Return to 1616: Multispecies Fauna Reconstruction Requires Thinking Outside the Box.

Conservation translocations have become increasingly popular for 'rewilding' areas that have lost their native fauna. These multispecies translocations are complex and need to consider the requirements of each individual species as well as the influence of likely interactions among them. The Dirk Hartog Island National Park Ecological Restoration Project, Return to 1616, aspires to restore ecological function to Western Australia's largest island. Since 2012, pest animals have been eradicated, and conservation translocations of seven fauna species have been undertaken, with a further six planned. Here, we present a synthesis of the innovative approaches undertaken in restoring the former faunal assemblage of Dirk Hartog Island and the key learnings gathered as the project has progressed.

Pain relief for women undergoing oocyte retrieval for assisted reproduction.

BACKGROUND: Various methods of conscious sedation and analgesia have been used for pain relief during oocyte recovery in in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) procedures. The choice of agent has also been influenced by the quality of sedation and analgesia as well as by concerns about possible detrimental effects on reproductive outcomes. OBJECTIVES: To assess the effectiveness and safety of different methods of conscious sedation and analgesia on pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL (from their inception to present); the National Research Register and Current Controlled Trials. We searched reference lists of included studies for relevant studies and contacted authors for information on unpublished and ongoing trials. There was no language restriction. The search was updated in July 2012. SELECTION CRITERIA: Only randomised controlled trials comparing different methods of conscious sedation and analgesia for pain relief during oocyte recovery were included. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction were performed independently by two review authors. Interventions were classified and analysed under broad categories or strategies of sedation and pain relief to compare different methods and administrative protocols of conscious sedation and analgesia. Outcomes were extracted and the data were pooled when appropriate. MAIN RESULTS: With this update, nine new studies were identified resulting in a total of 21 trials including 2974 women undergoing oocyte retrieval. These trials compared five different categories of conscious sedation and analgesia: 1) conscious sedation and analgesia versus placebo; 2) conscious sedation and analgesia versus other active interventions such as general and acupuncture anaesthesia; 3) conscious sedation and analgesia plus paracervical block versus other active interventions such as general, spinal and acupuncture anaesthesia; 4) patient-controlled conscious sedation and analgesia versus physician-administered conscious sedation and analgesia; and 5) conscious sedation and analgesia with different agents or dosage. Evidence was generally of low quality, mainly due to poor reporting of methods, small sample sizes and inconsistency between the trials.Conflicting results were shown for women's experience of pain. Compared to conscious sedation alone, more effective pain relief was reported when conscious sedation was combined with electro-acupuncture: intra-operative pain mean difference (MD) on 1 to 10 visual analogue scale (VAS) of 3.00 (95% CI 2.23 to 3.77); post-operative pain MD in VAS units of 2.10 (95% CI 1.40 to 2.80; N = 61, one trial, low quality evidence); or paracervical block (MD not calculable).The pooled data of four trials showed a significantly lower intra-operative pain score with conscious sedation plus paracervical block than with electro-acupuncture plus paracervical block (MD on 10-point VAS of -0.66; 95% CI -0.93 to -0.39; N = 781, 4 trials, low quality evidence) with significant statistical heterogeneity (I(2) = 76%). Patient-controlled sedation and analgesia was associated with more intra-operative pain than physician-administered sedation and analgesia (MD on 10-point VAS of 0.60; 95% CI 0.16 to 1.03; N = 379, 4 trials, low quality evidence) with high statistical heterogeneity (I(2) = 83%). Post-operative pain was reported in only nine studies. As different types and dosages of sedative and analgesic agents, as well as administrative protocols and assessment tools, were used in these trials the data should be interpreted with caution.There was no evidence of a significant difference in pregnancy rate in the 12 studies which assessed this outcome, and pooled data of four trials comparing electro-acupuncture combined with paracervical block with conscious sedation and analgesia plus paracervical block showed an odds ratio (OR) of 0.96 (95% CI 0.72 to 1.29; N = 783, 4 trials) for pregnancy. High levels of women's satisfaction were reported for all modalities of conscious sedation and analgesia as assessed in 12 studies. Meta-analysis of all the studies was not attempted due to considerable heterogeneity.For the rest of the trials a descriptive summary of the outcomes was presented. AUTHORS' CONCLUSIONS: The evidence from this review of 21 randomised controlled trials did not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte recovery. The simultaneous use of more than one method of sedation and pain relief resulted in better pain relief than one modality alone. The various approaches and techniques reviewed appeared to be acceptable and were associated with a high degree of satisfaction in women. As women vary in their experience of pain and in coping strategies, the optimal method may be individualised depending on the preferences of both the women and the clinicians and resource availability.

Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.

