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Job satisfaction and employee performance need special attention from the organization because the better it is expected to impact organizational performance positively. Thus, this study examines the effect of workload variables, coworker and supervisor support on job satisfaction and work performance at PT. REA Kaltim Plantations. This study uses a quantitative approach through a survey questionnaire on 150 permanent staff of PT. REA. The data were collected through the census method and analyzed using Structural Equation Modeling-Partial Least Square assisted by Warp-PLS. The result indicates that employee performance is affected by workload. Besides that, the workload has a significant effect on job satisfaction. Also, this study found that supervisor supports positively and significantly affects job satisfaction. Next, coworker support positively and significantly affects work performance. In addition, coworker support positively and significantly affects job satisfaction. Next, job satisfaction has a positive and significant effect on job performance. In conclusion, this study has successfully examined the factors influencing job satisfaction and performance. Also, this study concludes that workload affects employee work performance. Giving employees more work in a way that does not overwhelm them can improve their performance. Employees are given workloads that improve performance according to their abilities, do not provide excessive tasks, ensure comfort, demand completion of tasks as needed, and have the necessary skills.

The purpose of this study is to test and find out how much influence training, career path, and compensation have on employee performance at PT Gosen Pacific Suksesmakmur. The sample determination in this research is an employee of PT Gosyen Pacific Suksesmakmur itself who is still actively working by using the Sampling technique saturated with a total of 50 respondents, the method in data collection is carried out using questionnaires and data processing using SPSS 25. The analysis used uses statistical models which include Frequency Test, Descriptive Test, Validity Test, Reability Test, Determination Test (R2), T Test, and F Test. The results obtained partially stated that the training variable (X1) had a significant effect with a calculated tcount> ttabel , the variable X2 career path had a significant effect with a calculated tcount> ttabel , the variable X3 compensation had no significant effect with a calculated tcount< ttabel . The results obtained simultaneously fcount> ftabel 104,824 > 2.57 training, career path, and compensation have a significant effect on employee performance, so it can be concluded that independent variables affect dependent variables.

Purpose of Review Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges. Recent Findings In the current era, multidisciplinary management with access to a combination of functional imaging and targeted molecular profiling can provide important disease characterisation, guide individualised management and improve patient outcome. Multiple treatment options are now available, and combination and novel therapies are being explored in clinical trials. Summary Precision medicine is highly relevant for a heterogenous disease like NEN. The integration of dual-tracer functional PET/CT imaging, molecular histopathology and genomic data has the potential to be used to gain a more comprehensive understanding of an individual patient’s disease biology for precision diagnosis, prognostication and optimal treatment allocation.

Purpose The existing literature involving director compensation has been concentrating on its absolute or intrinsic values. Although the relevant studies have generated mixed findings, research in other fields suggests that the power of an incentive may be determined by its value relative to the chosen referencing standard more than its absolute value. This study aims to investigate how relative director pay affects corporate investment efficiency. Design/methodology/approach This study takes a fresh theoretical viewpoint by framing the investigation using the dimensional comparison theory and proposing that a directorship also presents a relative value that may influence the board’s performance. Ordinary least squared regressions and two-stage system generalised method of moments are used to analyse 14,267 firm-year observations. Findings The empirical results suggest that the relative director pay is a better estimate of the power of the incentive than the absolute pay. A positive association between the relative director pay and investment efficiency is evident, while the absolute pay has no significant effect on investment decisions. Director overcompensation, however, will cancel out the positive effect of director compensation on investment efficiency. Firms with relatively lower unexpected investment (UI) level benefit the most from an increase in the relative director pay, while neither absolute nor relative director pay affects investment choices in firms with a high UI level because of significantly more overcompensation. Originality/value To the best of the authors’ knowledge, this study is the first attempt to investigate the effect of relative director pay. It is also the first to examine the role of dimensional comparison in strategic decisions which is the single untended comparison framework in the director pay design. The current director pay structure has emphasised social and temporal equality by standardising the pay structure and vesting the equity-based pay over a long period. Yet it ignores the fact that people decide their commitment level by comparing the reward with an internal referent too. The findings speak to the dimensional comparison theory in that the inequality emanated from dimensional or internal comparison may be accentuated by the perceived equality in other comparison frameworks, driving the different performances in the roles one assumes.

