tbuckley/cabot-search huggingface dataset:
Statewide survey on the management of psychosocial distress by oncologists
Authors: W. F. Pirl, A. Muriel, L. Schapia, V. Hwang, C. Moore, J. Temel, A. Kornblith, J. C. Holland
Journal: Journal of Clinical Oncology (2006)

8601 Background: Although the NCCN has published guidelines for the management of psychosocial distress, no data exists on how oncologists manage it in clinical practice. This study surveyed oncologists in Massachusetts on their estimated rates of distress in their patients, beliefs about distress, and practice patterns. Methods: All Massachusetts oncologists belonging to ASCO were e-mailed an electronic survey up to three times. Survey completion was anonymous and a small incentive was offered for participation. Descriptive statistics and cross-tabulations were compiled. Chi-squared analyses investigated differences in rates. Results: 393 e-mail addresses were identified. 338 surveys were delivered, but the e-mail survey could be blocked by SPAM filters. Ninety-nine responses were obtained yielding a response rate of 29%. Oncologists estimated that 77% (sd=23%) of their patients experience distress, but only 33% (sd=20%) have distress that warrants treatment. Emotional problems unrelated to illness, practical problems, and coping with illness were the three most frequently encountered forms of distress. Sixty-five percent of oncologists reported that they routinely screened for psychosocial distress, but only 3% use a screening instrument. Almost all reported that they would at least consider using a brief screening instrument (93%). Lack of time was identified as the main barrier to screening, but lack of knowledge about treatment of distress was the only variable that predicted lower rates of screening (p=.03). While reported rates of referrals to mental health professionals were high, the majority (85%) reported that they directly address the psychosocial distress in their practice and almost half reported that they initiate psychotropic medications (45%). Conclusions: The majority of oncologists report that they do some screening and management of psychosocial distress in their clinical practices. Although screening appears to mainly be done through the usual clinical encounter, research has shown that this method has a poor rate of detection for psychological disorders. Despite the fact that the NCCN recommends the use of screening instruments and most oncologists report interest in using them, oncologists rarely actually use such measures. No significant financial relationships to disclose.
Heme Excess Impairs the Maturation of Proerythroblasts From Patients with Diamond Blackfan Anemia (DBA) and 5q- Myelodysplastic Syndrome (MDS)
Authors: Zhantao Yang, Sioban B Keel, Akiko Shimamura, Aaron T. Gerds, Bart L. Scott, Janis L. Abkowitz
Journal: Blood (2012)
High Frequency and Cell Dose of Invariant NKT Cells In the Graft Are Associated with Lack of Clinically Significant Acute Gvhd In T Cell-Replete Sibling Allografts
Authors: Aristeidis Chaidos, Richard M. Szydlo, Edward J. Kanfer, Francesco Dazzi, Donald H. MacDonald, David Marin, Dragana Milojkovic, Jiri Pavlu, John Davis, Katayoun Rezvani, Amin Rahemtulla, Irene Roberts, Jane F. Apperley, Anastasios Karadimitris
Journal: Blood (2010)
Per Capita Caps in Medicaid — Lessons from the Past
Authors: Andrew J. Goodman-Bacon, Sayeh S. Nikpay
Journal: New England Journal of Medicine (2017)

Interview with Andrew Goodman-Bacon on a proposal for setting limits on federal Medicaid spending and how it may affect access to care. (09:07)Download Analysis of U.S. experience with a pre-Medicaid financing system suggests that Speaker of the House Paul Ryan's proposal for per capita caps in Medicaid would result in restrictions on coverage and benefits rather than state innovations to reduce program costs.
Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials
Authors: Stanley B Cohen, Yoshiya Tanaka, Xavier Mariette, Jeffrey R Curtis, Eun Bong Lee, Peter Nash, Kevin L Winthrop, Christina Charles-Schoeman, Krishan Thirunavukkarasu, Ryan DeMasi, Jamie Geier, Kenneth Kwok, Lisy Wang, Richard Riese, Jürgen Wollenhaupt
Journal: Annals of the Rheumatic Diseases (2017)

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA.Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest.6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure.This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results.
Efficacy and safety of bendamustine plus bortezomib in relapsed/refractory multiple myeloma: A phase I/II trial.
Authors: J. R. Berenson, O. Yellin, A. Bessudo, R. Boccia, S. Noga, D. Gravenor, D. Patel-Donnelly, R. S. Siegel, T. Kewalramani, E. J. Gorak, R. Swift, D. Bensen-Kennedy
Journal: Journal of Clinical Oncology (2011)

