Informal sale of antibiotics in Guatemalan convenience stores before and after implementation of federal antibiotic dispensing legislation.

BACKGROUND: Convenience stores in Guatemala provide essential consumer goods in communities, but many dispense antibiotics illegally. Federal legislation, passed in August of 2019, requires prescriptions for antibiotic purchase at pharmacies but it is unclear if this legislation is enforced or if it has any impact on unlawful sales of antibiotics. METHODS: To determine if antibiotic availability changed in convenience stores, we carried out a repeated measures study collecting antibiotic availability data before and after implementation of the dispensing regulation. RESULTS: There was no statistical difference in the proportion of convenience stores that sold antibiotics before and after antibiotic regulations [66.6% (295/443) and 66.7% (323/484), respectively, P>0.96], nor in the number of stores selling amoxicillin [55.5% (246/443) and 52.3% (253/484), respectively, P>0.96], but fewer stores (20%) sold tetracycline capsules after regulation was passed (P<0.05). For stores visited both before and after passage of legislation (n=157), 15% stopped selling antibiotics while 25% started selling antibiotics. Antibiotics from convenience stores were reportedly sold for use in people and animals. CONCLUSIONS: Antibiotics remain widely available in convenience stores consistent with no significant change in the informal sector after implementation of prescription requirements for pharmacies. Importantly, effects from regulatory change could have been masked by potential changes in antibiotic use during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic.

Defunctioning stoma in rectal cancer surgery - A risk factor for Low Anterior Resection Syndrome?

BACKGROUND: In rectal cancer surgery the formation of a defunctioning stoma is common in order to reduce the consequences of an anastomotic leakage. The role of a defunctioning stoma and time to stoma reversal, in relation to major Low Anterior Resection Syndrome (LARS) in the long-term perspective, is still unclear. The aim of the study was to investigate the association between a defunctioning stoma and long-term bowel function. METHOD: Patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm county, Sweden, who had no history of anastomotic leakage, without a remaining stoma, free of cancer and alive in April 2017 were eligible for the study. The exposures were (i) use of defunctioning stoma at cancer surgery and (ii) time to stoma reversal. Main outcome was major LARS with information retrieved from the LARS score questionnaire. Multivariable logistic regression model was used to calculate odds ratios (OR) primary comparing major LARS to no LARS. RESULTS: A total of 430 patients were included in analysis. The mean follow-up time was 6.7 years after surgery (range 3.4-10.7 years). The use of a defunctioning stoma was associated to major LARS with an adjusted OR of 2.43 (95% CI 1.14-5.20) when compared to no stoma. There were no evident associations between time to stoma reversal and the risk of major LARS. CONCLUSION: This study indicates that the presence of a defunctioning stoma is associated with impaired bowel function in the long-term perspective, while failing to show any clear association to time to stoma reversal.

Effect of root canal irrigant (sodium hypochlorite & saline) delivery at different temperatures and durations on pre-load and cyclic-loading surface-strain of anatomically different premolars.

AIM: To evaluate the effect of NaOCl (5%) and saline (control) irrigant delivery at different temperatures and durations on pre-load and cyclic-loading tooth-surface-strain (TSS) on anatomically different premolars. METHODOLOGY: Single-rooted premolars (n = 36), root-canal-prepared in standard manner, were randomly allocated to six irrigation groups: (A1) NaOCl-21 °C; (A2) NaOCl-60 °C; (A3) saline-21 °C then NaOCl-21 °C; (A4) saline-60 °C then NaOCl-21 °C; (A5) saline-21 °C then NaOCl-60 °C; (A6) saline-60 °C then NaOCl-60 °C. A1-2 received nine 10-min irrigation periods (IP) with NaOCl; A3-6 received nine 10-min IP with saline, followed by 9 IP with NaOCl at different temperature combinations. Premolars (n = 56) with single, fused or double roots prepared by standard protocol, were stratified and randomly allocated to: (B1) saline-21 °C; (B2) saline-80 °C; (B3) NaOCl-21 °C; (B4) NaOCl-80 °C. TSS (µÑ”) was recorded pre-irrigation, post-irrigation and pre-load for each IP and during cyclic loading 2 min after each IP, over 30-274 min, using strain-gauges. Generalised linear mixed models were used for analysis. RESULTS: Baseline TSS in double-rooted premolars was significantly (p=0.001) lower than in single/fused-rooted-premolars; and affected by mesial-wall-thickness (p=0.005). There was significant increase in loading-TSS (µÑ”) after NaOCl-21 °C irrigation (p=0.01) but decrease after NaOCl-60 °C irrigation (p=0.001). TSS also increased significantly (p = 0.005) after Saline-80 °C irrigation. Pre-load "strain-shift" was noted only upon first saline delivery but every-time with NaOCl. Strain-shift negatively influenced loading-TSS after saline or NaOCl irrigation (A3-6) but was only significant for saline-21 °C. CONCLUSIONS: Tooth anatomy significantly affected its strain characteristics, exhibiting limits within which strain changes occurred. Intra-canal introduction of saline or NaOCl caused non-random strain shifts without loading. Irrigation with NaOCl-21 °C increased loading tooth strain, as did saline-80 °C or NaOCl-80 °C but NaOCl-60 °C decreased it. A "chain-link" model was proposed to explain the findings and tooth biomechanics.

