intensity Modulator （EOIM）. By analyzing the impedance mismatch between the microwave source and the EOIM, the effective voltage applied to the RF port of the EOIM is deprived from the microwave power and its frequency. Associating with analyses of the phase velocity mismatch between the microwave and the optical wave, the theoretical modulation depth has been obtained, which is verified by experimental results. We provide a method to choose the appropriate modulation depth to optimize the desired sideband through proper transmission bias for the system based on the frequency-shift characteristic of the EOIM.

Novel frequency shift keying modulation based on fiber Bragg gratings and intensity modulators

This paper proposed and investigated a novel frequency shift keying （FSK） modulation based on two fiber Bragg gratings （FBGs） and two intensity modulators. Then the transmission of 10 Gbit/s FSK signal after a 50 km single mode fiber （SMF） was studied in this paper. The power penalty at the bit error rate （BER） of 10-9 was below 0.1 dB. The FSK modulation system can be applied to optical transmission system

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

Intensity modulation characters of orthogonally polarized HeNe lasers with different optical feedback level

This paper demonstrates the intensity modulation characters of orthogonally polarized HeNe lasers with different optical feedback level generated by the variable reflectivity of external reflector. The modulation depths of the orthogonally polarized frequencies are increased when the optical feedback level becomes strong. It also observes that the modulation amplitudes are different for different external cavity length. Based on the vectorial extension of Lamb＇s semi-classical theory, it finds that the calculations are consistent with the experimental results.

Prostate specific antigen bounce after intensity-modulated radiation therapy in an Asian population

Objective:Serum prostate specific antigen(PSA)is commonly used to evaluate treatment response after definitive radiation therapy(RT).However,PSA levels can temporarily rise without a clear reason,termed“PSA bounce”,and often engender great anxiety for both patients and physicians.The present study aimed to determine the prevalence and factors that predict“PSA bounce”after intensity-modulated radiation therapy(IMRT),and the relevance to biochemical failure and cancer recurrence in an Asian population.Methods:We retrospectively reviewed 206 patients who received IMRT for prostate cancer from 2004 to 2012 in the National Cancer Centre Singapore.These patients were followed up with regular PSA monitoring.We defined“PSA bounce”as a rise of 0.1 ng/mL,followed by two consecutive falls.Patients with biochemical failure(PSA nadir t 2 ng/mL)were further evaluated for cancer recurrence.Results:Sixty-one patients(29.6%)experienced“PSA bounce”,at a median time of 16 months and lasted for 12 months.Age remained the most consistent predictor of the incidence,duration and extent of“PSA bounce”.Other contributory factors included baseline PSA,Gleason score and PSA nadir.Hormonal therapy and prostate volume did not affect this phenomenon.Sixteen patients(7.8%)developed biochemical recurrence,at median time of 32 months,of which 11 were confirmed to have metastatic disease.The median follow-up time was 71 months.

Clinical study on concurrent and sequential therapy of intensity modulated radiation therapy (IMRT) combined with NP regimen chemotherapy in the treatment of middle and advanced non-small cell lung cancer

Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin (NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; (4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall re- sponse, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.

The impact of intensity modulated radiotherapy on the skin dose for deep seated tumors