Purpose:BRAF V600E mutant metastatic colorectal cancer represents a significant clinical problem, with combination approaches being developed clinically with oral BRAF inhibitors combined with EGFR-targeting antibodies. While compelling preclinical data have highlighted the effectiveness of combination therapy with vemurafenib and small-molecule EGFR inhibitors, gefitinib or erlotinib, in colorectal cancer, this therapeutic strategy has not been investigated in clinical studies.Patients and Methods:We conducted a phase Ib/II dose-escalation/expansion trial investigating the safety/efficacy of the BRAF inhibitor vemurafenib and EGFR inhibitor erlotinib.Results:Thirty-two patients with BRAF V600E positive metastatic colorectal cancer (mCRC) and 7 patients with other cancers were enrolled. No dose-limiting toxicities were observed in escalation, with vemurafenib 960 mg twice daily with erlotinib 150 mg daily selected as the recommended phase II dose. Among 31 evaluable patients with mCRC and 7 with other cancers, overall response rates were 32% [10/31, 16% (5/31) confirmed] and 43% (3/7), respectively, with clinical benefit rates of 65% and 100%. Early ctDNA dynamics were predictive of treatment efficacy, and serial ctDNA monitoring revealed distinct patterns of convergent genomic evolution associated with acquired treatment resistance, with frequent emergence of MAPK pathway alterations, including polyclonal KRAS, NRAS, and MAP2K1 mutations, and MET amplification.Conclusions:The Erlotinib and Vemurafenib In Combination Trial study demonstrated a safe and novel combination of two oral inhibitors targeting BRAF and EGFR. The dynamic assessment of serial ctDNA was a useful measure of underlying genomic changes in response to this combination and in understanding potential mechanisms of resistance.

The rapid growth of active investors in Indonesia stock market raises awareness on the importance of investors’ skill needed in analyzing and choosing profitable stock. One of the method knows to analyze profitable stock in the market is Magic Formula introduce by Joel Grenblatt -part of value investing. Magic Formula is a method on choosing a profitable stock in a simple way based on combination of both High Earnings Yield and High Return on Capital. The period use in this research is from 2016 – 2020. This research use LQ 45 stock listed in Indonesia Stock Exchange. This qualitative research used secondary data which is analyzed using backtesting simulation. The result of this research shows that Magic Formula’s Stock Portfolio build based on data consist of different number of stock: 15, 20, and 25 stock; combination of both high Earnings Yield and High Return on Capital. The Magic Formula’s Portfolio formed based on the LQ 45 stock has higher aritmathic average return compare to LQ 45 return and even the 15-stock-based portfolio beat the Indonesia Composite Index average return. However on the CAGR rate of return, the calculation show that the return of the Magic Formula Portfolio below the return of Indonesia Composite Index

Stratification of patients with colorectal peritoneal metastases (CRPM) using RAS/BRAF mutational status may refine patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to analyse the association of RAS/BRAF status and their variants, with clinicopathological variables and survival outcomes in patients who have undergone CRS ± HIPEC.A single centre, peritonectomy database was interrogated for patients with CRPM who underwent peritonectomy procedures between 2010 and 2020.During the study period, 174 patients were included. Molecular status was obtained on 169 patients, with 68 (40.5%) KRAS, 25 (14.8%) BRAF and 6 (3.6%) NRAS mutations detected. Patients with BRAF mutations were more likely to be mismatch repair deficient (dMMR) (BRAF 20%, KRAS 4.4%, wild type 8.6%, p = 0.015). Most common BRAF and KRAS variants were, V600E (80%) and G12D (39.7%), respectively. BRAF V600E was independently associated with worse overall (median: 28 months, multivariate: HR 2.29, p = 0.026) and disease-free survival (median: 8 months, multivariate: HR 1.8, p = 0.047). KRAS G12V was a strong prognostic factor associated with disease-free survival (median: 9 months, HR 2.63, p = 0.016). dMMR patients (14/161, 8.7%) exhibited worse median overall survival compared to those with proficient MMR (dMMR 27 months, pMMR 29 months p = 0.025).This study highlights the importance of molecular analysis in CRPM stratification. BRAF V600E mutations predict poor outcomes post CRS and HIPEC and may help refine patient selection for this procedure. Molecular analysis should be performed preoperatively to characterise prognosis and guide perioperative therapeutic options.

