Prevalence of exercise-induced oxygen desaturation after recovery from SARS-CoV-2 pneumonia and use of lung ultrasound to predict need for pulmonary rehabilitation.

BACKGROUND: Persistence of breathlessness after recovery from SARS-CoV-2 pneumonia is frequent. Recovery from acute respiratory failure (ARF) is usually determined by normalized arterial blood gases (ABGs), but the prevalence of persistent exercise-induced desaturation (EID) and dyspnea is still unknown. METHODS: We investigated the prevalence of EID in 70 patients with normal arterial oxygen at rest after recovery from ARF due to COVID-19 pneumonia. Patients underwent a 6-min walking test (6MWT) before discharge from hospital. We recorded dyspnea score and heart rate during 6MWT. We also investigated the possible role of lung ultrasound (LU) in predicting EID. Patients underwent a LU scan and scores for each explored area were summed to give a total LU score. RESULTS: In 30 patients (43%), oxygen desaturation was >4% during 6MWT. These patients had significantly higher dyspnea and heart rate compared to non-desaturators. LU score >8.5 was significantly able to discriminate patients with EID. CONCLUSION: In SARS-CoV-2 pneumonia, ABGs at discharge cannot predict the persistence of EID, which is frequent. LU may be useful to identify patients at risk who could benefit from a rehabilitation program.

Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

BACKGROUND: Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. METHODS: Seventy-nine women (age range between 24 and 69 years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. RESULTS: The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). CONCLUSIONS: Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

Realization of a high power optical trapping setup free from thermal lensing effects.

Transmission of high power laser beams through partially absorbing materials modifies the light propagation via a thermally-induced effect known as thermal lensing. This may cause changes in the beam waist position and degrade the beam quality. Here we characterize the effect of thermal lensing associated with the different elements typically employed in an optical trapping setup for cold atoms experiments. We find that the only relevant thermal lens is represented by the TeO2 crystal of the acousto-optic modulator exploited to adjust the laser power on the atomic sample. We then devise a simple and totally passive scheme that enables to realize an inexpensive optical trapping apparatus essentially free from thermal lensing effects.

Effectiveness of manual therapy in COPD: A systematic review of randomised controlled trials.

PURPOSE: Manual therapy (MT) has been proposed in pulmonary rehabilitation programmes for patients with chronic obstructive pulmonary disease (COPD), but an updated systematic review of the evidence is lacking. We aimed to systematically review the effectiveness of MT interventions, alone or added to exercise, on lung function, exercise capacity and quality of life in COPD patients, compared to other therapies (e.g. exercise alone) or no treatment. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Physiotherapy Evidence Database, and Cochrane Central Register of Controlled Trials databases, using the terms: COPD, manual therapy, manipulation, joint mobilisation, osteopathic manipulation. Only randomised controlled trials (RCT) were considered. RESULTS: Out of 555 articles screened, 6 fulfilled the inclusion criteria. The study designs were heterogeneous (with different intervention schedules) and there was a high risk of bias. No effect on lung function was found, while results on exercise capacity were contrasting. MT had no effect on quality of life, although valid measures were available only in one study. Only mild adverse events were reported. CONCLUSIONS: Few RCTs of poor methodological quality are available on the effects of MT in COPD. More and better quality RCTs are needed before this technique can be included in rehabilitation programmes for these patients.

Questionnaire of Cognitive Schema Activation in Sexual Context: translation and psychometric properties of the Italian version.

The Questionnaire of Cognitive Schema Activation in Sexual Context (QCSASC) is a validated and widespread used measure to assess the self-schemas elicited during sexual negative events in both men and women. The current study aimed to test the psychometric characteristics of the Italian version of the QCSASC in both heterosexual men and women. After linguistic translation, the psychometric properties (internal consistency, construct and discriminant validity) were evaluated in 1038 participants (435 men and 603 women, 767 healthy and 271 clinicals complaining of sexual problems). Confirmatory factor analyses showed a not satisfactory fit of the original factor structure of the QCSASC versions. Principal component analyses were performed highlighting two new factorial structures, further validated with CFAs ("Helpless" and "Unlovable"). Cronbach's alpha, composite reliability and average variance extracted were used as internal consistency measures. Moreover, the QCSASC showed a strong association with emotional response and sexual functioning, being able to differentiate between sexually clinical and control group. Current findings support the validity and the internal consistency of the QCSASC Italian version and allows to assess dysfunctional cognitive schemas activated when facing sexual problematic situations for both clinical and research purposes.

Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics. AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics. METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection. RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed. CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg).

The aim of this study was to explore the efficacy and toxicities of a combined regimen of bevacizumab plus immunotherapy and chemotherapy (BIC) and the circulating T regulatory cells (Treg) in metastatic renal cell cancer (mRCC). Nephrectomized mRCC patients were enrolled into a multicenter single-arm dose-finding study with five escalated dose levels of chemotherapy with intravenous gemcitabine and 5-fluorouracil associated with fixed intravenous doses of bevacizumab, subcutaneous low doses of interleukin-2, and interferon-α-2a. An expanded cohort (phase II study) was treated at the recommended dose for additional safety and efficacy information according to minimax Simon two-stage design. Blood samples for Treg were collected and evaluated by fluorescence-activated cell sorting (FACS) analysis on cycle 1. Fifty-one patients were entered to receive one of five dose levels. Median age was 58 years (male 67 %, pretreated 49 %): 15 patients were low risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, while 27 and nine were respectively intermediate- and high-risk patients. More frequent grade 3 and 4 toxicities included nonfebrile neutropenia, thrombocytopenia, and fever. Among patients evaluable for response (49), 29.5 % had partial response and 37 % stable disease. Overall median time to progression and median overall survival were 8.8 and 22.67 months, respectively. We observed a rapid increase in the percentage of Treg after immunotherapy and a reduction after bevacizumab only in patient who obtained a partial response or stable disease. The BIC was feasible, well tolerated, and shown interesting activity. Further studies are needed to explore if Treg could have a role in clinical response in mRCC treated with bevacizumab.

Unconsummated marriage: can it still be considered a consequence of vaginismus?

Unconsummated marriage (UM) is the failure to perform successful sexual intercourse at the beginning of the marriage. Vaginismus has been traditionally reported as the leading cause. ED is also a leading cause for UM. This appears to be a significant problem in the conservative middle-Eastern societies and in the developing countries, where couples are strongly prevented by religious rules and cultural taboos from sexual experiences before wedding. One could think that according to major sexual freedom and information, in Western countries UM is now disappearing, but the number of observed cases by the authors in 2008-2012 was relevant. The aim of this study is to compare the literature data from non-Western countries with the features of UM in Western ones, focusing on cases observed by the authors, and to verify whether the etiology of UM proposed in the '70s is still relevant, outlining any changes that occur in current reality. In our series, traditional appearance of UM is no more effective, while the role of man is undervalued, because of his frailty, lack of self-confidence and ignorance, expressing a social and cultural change of man's role in the couple.

Perceptions and opinions of men and women on a man's sexual confidence and its relationship to ED: results of the European Sexual Confidence Survey.

The European Sexual Confidence Survey examined the opinions of men and women on the link between a man's sexual confidence and functional (erectile and orgasmic) and emotional (satisfaction and self-confidence) aspects of sex and life in general. The online survey of sexually active adults (25-64 years of age) was conducted in 12 European countries using multiple-choice questions and predefined statements on sexual confidence. Erectile function was assessed by erection hardness score (EHS). Of 8576 respondents (4246 men, 4330 women), 23.9% reported non-optimal erectile hardness (EHS3) for themselves or their partners. 79.0% believed that an ability to sexually satisfy their partner is most closely linked to a man's sexual confidence. One in three linked a man's sexual confidence to erection hardness and ability to reach orgasm. The majority (∼94.0%) believed that it is important for a man to be sexually confident for good sex and that being able to have good sex enables men to have greater satisfaction with life overall. Lack of sexual confidence due to insufficient erection rigidity was considered by most respondents (∼65.0%) to reduce a man's confidence about the next sexual encounter and also his self-confidence and self-esteem overall.

What do men and women ask a helpline on sexual concerns? Results of an Italian telephone counselling service.

INTRODUCTION: In Europe, helplines have become a common counselling service for men and women who are seeking advice for sexual problems. Despite this, relatively few peer-reviewed reports on this subject have been published in the last decade. AIM: To investigate the range of sexual concerns reported by users of an Italian helpline and to describe the differences, if any, between male and female callers; to identify the overlap among sexual difficulties and the associations between the variables of the study. METHODS: The study included selected records of the calls received during the 3-year period between 2006 and 2008 (n = 944). Data were analysed using descriptive statistics and bivariate analysis. RESULTS: Users were more often male (62.2%), aged between 26 and 35 years, who had not sought any previous help. The most frequently reported male sexual difficulties were erectile dysfunction (ED) and premature ejaculation, while the majority of female callers reported vaginismus and orgasmic disorder (OD). We found an association between desire disorder (DD) and ED in men (41.7%), and between OD and DD in women (36.8%). CONCLUSIONS: Telephone counselling is an important and effective resource to elicit requests that otherwise might remain hidden; therefore, it can be a useful link between the health-care system and callers. This is true mainly for men. The next step could be to establish a quality management instrument to investigate whether users find the service helpful.

