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Examines safest form of breast milk for sick or premature neonates. Emphasis on risk of bacterial contamination; Impact of pasteurization on preserving antimicrobial properties; Effect of breast milk heating on supporting bacterial growth.

Abstract: Using high sensitivity differential scanning calorimetry (HSDSC), the phase transitions of dimyristoylphosphatidylcholine (DMPC) liposomal bilayers and their interaction with the model steroid beclometasone dipropionate (BDP) were found to be dependent on the method of liposome manufacture. Ethanol-based proliposomes produced liposomes having no phospholipid pretransition, a main transition of high enthalpy and a low onset temperature, and a very low incorporation of the steroid (maximum 1mol%). This was attributed to an alcohol-induced interdigitation of the bilayers, which was not apparently reversed by flushing the liposome dispersion with nitrogen in an attempt to remove ethanol. For liposomes manufactured by thin film or particulate-based proliposome methods, 1–2.5mol% steroid was optimal for incorporation within bilayers, although the nature of the steroid interaction with the bilayers differed between the two methods. For liposomes manufactured by the thin film method, a higher steroid concentration resulted in a broadened main transition and a reduced melting cooperativity. This suggests that BDP formed separate domains within the bilayers which caused non-ideal mixing and phase separation at 5mol% steroid. This observation was absent for liposomes generated from particulate-based proliposomes, indicating separate steroid domains were not formed and subsequent non-ideal mixing and phase separation did not occur. In addition, liposomes generated from particulate-based proliposomes showed reduced pretransition and main transition enthalpies. These differences were attributed to the employment of sucrose to manufacture the particulate-based proliposomes. This study has shown that the thermal behaviour of liposomes and their interaction with beclometasone dipropionate were dependent on the method of liposome manufacture. Moreover, particulate-based proliposomes may provide a reasonable alternative to the conventional thin film method in producing liposomes incorporating this steroid. [Copyright &y& Elsevier]

Bracken fern is carcinogenic when fed to domestic and laboratory animals inducing bladder and ileal tumours and is currently classified as a possible human carcinogen by IARC. The carcinogenic illudane, ptaquiloside (PTQ) was isolated from bracken fern and is widely assumed to be the major bracken carcinogen. However, several other structurally similar illudanes are found in bracken fern, in some cases at higher levels than PTQ and so may contribute to the overall toxicity and carcinogenicity of bracken fern. In this review, we critically evaluate the role of illudanes in bracken fern induced toxicity and carcinogenicity, the mechanistic basis of these effects including the role of DNA damage, and the potential for human exposure in order to highlight deficiencies in the current literature. Critical gaps remain in our understanding of bracken fern induced carcinogenesis, a better understanding of these processes is essential to establish whether bracken fern is also a human carcinogen. [ABSTRACT FROM AUTHOR]

Purpose: A positive circumferential resection margin (CRM) is regarded as a poor prognostic indicator in oesophageal cancer (OC) but its prediction can be challenging. MRI is used to predict a threatened CRM in rectal cancer but is not commonly performed in OC unlike PET/CT, which is now routinely used. Therefore, this study assessed the additional predictive value of PET-defined tumour variables compared with EUS and CT T-stage. The prognostic significance of CRM status was also assessed.Materials and Methods: This retrospective study included 117 consecutive patients [median age 64.0 (range 24-78), 102 males, 110 adenocarcinomas, 6 squamous cell carcinoma (SCC), 1 neuro-endocrine] treated between 1st March 2012 and 31st July 2015. A binary logistic regression model tested 5 staging variables; EUS T-stage (≤T2 vs ≥ T3), CT T-stage (≤T2 vs ≥ T3), PET metabolic tumour length (MTL), PET metabolic tumour width (MTW) and the maximum standardised uptake value (SUVmax).Results: The CRM was positive in 43.6%. Sixty-seven (57.3%) patients received neo-adjuvant chemotherapy (NACT), 31 patients (26.5%) underwent surgery alone and 19 patients (16.2%) had neo-adjuvant chemo-radiotherapy (NACRT). Median overall survival (OS) was 36.0 months (95% confidence interval (CI) 24.1-47.9) and the 2-year OS was 55.4%. A binary logistic regression model showed EUS ≥ T3 tumours were independently and significantly more likely to have a positive CRM than EUS ≤ T2 tumours (HR 5.188, 95% CI 1.265-21.273, p = 0.022). CT T-stage, PET MTL, PET MTW and SUVmax were not significantly associated with CRM status (p = 0.783, 0.852, 0.605 and 0.413, respectively). There was a significant difference in OS between CRM positive and negative groups (X2 4.920, df 1, p = 0.027).Conclusion: Advanced EUS T-stage is associated with a positive CRM, but PET-defined tumour variables are unlikely to provide additional predictive information. This study demonstrates the continued benefit of EUS as part of a multi-modality OC staging pathway. [ABSTRACT FROM AUTHOR]