Pharmacogenomics guided dosing for fluoropyrimidine and irinotecan chemotherapies for patients with cancer (PACIFIC-PGx): study protocol of a multicentre clinical trial

Cacat lahir merupakan kelainan kondisi fisik atau genetik bawaan menyebabkan komplikasi Kesehatan dan keterlambatan perkembangan yang signifikan seperti dalam fungsi intelektual dan perilaku yang adaptif. Tujuan dari penelitian ini adalah untuk melihat jenis kecacatan, kategori kecacatan dan penyebab kecacatan pada anak laki-laki dan perempuan. Cross-sectional merupakan metode yang digunakan pada penelitian ini. Teknik pengambilan sampling yang digunakan pada penelitian ini adalah convenience sampling dengan membagikan questioner kepada orang tua yang bersedia menjadi responden pada sekolah luar biasa yang berada di Sumatra Selatan. Hasil pada penelitian ini melibat jumlah responden total 96 responden dengan 53 orang laki-laki dan 43 orang perempuan. Tidak ada perbedaan yang signifikan terhadap jenis cacat (0.49) yang diderita oleh anak laki-laki dan perempuan, tidak ditemukannya korelasi antara tingkat keparahan kecacatan (0.91) terhadap jenis kelamin serta tidak adanya perbedaan yang signifikan terhadap penyebab kecataan (0.35) antara anak laki-laki dan perempuan. Kecacatan intelektual (62.5%) dan kecacatan ringan (54.2%) merupakan kecacatan yang paling banyak ditemukan. Penyebab kecacatan yang utama adalah kekurangan asam folat dan mulitivitamins pada saat kehamilan yaitu 49%.

Methane (CH4) is a potent greenhouse gas but its sources remain poorly quantified in the Eastern Mediterranean and Middle East (EMME) region where major oil and gas production takes place. Light alkanes, such as ethane (C2H6), are co-emitted with CH4 by oil and gas activities and are promising tracers for quantifying the methane emissions from this sector. Cyprus is an ideal location for studying the composition of regional air masses and for characterizing different emission source signatures at a regional scale. A Picarro G2401 greenhouse gas analyzer and two field-based Gas Chromatography Flame Ionization Detectors (GC-FID) for Non-Methane Hydrocarbons (NMHC) measurements were deployed during two campaigns, one in “urban” (Nicosia) and one in “regional background” (Cape Greko) environment respectively. The campaign at the regional background site consisted in continuous methane and NMHCs (C2-C12) observations using a mobile laboratory that was deployed at the south-eastern edge of the island between December 2021 and February 2022. This location was chosen to capture airmasses of remote south and eastern origin, uninfluenced by local sources. We use these observations to 1) evaluate the significance of long-range transported versus local sources in Cyprus, 2) identify and document regional anthropogenic methane sources, and 3) assess the accuracy of the EDGAR sectoral emission inventory over EMME. Positive Matrix Factorization (PMF) analysis of the NMHC dataset resulted in the identification of four distinct sources namely tropospheric background, urban, heavy oil combustion, and transported from Middle East. The latest occurred during three distinct episodes and on average, had the highest NMHC concentrations. Generally, the different urban and regional signatures/sources displayed good and variable correlations between CH4 and C2 to C6-NMHCs. By investigating the PMF results together with CH4 concentrations and an atmospheric dispersion model (FLEXPART), we provide a comprehensive characterization of the pollution sources at regional scale over the Eastern Mediterranean region.