A new freezing and storage procedure improves safety and viability of haematopoietic stem cells and neutrophil engraftment: a single institution experience.

BACKGROUND AND OBJECTIVES: Autologous peripheral blood stem cell transplantation has recently become a standard therapeutic approach to virus-related or infected haematological malignancies. Collection, manipulation, storage and thawing of leukapheresis products in this subset of patients require strict monitoring to prevent infection risk for operators and risk of contamination for other stored bags. MATERIALS AND METHODS: This is a non-randomized retrospective observational study. In the 2000-2002 period, a single bag freezing procedure was used for autologous peripheral blood stem cell transplantation. Bags were stored in tanks containing liquid and gas phase nitrogen. In 2002, the processing procedure was revised, and a second additional safety bag and a new storage tank containing jacketed liquid nitrogen have been used. RESULTS: A total of 524 bags were thawed, of which 121 processed with the single bag method and 403 with the double bag method. Forty-nine and 109 patients were infused respectively. The observed rupture rate with the single bag in liquid and gas phase nitrogen was 17 and 2.5%, respectively, against a rupture rate as little as 0.24% with the new methodology. Viability revealed levels of 84.4% +/- 6.1% and 96.9% +/- 2.4% for the single and double-bag respectively. This statistically significant (P < 0.0001) difference correlated with better neutrophil engraftment. CONCLUSIONS: The new proposed method, based on a double bag and storage freezer without liquid or gas phase nitrogen into a cryogenic chamber, significantly reduces bag rupture and bio-hazard and improves stem cell viability and neutrophil engraftment remarkably.

Plasma HHV-8 viral load in HHV-8-related lymphoproliferative disorders associated with HIV infection.

This is a mono-institutional analysis of the clinical features, immunological and virological findings, and prognostic factors of patients with HIV infection and HHV-8-lymphoproliferative disorders. Patients with Multicentric Castleman Disease and HHV-8-related lymphoma diagnosed and treated from April 1987 to June 2004 were included in the study. HHV-8 and HIV plasma viral load, CD4+ count, hematologic parameters, and general wellbeing (performance status) were assessed at the onset of the diseases and analyzed in order to identify possible prognostic factors. Nine patients with Multicentric Castleman disease, and 16 with HHV-8-related lymphomas (13 primary effusion lymphomas and 3 solid lymphomas), were diagnosed and treated out of 327 HIV-related non-Hodgkin's lymphomas. Four patients with Multicentric Castleman disease received only antiretroviral drugs; 5 HAART plus oral etoposide. Nine patients with primary effusion lymphoma were treated with a CHOP-like regimen (Cyclophosphamide, Prednisone anthracyclines, Vinca alkaloids, Bleomycin, Etoposide) and HAART; 1 with etoposide and HAART, 1 with HAART alone. The patients with solid lymphoma underwent CHOP-like chemotherapy. Patients with Multicentric Castleman disease showed lower median values of HHV-8 viral load and longer overall survival compared with HHV-8-related lymphomas. Patients with viral load of HHV-8, >40,000 cp/ml had a significant shorter overall survival. In the univariate analysis, HHV-8-related lymphoma, HHV-8 viral load >40,000 cp/ml and performance status >2 were associated with an increased risk of death. Multivariate analysis confirmed the diagnosis of lymphoma as an independent predictor of shorter survival.

Monthly ibandronate suppresses serum CTX-I within 3 days and maintains a monthly fluctuating pattern of suppression.