Transparent Y 2 O 3 ceramics singly-doped with either Eu 3+ or Tm 3+ were fabricated by means of sequential consolidation steps at high pressure and temperature. These ceramics were characterized for their luminescence and thermal lensing behaviors, and the results compared to data on single crystals reported in literature. Thermal diffusivity, D , and conductivity, K , values of D =26×10 −3 cm 2 /s and K =5.8 W/m K, respectively, for 1.0 mol% Eu 3+ and 0.5 mol% Tm 3+ singly-doped Y 2 O 3 transparent ceramics were obtained. These values are about half of those for single crystal analogs. A small temperature coefficient of the optical path length change, ds / dT =3×10 −6 K −1 , was determined, making these materials suitable for applications requiring nearly athermal response. Selected spectroscopic properties were obtained by means of Judd–Ofelt analysis and together with thermal lens results provided absolute values for the fluorescence quantum efficiency of several levels, particularly 62% for the 5 D 0 level of Eu 3+ and 84% for the 3 F 4 level of Tm 3+ . [ABSTRACT FROM AUTHOR]

Abstract: Aims: The aim of this study was to determine outcomes of a reconfigured centralised upper gastrointestinal (UGI) cancer service model, allied to an enhanced recovery programme, when compared with historical controls in a UK cancer network. Materials and methods: Details of 606 consecutive patients diagnosed with UGI cancer were collected prospectively and outcomes before (n = 251) and after (n = 355) centralisation compared. Primary outcome measures were rates of curative treatment intent, operative morbidity, length of hospital stay and survival. Results: The rate of curative treatment intent increased from 21 to 36% after centralisation (P < 0.0001). Operative morbidity (mortality) and length of hospital stay before and after centralisation were 40% (2.5%) and 16 days, compared with 45% (2.4%) and 13 days, respectively (P = 0.024). The median and 1 year survival (all patients) improved from 8.7 months and 39.0% to 10.8 months and 46.8%, respectively, after centralisation (P = 0.032). On multivariate analysis, age (hazard ratio 1.894, 95% confidence interval 0.743–4.781, P < 0.0001), centralisation (hazard ratio 0.809, 95% confidence interval 0.668–0.979, P = 0.03) and overall radiological TNM stage (hazard ratio 3.905, 95% confidence interval 1.413–11.270, P < 0.0001) were independently associated with survival. Conclusion: These outcomes confirm the patient safety, quality of care and survival improvements achievable by compliance with National Health Service Improving Outcomes Guidance. [Copyright &y& Elsevier]

Abstract: Aims: Definitive chemoradiotherapy (dCRT) has been advocated as an alternative treatment for oesophageal carcinoma, but received criticism for perceived poorer locoregional disease control when compared with surgery. The aim of this study was to determine the relative incidence and pattern of oesophageal carcinoma recurrence after dCRT and surgery in patients receiving stage-directed therapy with curative intent. Materials and methods: In total, 623 consecutive patients with oesophageal carcinoma (207 squamous cell carcinoma, 416 adenocarcinoma) were studied. The primary outcome measure was disease-free survival, adjusted for baseline differences in gender, age and histological cell type. Results: Three hundred and eleven patients deemed unsuitable for surgery on the grounds of performance status (n = 137), bulky local disease (n = 121) or personal choice (n = 53) received dCRT and 312 surgery (200 received neoadjuvant chemotherapy). Oesophageal carcinoma recurrence was diagnosed in 44.1% of patients after dCRT compared with 40.7% after surgery (P = 0.222). Locoregional recurrence was more common after dCRT than after surgery (24.1% versus 9.3%, P < 0.0001). In contrast, distant metastases were more common after surgery than after dCRT (22.8% versus 12.9%, P = 0.001). The median time to recurrence in patients receiving dCRT and surgery were 15 and 17 months, respectively (P = 0.052). Stage-related disease-free 2 year survival for dCRT versus surgery was: stage I (68.6 versus 85.6%, P = 0.069), stage II (36.9 versus 47.4%, P = 0.011), stage III (31.0 versus 28.6, P = 0.878), stage IVa (21.4 versus 26.3%, P = 0.710). Conclusions: These findings provide further support for a randomised trial of dCRT versus surgery in both oesophageal squamous cell carcinoma and adenocarcinoma. [Copyright &y& Elsevier]