Background The gold standard treatment for locally advanced rectal cancer is total mesorectal excision after preoperative chemoradiotherapy. Response to chemoradiotherapy varies, with some patients completely responding to the treatment and some failing to respond at all. Identifying biomarkers of response to chemoradiotherapy could allow patients to avoid unnecessary treatment-associated morbidity rate. While previous studies have attempted to identify such biomarkers, none have reached clinical utility, which may be due to heterogeneity of the cancer. In this study, potential human gene and microbial biomarkers were explored in a cohort of rectal cancer patients who underwent chemoradiotherapy. Methods RNA sequencing was carried out on matched tumour and adjacent normal rectum biopsies from patients with rectal cancer with varying chemoradiotherapy responses treated between 2016 and 2019 at two institutions. Enriched genes and microbes from tumours of complete responders were compared with those from tumours of others with lesser response. Results In 39 patients analysed, enriched gene sets in complete responders indicate involvement of immune responses, including immunoglobulin production, B cell activation and response to bacteria (adjusted P values Conclusion These results identify potential genetic and microbial biomarkers of response to chemoradiotherapy in rectal cancer, as well as suggesting a potential mechanism of complete response to chemoradiotherapy that may benefit further testing in the laboratory.

Supplementary material

Fluoropyrimidines (FP; 5-fluorouracil, capecitabine, and tegafur) are a commonly prescribed class of antimetabolite chemotherapies, used for various solid organ malignancies in over 2 million patients globally per annum. Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the critical enzyme implicated in FP metabolism. DPYD variant genotypes can result in decreased DPD production, leading to the development of severe toxicities resulting in hospitalization, intensive care admission, and even death. Management of toxicity incurs financial burden on both patients and healthcare systems alike. Upfront DPYD genotyping to identify variant carriers allows an opportunity to identify patients who are at high risk to suffer from serious toxicities and allow prospective dose adjustment of FP treatment. This approach has been shown to reduce patient morbidity, as well as improve the cost-effectiveness of managing FP treatment. Upfront DPYD genotyping has been recently endorsed by several countries in Europe and the United Kingdom. This review summarizes current knowledge about DPD deficiency and upfront DPYD genotyping, including clinical and cost-effectiveness outcomes, with the intent of supporting implementation of an upfront DPYD genotyping service with individualized dose-personalization.

Patients with neuroendocrine tumours (NET) are at nutritional risk due to symptoms and treatment side-effects. Current evidence-based guidelines lack information regarding optimal nutritional management. This study aimed to describe health professional knowledge and management of nutrition complications in GEP NET patients and summarise current international practice.Multidisciplinary health professionals who regularly provide care for NET patients, were invited to participate in a 21-item online survey. Survey questions asked about symptom prevalence, nutrition screening, assessment practices, and vitamin deficiency screening and supplementation practices. General demographic information was recorded.In total 73 health professionals completed the survey. Many worked in Australia (52%) and the United Kingdom (19%). Most responses were provided by medical oncologists (25%), nurses (23%) and dietitians (30%). Diarrhoea and fatigue were reported as the most common symptoms (86% and 60%, respectively) and of greatest concern to patients with NET (80% and 52%, respectively). Provision of advice for symptom management, weight loss and food intolerances was reported by 92%, 59% and 41%, respectively. Overall, 38% carried out screening/assessment for malnutrition and screening for vitamin deficiencies, respectively. Health professionals reported on the lack of NET-specific nutrition guidelines and hence used general oncology nutrition guidelines to direct their practice.This is the first international survey of nutrition knowledge and practices among NET health professionals. Results highlight variations in nutrition screening and assessment practices and identify a gap in NET-specific guidelines addressing nutrition issues in this at-risk patient group.

Keep in mind, energy is fluctuating. The dependence of electricity production from fossil fuels is a valuable lesson for stakeholders to think about and inspire the creation of the latest technology. Although the contribution of fossil fuels has grown the flow of industry in various worlds, they must limit it as early as possible. We set this research up based on a quantitative approach that aims to examine the impact of fossil fuels electricity generation on GDP per unit of energy used, electricity production capacity, and access to electricity. Indonesia and Malaysia as countries that represent empirical objectivity to be reviewed on how the causality of the research objectives for the period 2013-2020. We collected the data source through The Global Economy, which is very concerned with highlighting global economic developments. Multiple regression and path analysis support this work. Interestingly, the three findings for the case study in Indonesia support the design hypothesis (p 0.05). Besides the economic element, it does not balance the results due to demographic factors in Indonesia, which are larger in composition than Malaysia. Future agenda need to discuss the implications of further referring to this research.