UNLABELLED: Bone turnover markers such as serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) can be used to assess drug efficacy in osteoporosis. This study evaluated the pattern of CTX-I suppression in postmenopausal osteoporotic women receiving ibandronate. Ibandronate decreased serum CTX-I levels within 3 days of therapy initiation. Over 6 months, the levels remained suppressed below baseline. INTRODUCTION: This randomized, double-blind, placebo-controlled study evaluated the rapidity of onset and pattern of suppression of the bone resorption marker serum CTX-I in women with postmenopausal osteoporosis (PMO) who received once-monthly oral ibandronate. METHODS: Women diagnosed with PMO received once-monthly oral ibandronate (150 mg) or placebo for 6 months. Serum CTX-I was measured at baseline and after study dose administration on day 3 (month 1 only) and days 7, 14, 21, and 28 (months 1-6). Bone-specific alkaline phosphatase was measured on days 7 and 28 (months 1-6). RESULTS: This study enrolled 67 women: 49 received ibandronate, 17 received placebo, and one took no study drug. At day 3, median reduction in serum CTX-I from baseline was 70.2% with ibandronate and 6.0% with placebo (difference, -64.2%; 95% confidence interval, -80.3% to -46.2%; p < 0.0001). In women receiving ibandronate, serum CTX-I levels remained consistently below baseline, exhibiting a regular monthly fluctuating pattern of suppression over 6 months. Ibandronate was well-tolerated. CONCLUSIONS: Monthly ibandronate decreased serum CTX-I within 3 days. Over 6 months, in women receiving once-monthly ibandronate, serum CTX-I remained suppressed below baseline. A monthly fluctuation, related to time from last dose, was observed.

A novel DXA-based hip failure index captures hip fragility independent of BMD.

Capability of a novel dual-energy X-ray absorptiometry (DXA)-based hip failure index (HiFI) to discriminate between hip fracture cases and controls was evaluated. Given the constraints of planar DXA, the femoral neck was assumed a foam-filled ( approximately trabecular bone), thin-walled ( approximately cortical bone) sandwich structure, while HiFI estimated the critical force sufficient to buckle the wall of such a structure. Proximal femur DXA data from 1379 women aged 65yr and older, 268 with prior hip fracture were used. Comparison between standard areal bone mineral density (BMD), femur strength index (FSI), and HiFI was based on areas under receiver operatoring characteristic curves (AUC). The mean femoral neck BMD (SD) was 0.689 (0.109) g/cm(2) among the cases and 0.768 (0.119) g/cm(2) among the controls; the mean FSI 1.33 (0.36) and 1.54 (0.41), and the mean HiFI -0.28 (0.14) and -0.18 (0.15), respectively; all intergroup differences were highly significant (p<0.001). The intergroup difference for HiFI remained significant (p<0.002) after adjusting for age and BMD or FSI. The AUCs were 0.696 (95% confidence interval [CI]: 0.661-0.730) for BMD, 0.665 (0.630-0.700) for FSI, and 0.701 (0.666-0.736) for HiFI. In conclusion, HiFI may capture structural traits that account for femoral neck fragility independently of BMD or FSI. Obviously, the use of actual geometric and structural information from three-dimensional imaging of the femoral neck would help diminish the crude assumptions of the present DXA approach and reveal the true potential of the HiFI approach to gauge hip fragility and identify at-risk individuals for hip fractures.

Recent thymic emigrants in lymphoma patients with and without human immunodeficiency virus infection candidates for autologous peripheral stem cell transplantation.

Signal joint T cell receptor excision circles (sjTRECs) have been reported as a clinical marker to measure the potential for recovery of the immune system after immunosuppressive treatments. The aim of this study was to investigate the thymic regenerative potential in 55 human immunodeficiency virus (HIV)-1 infected (HIV(+)) and non-infected (HIV(-)) lymphoma patients, candidates for autologous stem cell transplantation (ASCT). Moreover, the possible associations between sjTRECs and other immunological and clinical parameters were examined. SjTRECs levels in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction and T lymphocyte subsets were analysed by flow cytometry. Our data showed that sjTRECs were reduced in lymphoma patients compared to healthy controls, although a weak significant association between low sjTRECs levels and increasing age was maintained [odds ratio (OR) = 4.00; 95% confidence interval (CI) 1.09-17.17]. We found that different chemotherapeutic treatments seem to induce similar effects on the thymic reservoir, independently from their intensity (type and number of cycles of previous chemotherapy). Results from multivariate models including adjustment for patients' sex, type of lymphoma and type of chemotherapy showed that thymic output was independent from HIV infection (OR, 0.95; 95% CI 0.20-4.48). SjTRECs levels correlated with naive T cell subsets in overall lymphoma patients and after stratification by HIV infection (r > 0.37). HIV replication should be maximally suppressed to properly evaluate thymic output by sjTREC markers. Our results suggested that de novo T cell generation is maintained partially in pretreated recurrent lymphoma patients, candidates for ASCT, and could contribute to restore the immune function after transplantation.