Objective: The purpose of this study was to investigate the impact of intensity modulated radiotherapy (IMRT) on surface doses for brain, abdomen and pelvis deep located tumors treated with 6 MV photon and to evaluate the skin dose calculation accuracy of the XIO 4.04 treatment planning system. Methods: More investigations for the influences of IMRT on skin doses would increase its applications for many treatment sites. Measuring skin doses in real treatment situations would reduce the uncertainty of skin dose prediction. In this work a pediatric human phantom was covered by a layer of 1 mm bolus at three treatment sites and thermoluminescent dosimeter (TLD) chips were inserted into the bolus at each treatment site before CT scan. Two different treatment plans [three-dimensional conformal radiation therapy (3DCRT) and IMRT] for each treatment sites were performed on XIO 4.04 treatment planning system using superposition algorism. Results: The results showed that the surface doses for 3DCRT were higher than the surface doses in IMRT by 1.6%, 2.5% and 3.2% for brain, abdomen and pelvis sites respectively. There was good agreement between measured and calculated surface doses, where the calculated surface dose was 15.5% for brain tumor calculated with 3DCRT whereas the measured surface dose was 12.1%. For abdomen site the calculated surface dose for IMRT treatment plan was 16.5% whereas the measured surface dose was 12.6%. Conclusion: The skin dose in IMRT for deep seated tumors is lower than that in 3DCRT which is another advantage for the IMRT. The TLD readings showed that the difference between the calculated and measured point dose is negligible. The superposition calculation algorism of the XIO 4.04 treatment planning system modeled the superficial dose well.

Design of a Reflective Intensity Optical Fibre Bundle Displacement Sensor

Optical fibre sensor has the advantages of small size,light weight,anti⁃electromagnetic interference,and high measurement accuracy,which has important applications in research and industrial production.To design an optical fibre displacement sensor(OFBDS)with simple structure and high measurement accuracy,the unified model of the commonly used OFBDS structures was proposed and the feasibility of the intensity⁃modulation of multi⁃structural optical fibre bundles was analysed based on the arrangement characteristics of the fibre bundle end⁃face.The intensity⁃modulation characteristic of different fibre bundles was analysed,and the single coil coaxial fibre bundle was chosen as the fibre probe in this study.The sensor hardware system was designed.Lastly,the calibration experiment,temperature interference experiment,changes of measured plane surface area,and the dynamic experiment were conducted.Results showed that the sensor linear measurement range was about 3 mm,and the sensor system had excellent static and dynamic characteristics.

Dosimetric study comparing intensity modulated and conformal pelvic radiotherapy boost plans in locally advanced cancer cervix in NCI-Cairo

Objective:This study was to compare 5 field conformal technique to the intensity modulated radiotherapy (IMRT) 8 fields technique in boosting locally advanced cancer cervix cases after external beam radiotherapy with respect to target volume coverage and dose to normal tissues. Methods:We conducted a single institutional comparative dosimetric analysis of 10 patients with cancer cervix who was presented to radiotherapy department in National Cancer Institute, Cairo in period between June 2012 to September 2012 and received a CRT boost in the place of planned brachytherapy after large field pelvic radiotherapy (PRT) with concurrent chemotherapy were retrospectively identified. All tumors were situated in the low central pelvis. Two plans were done for every patient; one using the 8 fields IMRT and the second one using 5 fields' 3DCRT the two techniques were then compared using dose volume histogram (DVH) analysis for the PTV, bladder, rectum and both femoral heads. Results:Comparing different DVHs, it was found that the planning target volume (PTV) was adequately covered in both plans while it was demonstrates that the 8 fields IMRT technique carried less doses reaching OARs (rectum, bladder, both femoral heads). Conclusion:From the present study, it is concluded that IMRT technique spared more efficiently OARs than CRT technique but both techniques covered the PTV adequately so whenever possible IMRT technique should be used.

Intensity Modulated Proton Therapy for Re-Irradiation of Bulky Loco-Regional Recurrent Breast Cancer: A Case Report

Patients with recurrent breast cancer to chest wall, who had previous irradiation, are difficult to manage and have limited options. Several reports described the use of photon therapy, hyperthermia, and brachytherapy. This is a case report of a 72-year-old female with Stage IIIA (pT3N1M0) invasive ductal carcinoma of the right breast status post modified radical mastectomy. The patient developed recurrence to the chest wall and one internal mammary lymph node one year later. She received 3-D conformal photon radiation therapy for this recurrence. Two years later, she had progression of the recurrence at the right chest wall and axillary and internal mammary lymph nodes. She was treated with intensity modulated proton therapy (IMPT) for a total of 6600 cGy in 33 fractions. However, four months later, she was found to have biopsy-proven isolated metastatic disease at her right bicep, which was again treated with IMPT for a dose of 6000 cGy in 20 fractions. Proton beam therapy was used in this case to spare dose to the brachial plexus, heart and lung while optimally irradiating the recurrent tumors. At last follow up, the patient is alive and has been disease free for 39 months. This report describes the technique and dosimetry for this unique case, which also reviewed recent series of re-irradiation using proton beam.