Prevalence of low anterior resection syndrome and impact on quality of life after rectal cancer surgery: population-based study.

BACKGROUND: The prevalence of major low anterior resection syndrome (LARS) after rectal cancer surgery varies from 17·8 to 56·0 per cent, but data from high-quality studies are sparse. The aim of this study was to determine the prevalence of LARS and its association with quality of life (QoL) in a large, well defined, population-based cohort. METHODS: This was a population-based study that included all patients who had curative rectal cancer surgery with total or partial mesorectal excision in Stockholm County in Sweden between 2007 and 2013. Patients without a remaining stoma, free from cancer and alive in April 2017 were eligible for the study. The LARS score questionnaire, EORTC QLQ-C30 and Cleveland Clinic Florida Fecal Incontinence score were used as outcome measures. Adjusted mean scores (and differences) of EORTC QLQ-C30 for LARS groups were calculated using repeated measures ANCOVA regression models while adjusting for predefined confounders. RESULTS: In total, 481 patients (82·6 per cent response rate) were included in the analysis. Mean follow-up time was 6·7 (range 3·4-11·0) years after surgery. The prevalence of LARS was 77·4 per cent (370 of 478 patients), with 53·1 per cent (254 of 478) experiencing major LARS. Patients with major LARS reported worse on all EORTC QLQ-C30 subscales (except for financial difficulties) than patients without LARS. A higher mean LARS score was associated with a greater impact on bowel-related QoL. CONCLUSION: After anterior resection for rectal cancer, the majority of patients suffer from major LARS with a negative impact on QoL.

ANTECEDENTES: La prevalencia del síndrome de resección anterior baja (Low Anterior Resection Syndrome, LARS) mayor después de cirugía del cáncer de recto varía entre 17,8% y 56,0%, pero los datos procedentes de estudios de alta calidad son escasos. El objetivo de este estudio fue determinar la prevalencia de LARS y su asociación con la calidad de vida (quality of life, QoL) en una gran cohorte poblacional bien definida. MÉTODOS: Este fue un estudio de base poblacional con todos los pacientes que se sometieron a cirugía curativa de cáncer de recto con exéresis total o parcial del mesorrecto en el condado de Estocolmo en Suecia entre 2007-2013. Los pacientes sin estoma definitivo, sin recidiva y vivos en abril de 2017 fueron elegibles para el estudio. El cuestionario de puntuación LARS, el EORTC QLQ-C30 y el sistema de puntuación de incontinencia de la Cleveland Clinic Florida se usaron como medidas de resultado. Las puntuaciones medias ajustadas (y las diferencias) de EORTC QLQ-C30 para grupos LARS se calcularon utilizando modelos de regresión ANCOVA de medidas repetidas ajustando por factores de confusión predefinidos. RESULTADOS: En total, 481 pacientes (tasa de respuesta del 82,6%) se incluyeron en el análisis. El tiempo medio de seguimiento fue de 6,7 años después de la cirugía (rango 3,4-11,0 años). La prevalencia de LARS fue 77,4% (n = 370) y un 53,1% (n = 254) presentó un LARS mayor. Los pacientes con LARS mayor tuvieron peores resultados en todas las subescalas EORTC QLQ-C30 (excepto por dificultades financieras) que los pacientes sin LARS. Una puntuación LARS media más alta se asoció con un mayor impacto en la calidad de vida relacionada con el intestino. CONCLUSIÓN: Después de una resección anterior por cáncer de recto, la mayoría de los pacientes sufren un LARS mayor con un impacto negativo en la calidad de vida.