The prevalence of elderly patients with resectable colorectal peritoneal metastases (CRPM) is increasing. This study aimed to compare short and long-term outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPM in patients above and below 70 years of age.This was a retrospective, 10-year analysis of 90-day major morbidity and mortality, and long-term survival.Thirty-two (21.3%) of 150 consecutive patients who underwent CRS and HIPEC during the study period were aged 70 and older. PCI (P = 0.04), perioperative chemotherapy use (P 0.01) and organ resections (rectum P = 0.04, diaphragm P = 0.03) were less in the over 70 group. There was no significant differences in major morbidity (P = 0.19) and mortality (P = 0.32). There was also no difference in 5-year overall survival (OS) (≥70: 26% vs.70: 39%; P = 0.68) and disease-free survival (DFS) (≥70: 25% vs.70: 14%; P = 0.22). Age above 70 was not independently associated with worse OS (HR 1.55, P = 0.20) and DFS (HR 1.07, P = 0.81).The surgical management of CRPM appears safe and feasible in this elderly population. Appropriate selection of elderly patients for such radical intervention is reinforced by the comparable survival with those under 70.

Tri Dharma perguruan tinggi adalah kewajiban bagi setiap dosen yang harus dijalankan setiap semester dalam tahun ajaran. Adapun Tri Dharma Perguruan Tinggi meliputi pengajaran, penelitian, dan pengabdian kepada masyarakat. Pengabdian kepada masyarakat memberikan esensi penting secara sosial agar memberikan manfaat secara langsung bagi masyarakat umum. Selain itu juga memberikan pengalaman bagi dosen yang bersangkutan agar dapat melakukan inovasi pengetahuan. Pengabdian kepada masyarakat ini dilaksanakan di RM Kuliner dan Pemancingan Sangabut Kayu Agung. Pengabdian ini dilaksanakan oleh dosen lingkungan Universitas MDP dengan persetujuan dari Rektor Universitas MDP. Usaha yang akan hadir yaitu para Usaha Kuliner untuk mengikuti Workshop Pemanfaatan Digital marketing dan Pembuatan Laporan Keuangan Bagi Usaha Usaha Kuliner. Dalam pelatihan ini nanti diharapkan para usaha dapat melakukan pembuatan Digital marketing dan Pembuatan Laporan Keuangan guna membantu dalam kegiatan operasional usaha mereka dan selain itu juga dapat lebih meningkatkan kompetensi para Usaha Kuliner RM Pondok Kolam Sangabut di Kota Kayu Agung.

Background Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial. Methods A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC. Results Twelve studies met the inclusion criteria (n = 2,463 patients). Ten were retrospective cohort, one was prospective cohort, and one was a prospective randomised by design. Patients who received NAC followed by CRS and HIPEC experienced no difference in major perioperative morbidity and mortality compared with patients who underwent surgery first (SF). There was no difference in overall survival at 3 years, but at 5 years NAC patients had superior survival (relative risk [RR] 1.31; 95% confidence interval [CI] 1.11–1.54, P < 0.001). There were no differences in 1- and 3-year, disease-free survival (DFS) between groups. Study heterogeneity was generally high across all outcome measures. Conclusions Patients who received neoadjuvant chemotherapy did not experience any increase in perioperative morbidity or mortality. The potential improvement in 5-year overall survival in patients receiving NAC is based on limited confidence due to several limitations in the data, but not sufficiently enough to curtail its use. The practice of NAC in this setting will remain heterogeneous and guided by retrospective evidence until prospective, randomised data are reported.