Abstract: Scintillation from nanoparticles is a nascent field but offers valuable fundamental insights and practical utilities. In this work, the scintillation response of LaF3:Eu nanoparticles is reported. Core/multi-shell nanoparticles were prepared using a modified solution precipitation method that takes advantage of the organic ligand ammonium di-n-octadecyldithiophosphate (ADDP) to simultaneously achieve shelling of doped core nanoparticles while avoiding agglomeration. Nanoparticles were characterized on their structure, morphology, luminescence, and scintillation behavior by means of X-ray diffraction, transmission electron microscopy, photoluminescence, and radioluminescence (RL) measurements, respectively. Analysis of the scintillation process revealed that the unique aspect of scintillation in nanoparticles when compared to bulk materials is related to the migration of carriers within the nanoparticle. Cladding of the Eu-doped core with an undoped shell was found to increase scintillation intensity by a factor of 3, and further shelling leads to a continuous decrease in RL intensity. Surface passivation, together with the decreasing probability of radiative recombination of carriers at the luminescent centers in the core with increasing number of shells grown around the core are suggested to describe the observed RL intensity behavior. Scintillation enhancement by means of shelling is a promising pathway to enhance the use of scintillator nanoparticles in detection devices. [ABSTRACT FROM AUTHOR]

Aims: To compare the outcomes of stage-directed surgical therapy and chemoradiotherapy (CRT) for oesophageal cancer and to determine if a significant age–treatment interaction exists to guide therapy. Materials and methods: Five hundred and eight consecutive patients with oesophageal cancer suitable for radical treatment based on radiological stage and performance status were studied (275 surgery; 93 surgery alone, 131 neoadjuvant chemotherapy, 51 neoadjuvant CRT and 233 definitive CRT). The primary measure of outcome was survival. Results: Thirty-day mortality rates and 2-year survival after surgery and CRT in patients <70 years were 2.4 and 57.5%, respectively, compared with 0 (P =0.207) and 47.3% (P =0.011), respectively. Thirty-day mortality rates and 2-year survival after surgery and CRT in patients ≥70 years were 7.0 and 45.1%, respectively, compared with 0 (P =0.029) and 46.3% (P =0.992), respectively. Multivariate analysis including only surgical patients in the model revealed three factors to be independently and significantly associated with survival; endoscopic ultrasound (EUS) T stage (P =0.033), EUS lymph node metastasis count (≥2 versus 0: hazard ratio 1.67, 95% confidence interval 1.06–2.92, P =0.026), and age ≥70 years (hazard ratio 1.51, 95% confidence interval 1.05–2.16, P =0.025). Conclusion: Overall survival for patients treated with surgery was strongly age dependent around the age of 70 years, and patients ≥70 years with oesophageal cancer should be aware that outcomes after CRT are similar to those after surgery. [Copyright &y& Elsevier]

Aims: To assess the strength of agreement between the perceived preoperative stage of Siewert II (oesophagogastric junction) and Siewert III (proximal gastric tumours) as determined by computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with histopathological stage. Methods: Forty-four patients with Siewert II (n =18) and III (n =26) adenocarcinomas of the oesophagogastric junction underwent preoperative CT at their local hospitals followed by specialist EUS, and the strengths of the agreement between the radiological stages and the histopathological stages were determined by the weighted Kappa statistic (Kw). Results: Kw for Siewert II T and N stages was 0.491 (p =0.016) and 0.4 (p =0.087) for CT compared with 0.852 (p =0.0001) and 1 (p =0.0001) for EUS. Kw for Siewert III T and N stages was 0.181 (p =0.206) and 0.121 (p =0.376) for CT compared with 0.173 (p =0.195) and 0.263 (p =0.031) for EUS. Conclusion: Siewert II tumour T and N stages were more accurately predicted by EUS than CT, but Siewert III tumour T and N stages were more difficult to assess, arguably because of anatomical constraints at the oesophagogastric junction. CT and EUS are complimentary techniques, and these results highlight the importance of multidisciplinary discussion in planning treatment. [Copyright &y& Elsevier]