Population-based study of surgical treatment with and without tumour resection in patients with locally recurrent rectal cancer.

BACKGROUND: Population-based studies of treatment of locally recurrent rectal cancer (LRRC) are lacking. The aim was to investigate the surgical treatment of patients with LRRC at a national population-based level. METHODS: All patients undergoing abdominal resection for primary rectal cancer between 1995 and 2002 in Sweden with LRRC as a first event were included. Detailed information about treatment, complications and outcomes was collected from the medical records. The patients were analysed in three groups: patients who had resection of the LRRC, those treated without tumour resection and patients who received best supportive care only. RESULTS: In all, 426 patients were included in the study. Of these, 149 (35·0 per cent) underwent tumour resection, 193 (45·3 per cent) had treatment without tumour resection and 84 (19·7 per cent) received best supportive care. Abdominoperineal resection was the most frequent surgical procedure, performed in 65 patients (43·6 per cent of those who had tumour resection). Thirteen patients had total pelvic exenteration. In total, 63·8 per cent of those whose tumour was resected had potentially curative surgery. After tumour resection, 62 patients (41·6 per cent) had a complication within 30 days. Patients who received surgical treatment without tumour resection had a lower complication rate but a significantly higher 30-day mortality rate than those who underwent tumour resection (10 versus 1·3 per cent respectively; P = 0·002). Of all patients included in the study, 22·3 per cent had potentially curative treatment and the 3-year survival rate for these patients was 56 per cent. CONCLUSION: LRRC is a serious condition with overall poor outcome. Patients undergoing curative surgery have an acceptable survival rate but substantial morbidity. There is room for improvement in the management of patients with LRRC.

Radiation Field Strengths Near Cylindrical Volume Sources Via Point-source Correction Factors.

Due to the ease with which the radiation field strength is determined for a point source, the field strength emanating from radiopharmaceutical therapy patients is sometimes estimated by using the point source approximation with a correction factor. It is inevitable that the correction factor will occasionally be used under conditions that do not precisely match those for which the factor was originally derived. The difficulty is that the boundary of the correction factor's domain of acceptability is usually unclear. The purpose of this paper is to address this issue. The patient is modeled as a cylinder containing the radionuclide administered to the patient. From first principles, the expression for converting the radiation field strength of an unshielded point source to that of the extended cylindrical volume source is derived. This expression is analytically separated into the component depicting geometric dispersion of the source material into the volume and the component depicting self-absorption (absorption characteristics of I in water are used). These components, along with their composite, are presented showing their dependence on patient size, distance from the patient, and various dispersion patterns of the source material within the patient. Correlation of theory and measurement is demonstrated, and a conceptual grasp is conveyed regarding field strength variations around volume sources with changes in shape, size, distance, and other parameters. Using data presented, the radiation field strength emanating from a radiopharmaceutical therapy patient can be estimated from the point source approximation and customized for patient size and presumed internal radionuclide distribution.

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-ß3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.

Preoperative CT-based predictive factors for resectability and medium-term overall survival in patients with peritoneal carcinomatosis from colorectal cancer.

AIM: To determine preoperative radiological findings that may correlate with resectability and medium-term overall survival (OS) in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC). MATERIALS AND METHODS: The study included 81 consecutive patients with PC scheduled for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). PCI scores from preoperative computed tomography (CT) were compared with Peritoneal Cancer Index (PCI) scores at laparotomy. Odds ratio (OR), a Cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed to evaluate resectability ("open and close procedure" [O&C]) and OS. RESULTS: A radiological PCI score ≥20 (OR; 20.61 p=0.001), involvement of the perihepatic region (OR; 3.63, p=0.047) and extensive small bowel involvement (OR; 9.90, p=0.019) were risk factors for O&C. Involvement of the left abdominal region correlated adversely to OS (HR; 6.86, p<0.001). CONCLUSIONS: The location of PC, in addition to the extent of PC as determined by preoperative CT, predicts resectability and medium-term survival.

Risk factors for anastomotic leakage following ileosigmoid or ileorectal anastomosis.