Subcarrier Intensity Modulated Optical Wireless Communications:A Survey from Communication Theory Perspective

Subcarrier intensity modulation with direet detection is a modulatiou/detection technique tbr optical wireless communication systems, where a pre-modulated and properly biased radio frequency signal is modulated on the intensity of the optical carrier. The most important benefits of subcarrier intensity modulation are as follows： 1） it does not provide irreducible error floor like the conventional on-off keying intensity modulation with a fixed detection threshold; 2） it provides improved spectral efficiency and supports higher order modulation schemes; and 3） it has much less implementation complexity compared to coherent optical wireless communications with heterodyne or homodyne detection. In this paper, we present an up-to-date review of subcarrier intensity modulated optical wireless communication systems. We survey the error rate and outage performance of subcarrier intensity modulations in the atmospheric turbulence channels considering different modulation and coding schemes. We also explore different contemporary atmospheric turbulence fading mitigation solutions that can be employed for subcarrier intensity modulation. These solutions include diversity combining, adaptive transmission, relay assisted transmission, multiple-subcarrier intensity modulations, and optical orthogonal frequency division multiplexing. Moreover, we review the performance of subcarrier intensity modulations due to the pointing error and synchronization error.

Comparative Study between Patients Treated with Conventional Radiotherapy and IMRT with Chemotherapy for Stage III - IVA Nasopharyngeal Carcinoma: A Single Institution Retrospective Report

Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ2 = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.

Dual-Wavelength Linearization of Radio-over-Fiber Link for Broadband Access and Ubiquitous Sensing

Radio-over-Fiber （RoF） technologies have been considered to be a promising solution to broadband access and ubiquitous sensing. We present a novel approach using dual-wavelength lights to suppress the nonlinear intermodulation distortion in intensity-modulated RoF link both theoretically and experimentally. The system we proposed rminly consists of two Laser Diodes （LDs） at different wavelengths, a commercial available Mach-Zehnder Modulator （MZM） and a Photo Detector （PD）. More than 25 dB suppression of the Third-order Interrnodulation Distortion （IMD3） is achieved by adjusting the wavelength and opti- cal power of the laser. Besides, the output of the MZM is then sent to the photodetector via a single fiber, which simplifies the system complexity for distrbution of RF signals over long distances.

Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer:A treatment planning comparison

AIM： To compare the volumetric-modulated arc ther- apy （VMAT） plans with conventional sliding window intensity-modulated radiotherapy （c-IMRT） plans in esophageal cancer （EC）. METHODS： Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning sys- tem： three using c-IMRT with 5 fields （5F）, 7 fields （7F） and 9 fields （gF）, and two using VMAT with a single arc （1A） and double arcs （2A）. The treatment plans were designed to deliver a dose of 60 Gy to the plan-ning target volume （PTV） with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normal- ized to 95% of the PTV that received 100% of the pre- scribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk （OAR） such as lungs, spinal cord and heart. Monitor units （MU） and normal tissue complication probability （NTCP） of OAR were also reported. RESULTS： Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different Io- cations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions： in cervical and upper thoracic EC, the conformity index （CI） was higher in VMAT （1A 0.78 and 2A 0.8） than in c-IMRT （5F 0.62, 7F 0.66 and 9F 0.73） and homogeneity was slightly better in c-IMRT （7F 1.09 and 9F 1.07） than in VMAT （1A 1,1 and 2A 1.09）, Lung V30 was lower in VMAT （1A 12.52 and 2A 12.29） than in c-IMRT （7F 14.35 and 9F 14.81）. The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT （1A 0.76 and 2A 0.74） was higher than in c-IMRT （5F 0.63 Gy and 7F 0.67 Gy）, and homogeneity was almost similar between VMAT and c-IMRT. V20 （2A 21.49 Gy vs 7F 24.59 Gy and 9F 24.16 Gy） and V30 （2A 9.73 Gy vs 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy） of lungs in VMAT were lower than in c-IMRT, but low doses to lungs （V5 and Vl0） were increased. V30 （1A 48.12 Gy vs 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy）, V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc. CONCLUSION： Compared with c-IMRT, VMAT, especial- ly the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.