8070 Background: Novel, effective treatment combinations are needed for pts with relapsed/refractory multiple myeloma (MM). Bendamustine is a unique akylating agent active in MM. Bortezomib is approved for treatment of MM and is effective in combination with alkylators (eg, melphalan and cyclophosphamide). This open-label, phase I/II study assessed the efficacy/safety of bendamustine plus bortezomib in relapsed/refractory MM. Methods: Pts ≥18 years, with measurable, relapsed/refractory MM received escalating doses of bendamustine IV at 50, 70, or 90 mg/m2 (days 1 and 4) plus bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11) for up to 8 28-day cycles. Dose-limiting toxicity (DLT) was assessed after cycle 1. A standard 3+3 approach was used to determine the maximum tolerated dose (MTD). The MTD cohort was expanded to 40 pts. Endpoints included response, duration of response (DOR), time to progression (TTP), and safety. Results: 38 pts (median age 67; range 43-89) received study drug and were included in the analysis. Pts received a median 3.5 (range 1-21) prior therapies, including bortezomib in 71% and alkylators in 68%. A median of 3 treatment cycles (range 1-9) were administered, with study treatment ongoing in 14 pts (median cycles to date: 4 [range 1-7]). No DLT was observed; bendamustine 90 mg/m2 plus bortezomib 1.0 mg/m2 was designated the MTD. Grade 3/4 adverse events in ≥10% of pts were neutropenia (13 pts [34%]), thrombocytopenia (7 [21%]), and anemia (4 [11%]). Grade 3/4 infection occurred in 3 pts (8%); grade 3 renal failure in 2 pts (5%). No grade 3/4 peripheral neuropathy (PN) was observed; grade 1/2 PN was reported in 10 pts (26%), but 8 of these had baseline PN. In 36 evaluable pts, the objective response rate (ORR) was 47%, including 1 very good partial response, 6 partial responses, and 10 minimal responses; ORR was 52% in the 90 mg/m2cohort (n = 27), and 37% and 40% in pts with prior bortezomib or alkylators, respectively. An additional 17 pts had stable disease for a clinical benefit rate of 94%. Median DOR and TTP have not been reached. Conclusions: Bendamustine 90 mg/m2 plus bortezomib 1.0 mg/m2 was well tolerated with promising efficacy in this heavily pretreated population. Updated phase II results will be presented.
The myth of pure perception
Authors: Gerald L. Clore, Dennis R. Proffitt
Journal: Behavioral and Brain Sciences (2016)

Firestone & Scholl (F&S) assume that pure perception is unaffected by cognition. This assumption is untenable for definitional, anatomical, and empirical reasons. They discount research showing nonoptical influences on visual perception, pointing out possible methodological "pitfalls." Results generated in multiple labs are immune to these "pitfalls," suggesting that perceptions of physical layout do indeed reflect bioenergetic resources.
Long-term complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): the spectrum of chronic problems in patients who survive an episode of SJS/TEN necessitates multidisciplinary follow-up
Authors: H.Y. Lee, S.A. Walsh, D. Creamer
Journal: British Journal of Dermatology (2017)

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse reactions to drugs that cause a life‐threatening eruption of mucocutaneous blistering and epithelial sloughing. While the acute complications of SJS/TEN are well described, it is increasingly recognized that survivors may develop delayed sequelae, some of which can be associated with significant morbidity. Studies of long‐term SJS/TEN outcomes mostly focus on mucocutaneous and ocular complications. However, other internal organs, such as the respiratory tract and gastrointestinal tract, can be affected. Psychological sequelae are also frequent following the trauma of widespread epidermal necrolysis. An appreciation of the 'chronic' phase of SJS/TEN is needed by clinicians caring for individuals who have survived the acute illness. This review aims to provide an update on the breadth and range of sequelae that can affect patients in the months and years following an acute episode of SJS/TEN.
Impact of G-CSF on Outcomes of Pregnancy in Women with Severe Chronic Neutropenia
Authors: Laurence A. Boxer, Audrey Anna Bolyard, Tracy M. Marrero, Lan Phan, Jordan M. Bond, Blanche P Alter, Mary Ann Bonilla, Daniel Link, Peter E. Newburger, Philip S. Rosenberg, Akiko Shimamura, David C. Dale
Journal: Blood (2011)
Distinct Properties of Leukemia Stem Cells in Primary Refractory Acute Myeloid Leukemia
Authors: Jason H. Mendler, Marlene Balys, Umayal Sivagnanalingam, Allison Eberhardt, Korinne Thorne, Tzu-Chieh Ho, Mark W. LaMere, Samuel Moore, Helene McMurray, Jason R. Myers, John M. Ashton, Kristen O'Dwyer, Jane L. Liesveld, Laura M. Calvi, Michael W. Becker
Journal: Blood (2015)
ATPS-80ANTI-TUMORIGENESIS OF LENTI-VIRUS sh-HDGF IN RAT C6 GLIOMA MODEL
Authors: Shu-Shong Hsu, Chih-Hao Chen, Li-Feng Liu
Journal: Neuro-Oncology (2015)