AIM: Reconstruction with an ileosigmoidal anastomosis (ISA) or ileorectal anastomosis (IRA) is a surgical option after a subtotal colectomy. Anastomotic leakage (AL) is a problematic complication and high rates have been reported, but there is limited understanding of the risk factors involved. The aim of this study was to assess the established and potential predictors of AL following ISA and IRA. METHOD: This was a retrospective cohort study including all patients who had undergone ISA or IRA at three Swedish referral centres for colorectal surgery between January 2007 and March 2015. Data regarding clinical characteristics, treatment and outcome were collected from medical records. Univariate and multivariate logistic regression models were used to determine the association between patient and treatment related factors and the cumulative incidence of AL. RESULTS: In total, 227 patients were included. Overall, AL was detected amongst 30 patients (13.2%). Amongst patients undergoing colectomy with synchronous ISA or IRA (one-stage procedure), AL occurred in 23 out of 120 (19.2%) compared with seven out of 107 (6.5%) after stoma reversal with ISA or IRA (two-stage procedure) (P = 0.004). In addition, the multivariate analyses revealed a statistically significantly lower odds ratio for AL following a two-stage procedure (OR 0.10, 95% CI 0.03-0.41, P = 0.001). CONCLUSIONS: This study confirms high rates of AL following ISA and IRA. In particular, a synchronous procedure with colectomy and ISA/IRA carries a high risk of AL.

Population-based study of factors predicting treatment intention in patients with locally recurrent rectal cancer.

BACKGROUND: Local recurrence of rectal cancer (LRRC) is associated with poor survival unless curative treatment is performed. The aim of this study was to investigate predictive factors for treatment with curative intent in patients with LRRC. METHODS: Population-based data for patients treated for primary rectal cancer between 1995 and 2002, and with LRRC reported as first event were collected from the Swedish Colorectal Cancer Registry and medical records. The associations between patient-, primary tumour- and LRRC-related factors and intention of the treatment for LRRC were determined. The impact of the identified predictive factors on prognosis after treatment with curative intent was also assessed. RESULTS: A total of 426 patients were included in the study, of whom 149 (35·0 per cent) received treatment with curative intent. Factors significantly associated with treatment of the LRRC with palliative intent were primary surgery with abdominoperineal resection (odds ratio (OR) 5·16, 95 per cent c.i. 2·97 to 8·97), age at diagnosis of LRRC at least 80 years (OR 4·82, 2·37 to 9·80), symptoms at diagnosis (OR 2·79, 1·56 to 5·01) and non-central location of the LRRC (OR 1·79, 1·15 to 2·79). The overall 5-year survival rate was 8·9 per cent for all patients and 23·1 per cent among those treated with curative intent. In patients treated with curative intent, factors associated with increased risk of death were age 80 years or more (hazard ratio (HR) 2·44, 95 per cent c.i. 1·55 to 3·86), presence of symptoms (HR 1·92, 1·20 to 3·05), non-central tumour location (HR 1·51, 1·01 to 2·26) and presence of hydronephrosis (HR 2·02, 1·18 to 3·44). CONCLUSION: Non-central location of the LRRC, presence of symptoms and age at least 80 years at diagnosis of the LRRC were associated with treatment with palliative intent.

An Excel-Based System to Manage Radiation Safety for the Family of Patients Undergoing 131I Therapy.

The purpose of this study was to develop spreadsheet workbooks that assist in the radiation safety counseling of 131I therapy patients and their families, providing individualized guidelines that avoid imposing overly conservative restrictions on family members and others. Methods: The mathematic model included biphasic patient radionuclide retention. The extrathyroidal component was a cylindric volume with a diameter corresponding to the patient's size and included patient self-absorption, whereas the thyroidal component was a point source whose transmission was reduced by self-absorption. A separate model in which the thyroid, extrathyroid, and bladder compartments fed serially from one to the next was developed to depict the radionuclide levels within the patient and to estimate the activity entering the environment at each urination. Results: The system was organized into a set of 4 workbooks: the first to be used with ablation patients prepared using thyrogen, the second with ablation patients prepared by deprivation, the third with hyperthyroid patients, and the fourth with the unusual hyperthyroid patient who finds the restrictions to be oppressive and returns 5-10 d after administration for a measurement and reassessment. The workbooks evaluated the radiation field strength external to the patient and indicated restrictions based on selected dose limits. To assist physicians in suggesting contamination precautions, the workbooks also evaluated the radioactivity present within the patient and the estimated discharge into the environment as a function of time. Conclusion: The workbooks that were developed assist the radiation safety counselor in individualizing radiation protection procedures for the family of patients undergoing 131I therapy. The workbook system avoids overly conservative assumptions while permitting selection of appropriate dose limits for each individual.