BACKGROUND: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type). METHODS: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life). RESULTS: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27–0.39], p

Bonsai ornamental plants are dwarf plants which are generally planted in shallow pots. The main element in bonsai is harmony between pots and plants, in addition to harmony between pots and plants there are also other elements such as trunk size, tree height, root distribution, twigs, and leaf size as well as diseases and pests that attack the bonsai plants need to be considered. The difficulty of the community in conducting consultations and the unavailability of funds and time, so that the community has never conducted consultations about diseases and pests that attack their bonsai plants to experts or plant extension workers from the relevant agencies. Therefore, it is necessary to take action to anticipate the increasing number of bonsai farmers who do not consult on diseases and pests of bonsai plants. This is due to the delay in the diagnosis of the disease. The unavailability of experts or plant extension workers who are close, the community does not have time to conduct consultations and requires money. An expert system is a computer-based system that uses knowledge, facts, and techniques and reasoning in solving problems that can usually only be solved by an expert in the field. The Certainty Factor method is efficient enough to be used in diagnosing the diseases and pests of the bonsai plant. This system can provide early diagnosis of diseases and pests on the bonsai plant based on the symptoms and intensity of the symptoms that are visible from the outside. Users only need to enter the Web to take the first step in solving bonsai plant diseases and pests and choose the symptoms of the disease they are experiencing without having to ask an expert directly. This system is made web-based with PHP programming language and MySQL database.

Setiap tahunnya, terdapat banyak mahasiswa baru dari luar kota datang untuk melanjutkan jenjang pendidikannya di tempat baru. Secara tidak langsung kebutuhan akan tempat tinggal akan meningkat secara proposional, terutama di daerah yang dekat dengan institusi pendidikan tinggi. Tapi sering kali keterbatasan informasi membuat para calon mahasiswa maupun mahasiswa baru mengalami kebingungan dalam mencari informasi tempat tinggal atau kost. Oleh karena itu, penulis berniat mengembangkan sebuah aplikasi web kost-kostan yang dimana dapat menyediakan informasi tersebut dan menghubungkan penyedia kost dengan pencari kost. Aplikasi web juga sangat fleksibel sehingga dapat diakses kapan saja dan dari mana saja asal terhubung dengan internet. Selama proses penelitan ini penulis menerapkan metode Extreme Programming (XP). Penelitian nantinya akan menghasilkan sebuah aplikasi web dimana penyedia kost dapat mempromosikan kost-kostannya dan juga pencari kost dapat mencari kost yang diinginkan dengan segala informasi sudah tertera didalam aplikasi. Dari penelitian ini penulis menyimpulkan aplikasi web kost-kostan sangat dibutuhkan pada saat ini. Penerapan XP sebagai metode penelitian juga sangat cocok dikarenakan jangka waktu yang cukup singkat dan tentunya metode XP sangat terstruktur selama penerapannya.

Objective Healthcare experiences, quality of life and psychosocial needs of patients with Neuroendocrine tumours (NETs) will be assessed to identify differences between NET sub-groups and inform the design of supportive care services. Methods This study constitutes phase one of a three-phase mixed-methods multi-site study with NET patients (n = 123). Demographic, clinical and patient reported outcome questionnaire data was collected. Results No differences in patient reported outcomes were found beyond symptoms of diarrhoea and flushing between NET sub-groups. For combined NET patients, the majority reported negative experiences in their understanding of the explanation of what was wrong with them (67%); receiving written information about their cancer (69%), their family/carer receiving all the information required to care for them (61%); and the usefulness of information about NETs online (66%). NET patients reported at least one moderate-to-high need for disease specific information (63%). Medium- to large-sized differences in quality of life subscales were also observed with the functioning group reporting more anxiety compared to population norms. Conclusions There is a need to improve the current provision of information for people with NETs. Practice implications These findings will inform the design and development of an informational resource to facilitate improved understanding for patients with NETs.

Extended peritonoid drug sensitivity data

Patient characteristics & analyses.

Best response according to histological grade

Purpose:Combination immunotherapy with anti–CTLA-4 and anti–PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs.Patients and Methods:CA209-538 is a prospective multicenter clinical trial in patients with advanced rare cancers. Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every three weeks for four doses, followed by nivolumab 3 mg/kg every two weeks and continued for up to 96 weeks, until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1. The primary endpoint was clinical benefit rate (CBR; complete remission + partial remission + stable disease).Results:Twenty-nine patients with advanced NETs received treatment. Three (10%) patients had low-, 13 (45%) had intermediate-, and 13 (45%) had high-grade tumors; lung was the most common primary site (39%). The objective response rate was 24% with a CBR of 72%; 43% of patients with pancreatic neuroendocrine neoplasms (NEN), and 33% of patients with atypical bronchial carcinoid achieved an objective response. The median progression-free survival was 4.8 months [95% confidence interval (CI): 2.7–10.5] and overall survival was 14.8 months (95% CI: 4.1–21.3). Immune-related toxicity was reported in 66% of patients with 34% experiencing grade 3/4 events.Conclusions:Combination immunotherapy with ipilimumab and nivolumab demonstrated significant clinical activity in subgroups of patients with advanced NETs including patients with atypical bronchial carcinoid and high-grade pancreatic NENs.