BACKGROUND: In our previous studies, we found Hepatoma derived growth factor (HDGF) is a mitogenic growth factor in the progression of human glioma. METHODS: In this paper, we study the gliomagenesis role of HDGF in syngenic glioma rat model by Lenti-virus sh-HDGF (LV-shHDGF) infection and tumors growth inhibition was analysis by MRI scanning and western blot analysis. This work was supported by NSC101-2314-B-075B-003-MY2 and VGHKS102-022. RESULTS: We found all glioma tumors growth after implanting but only HDGF knock down tumors had a significant reduction in the tumor size at the 4th-week MRI-scanning. After tumor volume was quantified on serial brain section, we found a 10-folds of reduction in the tumor size was observed in HDGF knock down tumors than scrambles (p < 0.005). By survival analysis, rats with gliomas had a less median survival of 25 days and the HDGF knock down group was still alive from the time point of implanting. According to the pathological analysis, the HDGF knock down tumors presented a significant cell apoptosis and reduction in the Ki67 mitotic index, CD31 angiogenesis index, and ANG-4 that exhibited markedly reduced tumor growth and blood vessel formation than controls. In addition, Western blot analysis showed exogenous HDGF increased the expression of PI3K, phospho-Akt, phospho-FAK, phospho-MDM2, PCNA and transcription factors of Ik-B, NF-kB, cFos, ANG-4, and HIF-a in a dose-dependent manner; however, these tumorigenesis moleculars were significantly decreased in HDGF knock cells. CONCLUSIONS: We concluded that HDGF is a mitogenic growth factor in the progression of glioma and it can be a useful therapeutic target for clinical management of glioma in the future.
A Novel Protocol Decreased Incidence of Hepatic Veno-Occlusive Disease and Improved Results in Hematopoietic Cell Transplantation for Patients with b-Thalassemia Major
Authors: Chunfu Li, Fuyu Pei, Qi Li, Jianyun Liao, Shengli An, Xuedong Wu, Yuelin He, Xiaoqin Feng, Xiaohui Zhou, Lei Shi, Huaying Liu, Na Li, Wenfeng Xu, Wanxia Tan, Zhiyong Peng, Jiaqi Chen, Yuqiong Ren
Journal: Blood (2014)
External validation of a tumor derived 5-gene prognostic signature (OncoDefender-CRC) for recurrence (R) of stages I/II colorectal cancer (CRC).
Authors: P. F. Lenehan, L. A. Boardman, D. W. Fry, E. R. Heyman, J. Ohrnberger, W. P. Worzel
Journal: Journal of Clinical Oncology (2011)

3559 Background: About 10-15% of stage I and 25-30% of stage II CRC patients (pts) will recur after potentially curative surgery. Correctly identifying these ‘high risk’ pts is a significant unmet medical need. We hypothesized that a tumor genomic test would better predict the chances of tumor R within 36 months (mo) than current NCCN Guidelines (NCCN). Methods: Archival formalin-fixed paraffin-embedded primary adenocarcinoma tissues (median storage 7 yrs; range 4-15) obtained at initial curative resection (R0) were retrieved for 109 stage I/II (pT1-4 pN0 M0) colon cancer and 6 stage I (pT1-2, pN0 M0) rectal cancer pts (median age 65; range 36-90) from 2 US and 2 European sites. These sites were different from the tissue sources previously used to generate the test through genetic programming analysis of 422 CRC- and stroma-related genes. Pts had tumor R by 36 mo (n=46) or confirmed non-recurrence (NR) for ≥36 mo (n=69) after surgery; none had received neoadjuvant or adjuvant therapy. Tumor gene expression was assessed by RT-PCR with custom 384-well TaqMan® Low Density Arrays (Applied Biosystems) using RNA that had satisfied rigorous quality control parameters. Results: For stages I/II CRC (n=115), the dichotomous rule correctly classified 32/46 R and 38/69 NR pts: sensitivity (S) 0.70, specificity (SP) 0.55. ‘High risk’ pts had a significantly higher probability of R by 36 mo (51%) than ‘low risk’ pts (27%): hazard ratio (HR) 2.06 (95% CI: 1.10, 3.86; p=0.020; Cox regression). This was independent of age, T-stage, grade, tumor location and lymphovascular invasion. NCCN (V.2.2011) could not differentiate 36-mo R vs NR in this population: S 0.72, SP 0.42; HR 1.38 (95% CI: 0.73, 2.63; p=0.315). Notably, Stage I CRC pts (n=29; 13R, 16NR) deemed ‘high risk’ recurred by 36 mo at a rate (82%) more than triple that for ‘low risk’ pts (22%): S 0.69, SP 0.88; HR 4.89 (95% CI: 1.48, 16.13; p=0.009). Conclusions: OncoDefender-CRC is able to differentiate early stage CRC pts at high risk vs low risk for R within 36 mo after surgery better than NCCN. This novel stage I/II CRC prognostic test should prove useful for optimizing post-op clinical management and for pt stratification in therapeutic clinical trials.
Interactions of noradrenaline and cortisol and the induction of indelible memories
Authors: René Hurlemann, Wolfgang Maier, Dirk Scheele
Journal: Behavioral and Brain Sciences (2016)