The 5-amino acid N-terminal extension of non-sulfated drosulfakinin II is a unique target to generate novel agonists.

The ability to design agonists that target peptide signaling is a strategy to delineate underlying mechanisms and influence biology. A sequence that uniquely characterizes a peptide provides a distinct site to generate novel agonists. Drosophila melanogaster sulfakinin encodes non-sulfated drosulfakinin I (nsDSK I; FDDYGHMRF-NH2) and nsDSK II (GGDDQFDDYGHMRF-NH2). Drosulfakinin is typical of sulfakinin precursors, which are conserved throughout invertebrates. Non-sulfated DSK II is structurally related to DSK I, however, it contains a unique 5-residue N-terminal extension; drosulfakinins signal through G-protein coupled receptors, DSK-R1 and DSK-R2. Drosulfakinin II distinctly influences adult and larval gut motility and larval locomotion; yet, its structure-activity relationship was unreported. We hypothesized substitution of an N-terminal extension residue may alter nsDSK II activity. By targeting the extension we identified, not unexpectedly, analogs mimicking nsDSK II, yet, surprisingly, we also discovered novel agonists with increased (super) and opposite (protean) effects. We determined [A3] nsDSK II increased larval gut contractility rather than, like nsDSK II, decrease it. [N4] nsDSK II impacted larval locomotion, although nsDSK II was inactive. In adult gut, [A1] nsDSK II, [A2] nsDSKII, and [A3] nsDSK II mimicked nsDSK II, and [A4] nsDSK II and [A5] nsDSK II were more potent; [N3] nsDSK II and [N4] nsDSK II mimicked nsDSK II. This study reports nsDSK II signals through DSK-R2 to influence gut motility and locomotion, identifying a novel role for the N-terminal extension in sulfakinin biology and receptor activation; it also led to the discovery of nsDSK II structural analogs that act as super and protean agonists.

Distinct expression of interleukin (IL)-36α, ß and γ, their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease.

Interleukin (IL)-36α, IL-36ß and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36ß and IL-38 mRNA, was induced and correlated with IL-1ß and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, ß, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1ß, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1ß and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68⁺ macrophages, dendritic/Langerhans cells and CD79α⁺ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36ß and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio.

Versatile optical laser system for experiments at the European X-ray free-electron laser facility.

We present the main features of the final prototype of a pulsed optical laser, developed for pump-probe and other experiments in conjunction with the femtosecond x-ray beams at the European X-ray free-electron laser facility. Adapted to the temporal x-ray emission pattern of the facility, the laser provides 10 Hz bursts of up to 600 µs duration with intra-burst pulse frequencies as high as 4.5 MHz. In this mode, we have generated pulses as short as 12 fs at 350 W average power during the burst and with beam qualities close to the diffraction limit. This is, to the best of our knowledge, the highest power to date of a few-cycle laser operating at a center wavelength of 800 nm. Important for experimental flexibility, the laser can be configured in various unique ways, enabling, e.g., energy scaling to >3 mJ per pulse through a frequency change down to 100 kHz and the generation of nearly transform limited pulses between 12 fs and 300 fs. In addition to the 800 nm femtosecond beam line, a synchronized long pulse (0.8 ps or 400 ps) 1030 nm beam can be utilized, offering up to 4 kW burst average power, i.e. up to 40 mJ per pulse at 100 kHz. Efficient nonlinear wavelength conversion and tuning through intrinsic and external means further enhance the capabilities of the laser.

Remaining cancer cells within the fibrosis after neo-adjuvant treatment for locally advanced rectal cancer.

AIM: To analyse the incidence and distribution of remaining cancer cells within the fibrosis induced by preoperative chemo-radiotherapy (CRT) for locally advanced rectal cancer. METHODS: The histopathological specimens from 46 patients operated on with extensive surgery for locally advanced rectal cancer after CRT were examined. The extension of fibrosis in relation to the mesorectal fascia (MRF) and the distribution of cancer cells within the fibrosis was examined using routine haematoxylin-eosin staining. In addition, immunohistochemical staining with CK20 was done to examine if cancer cells were missed by routine pathological work up. RESULTS: All specimens showed CRT induced fibrosis. Two specimens showed complete response without viable cancer cells (ypT0). The fibrosis was limited inside the MRF in three cases, adherent to or involved the MRF in ten cases and in 33 cases the fibrosis was obvious outside as well as inside the fascia. Twenty-one cases showed fibrosis on the surgical resection margin, and in 9 of these cancer cells were found on the surgical margin (R1, R2-resection). 37 patients had R0 resections and among those 24 showed fibrosis beyond the MFR and 13 had scattered cancer cells in the fibrosis along or outside the MRF. CONCLUSIONS: The rate of remaining cancer cells within the fibrosis was high in patients with locally advanced rectal cancer treated with CRT. Frequently cancer cells were detected near the border of the fibrosis. A complete resection of the fibrosis is therefore recommended to achieve an R0 resection after neo-adjuvant treatment.