Role of radiation therapy in gastric adenocarcinoma

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

Helical tomotherapy and volumetric modulated arc therapy:New therapeutic arms in the breast cancer radiotherapy

AIM To analyse clinical and dosimetric results of helical tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in complex adjuvant breast and nodes irradiation.METHODS Seventy-three patients were included(31 HT and 42 VMAT). Dose were 63.8 Gy(HT) and 63.2 Gy(VMAT) in the tumour bed, 52.2 Gy in the breast, 50.4 Gy in supraclavicular nodes(SCN) and internal mammary chain(IMC) with HT and 52.2 Gy and 49.3 Gy in IMC and SCN with VMAT in 29 fractions. Margins to particle tracking velocimetry were greater in the VMAT cohort(7 mm vs 5 mm).RESULTS For the HT cohort, the coverage of clinical target volumes was as follows: Tumour bed: 99.4% ± 2.4%; breast: 98.4% ± 4.3%; SCN: 99.5% ± 1.2%; IMC:96.5% ± 13.9%. For the VMAT cohort, the coverage was as follows: Tumour bed: 99.7% ± 0.5%, breast: 99.3% ± 0.7%; SCN: 99.6% ± 1.4%; IMC: 99.3% ± 3%. For ipsilateral lung, Dmean and V20 were 13.6 ± 1.2 Gy, 21.1% ± 5%(HT) and 13.6 ± 1.4 Gy, 20.1% ± 3.2%(VMAT). Dmean and V30 of the heart were 7.4 ± 1.4 Gy, 1% ± 1%(HT) and 10.3 ± 4.2 Gy, 2.5% ± 3.9%(VMAT). For controlateral breast Dmean was 3.6 ± 0.2 Gy(HT) and 4.6 ± 0.9 Gy(VMAT). Acute skin toxicity grade 3 was 5% in the two cohorts.CONCLUSION HT and VMAT in complex adjuvant breast irradiation allow a good coverage of target volumes with an acceptable acute tolerance. A longer follow-up is needed to assess the impact of low doses to healthy tissues.

The role of radiotherapy in localised and locally advanced prostate cancer

For a patient suffering from non-metastatic prostate cancer,the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board,to be explained carefully to the patient to obtain his informed consent.External beam radiotherapy is now delivered by intensity modulated radiotherapy,considered as the gold standard.From a radiotherapy perspective,low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy,or brachytherapy if patients meet the required eligibility criteria.Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4e6 months of androgen deprivation therapy;intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health.High-risk prostate cancer,i.e.high-risk localized and locally advanced prostate cancer,requires intensity modulated radiotherapy with long-term(≥2 years)androgen deprivation therapy with luteinizing hormone releasing hormone agonists.Post-operative irradiation,either immediate or early deferred,is proposed to patients classified as pT3pN0,based on surgical margins,prostate-specific antigen values and quality of life.Whatever the techniques and their degree of sophistication,quality assurance plays a major role in the management of radiotherapy,requiring the involvement of physicians,physicists,dosimetrists,radiation technologists and computer scientists.The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation.A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.