Peritonoid sensitivity to standard care chemotherapeutic regimens ex vivo.

Extended data peritonoid genomic analyses

Histological diagnoses

Purpose:Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown.Experimental Design:CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing.Results:Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications.Conclusions:Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

Summary of drug panels and peritonoid genomic information

Supplementary Methods

Extended data peritonoid drug testing platform, patient specific responses

Characterisation of CRPM tissue and peritonoids.

Validation of CRISPR-edited ATP1A1 HCT116 cell lines for use as control lines.; Genotypic validation of CRISPR-edited HCT116 cells lines; AMPK activation sensitises HCT116 AMPKα1 wild type but not AMPKα1-KO edited colorectal cancer cells to metformin.

Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Accounting and Data Analytics, La Trobe Business School, College of Arts, Social Sciences and Commerce, La Trobe University, Victoria, Australia.

Script for data analyses

Supplemental material, sj-docx-1-opp-10.1177_10781552231167554 for Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists by Sarah Glewis, Senthil Lingaratnam, Mei Krishnasamy, Jennifer H Martin, Jeanne Tie, Marliese Alexander and Michael Michael in Journal of Oncology Pharmacy Practice

Introduction Peritoneal metastases confer the worst survival amongst all sites of metastatic colorectal cancer. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for patients with isolated colorectal peritoneal metastases (CRPM). The aim of this study was to evaluate the outcomes following CRS and HIPEC for CRPM from published high volume cohort studies and to highlight the latest controversies and future directions of CRPM treatment. Materials and methods A systematic review was performed on published studies on the treatment outcomes of CRS and HIPEC for colorectal peritoneal metastases. Results Twenty studies met the inclusion criteria for the systematic review. The median survival for all patients ranged from 14.6 to 60.1 months. The 5-year overall survival ranged from 23.4% to 52%. For patients with complete cytoreduction, the median survival was 25 to 49 months. Major morbidity and mortality ranged from 15.1% to 47.2% and 0% to 4.5%, respectively. Conclusion CRS and HIPEC for the treatment of CRPM is safe and current evidence suggests it improves both median and disease-free survival. However, the efficacy of intraperitoneal chemotherapy, in particular oxaliplatin, has recently come under scrutiny. Accordingly, higher quality evidence is urgently required to contribute to multidisciplinary and international consensus on CRPM treatment strategies.

Fiduciary is a process of transferring ownership rights to an object based on trust with the provision that the object whose ownership rights are transferred remains in the power of the object owner. As for fiduciary guarantees, which are guarantees for the rights of tangible or intangible movable objects, immovable objects such as buildings. In this case, the building cannot be subject to mortgages as stated in Law Number 04 of 11996 concerning mortgages which are stated to remain in the power of the fiduciary giver as collateral for the settlement of certain debts, where the priority position is the fiduciary recipientx against other creditors. On this occasion, the author will discuss a discussion entitled, “Juridical Review of the Execution of Guarantees x Fiduciary x Debtors x Defaults”. In this discussion, the research methodx that is usedx to fulfill related material is the normative legal research methodx which uses data collection techniques from written sources such as books and heritage studies as well as other supporting sources. Looking at the title, it is conveyed regarding the execution of fiduciary guarantees, where this can be done if the debtor or fiduciary giver deviates from the promise, in this case the execution is carried out by implementing executorial title as stated in Article v15vayat2. As for what is stated regarding the sale of xobjects that are objects of fiduciary guarantees for the power of fiduciary recipients through general customers. Sales proceeds are obtained by obtaining the highest price so that it will benefit both parties based on applicable law. The purpose of writing this journal is to know the procedure for executing fiduciary collateral objects, to find out whether creditors can transfer the ownership rights of collateral objects to third parties, to find out whether debtors can transfer property rights to collateral objects during the guarantee period, to know the role of the police in securing the execution of fiduciary collateral objects