Non-native plants add to the British flora without negative consequences for native diversity.

Plants are commonly listed as invasive species, presuming that they cause harm at both global and regional scales. Approximately 40% of all species listed as invasive within Britain are plants. However, invasive plants are rarely linked to the national or global extinction of native plant species. The possible explanation is that competitive exclusion takes place slowly and that invasive plants will eventually eliminate native species (the "time-to-exclusion hypothesis"). Using the extensive British Countryside Survey Data, we find that changes to plant occurrence and cover between 1990 and 2007 at 479 British sites do not differ between native and non-native plant species. More than 80% of the plant species that are widespread enough to be sampled are native species; hence, total cover changes have been dominated by native species (total cover increases by native species are more than nine times greater than those by non-native species). This implies that factors other than plant "invasions" are the key drivers of vegetation change. We also find that the diversity of native species is increasing in locations where the diversity of non-native species is increasing, suggesting that high diversities of native and non-native plant species are compatible with one another. We reject the time-to-exclusion hypothesis as the reason why extinctions have not been observed and suggest that non-native plant species are not a threat to floral diversity in Britain. Further research is needed in island-like environments, but we question whether it is appropriate that more than three-quarters of taxa listed globally as invasive species are plants.

Time to local recurrence as a prognostic factor in patients with rectal cancer.

AIMS: Survival after the local recurrence of rectal cancer is influenced by several factors. The aim of this study was to ascertain whether the time interval from primary surgery for rectal cancer to local recurrence diagnosis has any impact on survival. METHODS: Population-based data was collected from the Swedish Colorectal Cancer Registry. 7410 patients were operated with radical abdominal surgery for rectal cancer during the period 1995-2002. Of these, 386 (5%) developed a local recurrence as a first event. The patients were divided into two groups: early local recurrence (ELR), diagnosed <12 months after primary surgery, and late local recurrence (LLR), diagnosed ≥12 months after primary surgery. Kaplan-Meier curves and hazard ratios were calculated for survival analyses. Survival was calculated from the date of the local recurrence diagnosis to death or end of follow-up. RESULTS: Ninety-five patients had ELR and 291 patients LLR. Median time to local recurrence was 1.7 (0.1-7.9) years. Patients with a stage III primary tumour and non-irradiated patients were more common in the ELR compared with the LLR group. Factors that influenced survival were age at diagnosis of local recurrence (p < 0.001), stage of primary tumour (p = 0.027), and surgical resection of local recurrence (p < 0.001). Time to diagnosis of local recurrence had no influence on survival. CONCLUSIONS: No difference in survival from date of diagnosis of local recurrence was seen between patients with ELR and patients with LLR. All patients with local recurrence should therefore be assessed for potential curative surgery, disregarding time to local recurrence.

High power burst-mode optical parametric amplifier with arbitrary pulse selection.

We present results from a unique burst-mode femtosecond non-collinear optical parametric amplifier (NOPA) under development for the optical - x-ray pump-probe experiments at the European X-Ray Free-Electron Laser Facility. The NOPA operates at a burst rate of 10 Hz, a duty cycle of 2.5% and an intra-burst repetition rate of up to 4.5 MHz, producing high fidelity 15 fs pulses at a center wavelength of 810 nm. Using dispersive amplification filtering of the super-continuum seed pulses allows for selectable pulse duration up to 75 fs, combined with a tuning range in excess of 100 nm whilst remaining nearly transform limited. At an intra-burst rate of 188 kHz the single pulse energy from two sequential NOPA stages reached 180 µJ, corresponding to an average power of 34W during the burst. Acousto- and electro-optic switching techniques enable the generation of transient free bursts of required length and the selection of arbitrary pulse sequences inside the burst.