The glutamate amplifies noradrenergic effects (GANE) model emphasizes the role of focal glutamate-noradrenaline interactions in creating functional hotspots for prioritized processing of salient stimuli. Here, we briefly outline current evidence that synergistic action of noradrenaline and cortisol enables emotional stimuli to gain privileged access to amygdala-hippocampus circuits, eventually resulting in the formation of indelible memories and posttraumatic stress disorder (PTSD).
Dickkopf 1 (Dkk1) Regulates Hematopoietic Stem Cell Regeneration
Authors: Heather A Himburg, Phuong L Doan, Xiao Yan, Mamle Quarmyne, Liman Zhao, Evelyn Tran, Nelson J. Chao, Jeffrey Harris, John P Chute
Journal: Blood (2015)
Seeing same GP is linked to fewer hospital admissions
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Patients who see the same GP are less likely to be admitted to hospital for certain conditions, researchers at the Health Foundation have found.1

The researchers analysed primary and secondary care records of over 230 000 patients in England aged 62 to 82 from 2011 to 2013.

Their analysis, published in The BMJ , showed that patients who saw the same GP a greater proportion of the time experienced fewer admissions to hospital for conditions that could be managed in primary care than other patients. Emergency admissions for these conditions accounted for £1.42bn …
Early 18fluorodeoxyglucose PET Scan as a Prognostic Tool in Diffuse Large B-Cell Lymphoma Patients Treated with An Anthracycline-Based Chemotherapy Plus Rituximab.
Authors: Violaine Safar, Jehan Dupuis, Fabrice Jardin, Christophe Fruchart, Stéphane Bardet, Pierre Vera, Herve Tilly, Michel Meignan, Emmanuel Itti, Corinne Haioun
Journal: Blood (2009)
Ublituximab, an Optimized Anti-CD20 Monoclonal Antibody, Demonstrates Greater NK-Mediated ADCC Than Rituximab in Waldenstrom's Macroglobulinemia Patients Supporting a Therapeutic Strategy with Ublituximab
Authors: Magali Le Garff-Tavernier, Linda Herbi, Christophe de Romeuf, Jean-Francois Prost, Patrice Debré, Rémi Urbain, Véronique Leblond, Vincent Vieillard, Hélène Merle-Béral
Journal: Blood (2012)
Splicing Inhibition By Spliceostatin_A Is a Promising Therapeutic Strategy in Chronic Lymphocytic Leukaemia
Authors: Marta Larrayoz, Stuart Blakemore, Rachel Dobson, Matthew Rose-Zerilli, Renata Walewska, Matthew Blunt, Minoru Yoshida, David G Oscier, Mark Cragg, Andrew J Steele, Jonathan C Strefford
Journal: Blood (2014)
JAK2 mutations and CRLF2 rearrangements in Down Syndrome-Associated Acute Lymphoblastic Leukemia in Japan
Authors: Isamu Hanada, Kiminori Terui, Tsutomu Toki, Ko Kudo, Tomohiko Sato, Takuya Kamio, Shinya Sasaki, Yoshihiro Takahashi, Yasuhide Hayashi, Kanji Sugita, Seiji Kojima, Kenichi Koike, Yoshiyuki Kosaka, Masao Kobayashi, Etsuro Ito
Journal: Blood (2011)
Factors Predictive of Relapse of Hematologic Malignancies in Pediatric Patients Post Allogeneic Hematopoietic Cell Transplantation
Authors: Nirali N Shah, Michael J. Borowitz, Seth M. Steinberg, Mary Lefell, Nancy Robey, Christopher Gamper, Heather J. Symons, David Loeb, Alan S Wayne, Allen R. Chen
Journal: Blood (2012)
Results of the Western Swiss Fertility Preservation Network for young women with breast cancer: Réseau Romand de Cancer et Fertilité (RRCF).
Authors: K. Zaman, M. Bellavia, A. Ambrosetti, M. Primi, A. Ifticene Treboux, M. Kohlik, P. Brioschi, G. de Candolle, D. de Ziegler, P. Petignat, J. Delaloye, D. Wunder, L. Perey
Journal: Journal of Clinical Oncology (2011)