CO2 mineralization via aqueous Mg/Ca/Na-carbonate (MgCO3/CaCO3/Na2CO3) formation represents a huge opportunity for the utilization of captured CO2. However, large-scale mineralization is hindered by slow kinetics due to the highly hydrated character of the cations in aqueous solutions (Mg2+ in particular). Reaction conditions can be optimized to accelerate carbonation kinetics, for example by the inclusion of selected additives that promote competitive dehydration of Mg and subsequent agglomeration, nucleation and crystallization. Towards tracking mineralisation and these steps of the reaction, neutron scattering presents unprecedented advantages over traditional techniques for time-resolved in situ measurements. However, a setup providing continuous solution circulation to ensure reactant system homogeneity for industrially relevant CO2-mineralizsation was currently available for use on neutron beamlines. We therefore undertook the design, construction, testing and implementation of such a self-contained reactor rig for use on selected neutron beamlines at the ISIS Neutron and Muon Source (Chilton, UK). The design ensured robust attachment via suspension from the covering flange to stabilize the reactor assembly and all fittings, as well as facilitating precise alignment of the entire reactor and sample (test) cell with respect to beam dimension and direction. The assembly successfully accomplished the principal tasks of providing a continuous flow of the reaction mixture for homogeneity, quantitative control of CO2 flux into the mixture as well as temperature and pressure regulation throughout the reaction and measurements. The design is discussed, with emphasis placed on the reactor including its geometry, components and all technical specifications. Descriptions of the offbeamline bench tests, safety and functionality, as well as the installation on beamlines and trial experimental procedure are provided, together with representative raw neutron scattering results.

Body surface area (BSA)–based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants. Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%. The identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.

INTRODUCTION: It is well recognized that pathological complete response (pCR) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) confers a positive survival advantage. Despite this, a small proportion of patients can develop distant recurrence, and these are the patients that will likely benefit from adjuvant therapy. This study aims to investigate the role of PET/CT as a functional imaging to stratify patients according to their risk of distant recurrence. METHODS: This is a retrospective analysis of a prospectively maintained database in a single quaternary teaching hospital from 2010 to 2019. All consecutive cases of locally advanced rectal cancer with restaging PET/CT were included. The primary outcome measure was 5-year OS and distant recurrence-free survival. RESULTS: A pCR and complete metabolic response (CMR) were identified in 47 (18%) patients and 73 (27.4%) patients respectively. Of these, 26 patients had both pCR and CMR and these patients remained free of local and distant recurrence at their last censored date. Patients with both pCR and CMR achieved the highest 5-year overall survival of 96.2%, followed by those with pCR and incomplete CMR (iCMR) of 85.7%, non-pCR and CMR of 85.1% and non-pCR and iCMR of 83.1%. Independent predictors for 5-year distant recurrence-free survival were pathological and PET metabolic response, nodal staging and lymphovascular invasion (LVI). CONCLUSION: In conclusion, a PET/CT has the potential to better stratify patients of their risk of distant metastasis. However, a larger validation cohort is required before these findings can be translated to clinical utility.

Background Locally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates. Methods A systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded. Results Of the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%. Conclusion A validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.

Research Purposes. This study aims to determine the impact of the level of sustainability and reputation of KAP that can affect the assessment results of the credit rating process carried out by PEFINDO. Research Methods. In this study, the ordinal logistic regression analysis model is used to determine the probability of obtaining a credit rating for a company. Financial variable is described through level of sustainability prediction as calculated by using the value of the Altman Z-Score, while non-financial variable is described through the reputation of the KAP. There were 25 samples of companies that obtained credit ratings in a row from 2014 to 2018 by PEFINDO tested in this study. Research Result and Findings. The results of this study state that the level of sustainability prediction has a positive effect; whilst KAP reputation, which are not affiliated with Big 4, has a negative effect on the results of companies' credit ratings