PURPOSE: To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. PATIENTS AND METHODS: Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. RESULTS: Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). CONCLUSION: Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

Idiopathic granulomatous mastitis: a 25-year experience.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory condition of the breast that can mimic inflammatory breast cancer and periductal mastitis (PDM). Eighteen patients with a histopathologic diagnosis of IGM, seen over a period of 25 years, were retrospectively reviewed and compared with 133 patients with PDM and 100 normal patients. STUDY DESIGN: The unit's pathology database and clinic letters for this time period were used to identify patients who had presented with IGM. A retrospective review of the notes was used to extract reproductive factors, cigarette smoking habits, and ethnicities that were recorded at presentation. These were compared with data from a similar group of patients with PDM and a control group. RESULTS: All IGM patients were women. Median age was 36 years (range 18 to 67 years) compared with 52 years (range 20 to 77 years) for PDM patients (p < 0.001). Seventeen percent of IGM patients were smokers at the time of presentation, as compared with 60% of PDM patients (p < 0.001). Although parity was similar for all groups, 10 IGM patients (56%) had given birth in the last 5 years, compared with 6 (5%) PDM patients (p < 0.001) and 20 (20%) in the control group (p=0.0194). Two IGM patients had recurrences after pregnancy. The course of IGM varied from 11 to 105 weeks and was not affected by any treatment modalities. CONCLUSIONS: IGM patients are younger, have given birth more recently, and are less likely to be Caucasian as compared with PDM patients. IGM is not related to smoking and can recur. Treatment should be supportive.

Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial.

PURPOSE: To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor-positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization. RESULTS: Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile. CONCLUSION: Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.

Conscious sedation and analgesia for oocyte retrieval during IVF procedures: a Cochrane review.

BACKGROUND: Various methods of sedation and analgesia have been used for pain relief during oocyte recovery during IVF. OBJECTIVE: To compare conscious sedation and analgesia with alternative methods for pain relief and pregnancy outcomes. METHODS: We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the National Research Register and Current Controlled Trials up to February 2004. RESULTS: Twelve trials were included. Owing to considerable heterogeneity, regarding types and dosages of sedation or analgesia used, and tools used to assess pain, a meta-analysis was attempted only in trials where appropriate data were available. Clinical pregnancy rates per woman in individual trials were comparable. Data on pain showed conflicting results. CONCLUSION: No single method or delivery system appeared superior for pregnancy rates and pain relief. Future studies need to be consistent in the choice of tools used to measure pain and the timing of such evaluations.

Analgesia for labour pain--analysis of the trends and associations in the Grampian region of Scotland between 1986 and 2001.

BACKGROUND: Although intrapartum analgesia has been in use since Victorian times, there have been few attempts to study its usage from routinely collected data. This population based epidemiological study aimed to analyse retrospective data on the distribution of different types of labour analgesia used by women in the Grampian region of Scotland between 1986 and 2001 in order to examine time trends and associations. METHODS: Data records on all deliveries occurring in the years 1986 to 2001 were extracted from the Aberdeen Maternity and Neonatal Databank. The rates of the use of epidural, opioid and Entonox or no analgesia for pain relief in labour in each year were calculated. Maternal, pregnancy, labour and delivery characteristics were compared among the users of three different analgesics by univariate and multivariate analyses. RESULTS: A total of 81,418 deliveries were analysed. Of these, 12,659 (15.5%) women had epidural, 33,819 (41.5%) had used opioids and 26,974(33.1%) received either Entonox or no analgesia at all. The women who received epidural analgesia were younger, shorter and heavier and had larger babies (OR = 1.05, 95% CI 1.01, 1.08). Three quarters of them were primigravidae and had longer periods of gestation. They were also more likely to have suffered pregnancy related complications (OR = 2.11, 95% CI 1.8, 2.4). Labour was more likely to have been induced (OR = 2.8, 95% CI 2.6, 2.9) and to have lasted longer in this group of women. Women in this group were 5 times more likely to have an instrumental delivery (95% CI 4.9, 5.1) and 7 times more likely to have a Caesarean section (95% CI 5.7, 9.3). CONCLUSION: Non epidural analgesia was found to be the most popular choice for pain relief in labour in the Grampian region between 1986 and 2001, although an increase in the uptake of epidural services is starting to occur. The type of labour analgesia used is associated with the epidemiological characteristics of the women's pregnancy, labour and delivery.

Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.

INTRODUCTION: The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/- 0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. CONCLUSION: Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.

Costs and benefits of a one stop clinic compared with a dedicated breast clinic: randomised controlled trial.

OBJECTIVE: To determine the cost to the NHS and the impact on anxiety of a one stop clinic for assessing women with suspected breast cancer. STUDY DESIGN: Randomised controlled trial. PARTICIPANTS: Women aged 35 or over referred with a breast lump. STUDY SETTING: Teaching hospital, north west England. INTERVENTIONS: Women were randomly allocated to attend a one stop clinic or a dedicated breast clinic. OUTCOME MEASURES: Reduction in mean anxiety from baseline at 24 hours after the first visit and at 3 weeks and 3 months after diagnosis; mean cost per patient. RESULTS: 670 women were randomised. Compared with women who attended the dedicated clinic, patients attending the one stop clinic were less anxious 24 hours after the visit (adjusted mean change in state anxiety _5.7 (95% confidence interval _8.4 to _3.0)) but not at 3 weeks or 3 months after diagnosis. The additional cost to the NHS of a one stop attendance was pound 32 per woman; this was largely explained by greater cytopathological and radiological staff costs. CONCLUSION: One stop clinics may not be justified in terms of a reduction in short term anxiety.