e19599 Background: Infertility secondary to adjuvant chemotherapy is a major problem in young women with breast cancer. We developed a multidisciplinary-multicenter network, the “RRCF”, aiming to offer a medically assisted procreation program (MAP) without delaying the systemic treatment. We analyzed if this goal was achievable. Methods: Patients (pts) were referred from the French-speaking part of Switzerland. After multidisciplinary assessment and discussion with the pts we proceeded with urgent MAP, when indicated. Oktay’s protocol (Oktay et al, J Clin Endocrinol Metab. 2006;91:3885-3890.) was used for oocytes collection and ovarian biopsies (OB) were considered for selected cases. Data were collected prospectively: characteristics of the patients and tumors, chronology of events, material collections, estradiol and baseline anti-Müllerian hormone (AMH) levels. Results: Among 44 pts referred between Oct 2006 and Feb 2010, 26 opted for urgent MAP (median age 32.5; range: 25-40) and 18 declined (median age 36; range: 28-42). Three pts had OB and 23 pts had controlled ovarian hyperstimulation (COH). First MAP visit occurred before (85%) or after (15%) surgery. COH succeeded in 22 pts with the collection of 2-52 oocytes/pt (median 10.5). Median baseline AMH level was 15.7 pmol/L (range <1-450). Median antral follicle count was 13 (range 3 to 21). The means of estradiol levels at day 5 and at ovulation were 0.39 nmol/L (<0.09-1.57) and 1.73 nmol/L (0.36-3.97), respectively. The median time from final surgery for breast cancer to the start of adjuvant chemotherapy was 31 days (range 18-56). Conclusions: Urgent fertility preserving measures organized by a dedicated multidisciplinary network is feasible without unduly delaying the start of adjuvant chemotherapy. The letrozole-based ovarian stimulation protocol is effective at collecting oocytes while maintaining plasma estradiol levels close to the physiological limits.
Sensitivity and Cross-Resistance to Deoxynucleoside Analogs in Childhood Acute Leukemia.
Authors: Gertjan J. Kaspers, Isabelle Hubeek, Christian M. Zwaan, Monique L. Den Boer, Gritta E. Janka-Schaub, Elisabeth R. Van Wering, Brenda E. Gibson, Ursula Creutzig, Godefridus J. Peters
Journal: Blood (2004)
A Randomized Controlled Trial of Ethyl Glucuronide-Based Contingency Management for Outpatients With Co-Occurring Alcohol Use Disorders and Serious Mental Illness
Authors: Michael G. McDonell, Emily Leickly, Sterling McPherson, Jordan Skalisky, Debra Srebnik, Frank Angelo, Roger Vilardaga, Jenny R. Nepom, John M. Roll, Richard K. Ries
Journal: American Journal of Psychiatry (2017)

Objective: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior. Method: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study participation. Contingency management included the variable magnitude of reinforcement "prize draw" procedure contingent on EtG-negative samples (<150 ng/mL) three times a week and weekly gift cards for outpatient treatment attendance. Urine EtG, drug test, and self-report outcomes were assessed during the 12-week intervention and 3-month follow-up periods. Results: Contingency management participants were 3.1 times (95% CI=2.2–4.5) more likely to submit an EtG-negative urine test during the 12-week intervention period, attaining nearly 1.5 weeks of additional alcohol abstinence compared with controls. Contingency management participants had significantly lower mean EtG levels, reported less drinking and fewer heavy drinking episodes, and were more likely to submit stimulant-negative urine and smoking-negative breath samples, compared with controls. Differences in self-reported alcohol use were maintained at the 3-month follow-up. Conclusions: This is the first randomized trial utilizing an accurate and validated biomarker (EtG) to demonstrate the efficacy of contingency management for alcohol dependence in outpatients with serious mental illness.