Abstract: Aims: Paclitaxel, a radiosensitiser, has significant activity in oesophageal cancer. We aimed to conduct a feasibility study of preoperative chemoradiation using paclitaxel, cisplatin and 5-fluorouracil (5-FU). Materials and methods: Sixteen eligible patients were enrolled. Infusional 5-FU, paclitaxel and cisplatin were given for 6 weeks before and concurrent with radiation. Conformal radiotherapy was delivered in two phases (45Gy in 25 fractions). Results: A total of 62.5% of the patients experienced Grade 3–4 toxicities, 50% required admission; one patient died during the neo-adjuvant phase. Twelve (75%) patients had oesophagectomy, and two (12.5%) died after surgery. Pathological complete remission (PCR) and minimal residual disease were observed in 25% (95% CI 0.5–49.5%) and 18% (95% CI 0–38%) of patients, respectively, who underwent surgery. The median survival was 39.7 months (95% CI 15, not reached); 1-, 2-, 3-, and 4-year survivals were 75% (95% CI 56.5–99.5), 56.3% (36.5–86.7), 50% (30.6–81.6), and 50% (30.6–81.6), respectively. Conclusion: Paclitaxel, cisplatin and 5-FU (TCF)-chemoradiation is an active regimen; the current dose schedule tested is associated with unacceptable toxicity, and cannot be recommended for routine clinical use. [Copyright &y& Elsevier]

: Background and purposeRH1 is a new bioreductive agent that was developed as a cytotoxic agent with selectivity for tumour cells expressing high levels of the enzyme DT-diaphorase (DTD). The aim of the present study was to investigate the cytotoxicity of RH1 in relation to cellular levels of reducing enzymes and any interaction of RH1 with ionizing radiation under oxic and hypoxic conditions.: Patients and methodsThe MB-MDA231 human breast cancer cell line (WT) and WT cells transfected with the NQO1 gene encoding DTD (the D7 cell line) were used to examine the dependency of RH1''s cytotoxicity on cellular DTD activity. The role of the 1-electron reducing enzyme P450 reductase was also studied using a P450 reductase-transfected isogenic cell line (R4). A clonogenic assay was used to investigate the cytotoxicity of RH1 with and without irradiation in air and in nitrogen. In all cases drug exposure was for 3 h.: ResultsDTD levels were around 300-fold higher in D7 compared to WT and R4 cells. RH1 was cytotoxic at nanomolar concentrations to all the cell lines, and was 2–3 times more toxic in the D7 cells with high DTD than in the other two cell lines. Doses of RH1 was around 2-fold more effective in hypoxic than in oxic WT cells, but not by as much in D7 cells. RH1 did not radiosensitise the cells but showed an additive effect when combined with irradiation under oxic and hypoxic conditions.: ConclusionsRH1 shows high clonogenic cytotoxicity to MDA231 cells with high DTD activity but its selectivity based on the presence of DTD is much less than as shown in previous reports. RH1 showed an additive cell killing effect when combined with irradiation under both oxic and hypoxic conditions. [Copyright &y& Elsevier]

Aim: To evaluate the accuracy of contemporary N-staging and provide radiological-pathological correlation in patients with lymph node metastases (LNMs) that were radiologically staged N0.Materials and Methods: One hundred and twelve patients were included who underwent surgery alone (n=41) or neoadjuvant therapy (n=71) between October 2010 and December 2015. Contrast-enhanced computed tomography (CECT), endoscopic ultrasound (EUS), and combined positron-emission tomography (PET) and CT N-stage were compared to pathological N-stage [node-negative (N0) versus node-positive (N+) groups]. Fifty LNMs from 15 patients preoperatively staged as N0 were measured and the maximum size recorded.Results: Accuracy, sensitivity, and specificity of N0 versus N+ disease with CECT, EUS, and PET/CT was 54.5%, 39.7% and 77.3%, 55.4%, 42.6% and 75%, and 57.1% 35.3%, and 90.9%, respectively. All techniques were more likely to under-stage nodal disease; CECT (X2 32.890, df=1, p<0.001), EUS (X2 28.471, df=1, p<0.001), and PET/CT (X2 50.790, df=1, p<0.001). PET/CT was more likely to under-stage nodal disease than EUS (p=0.031). Median LNM size was 3 mm, with 41 (82%) of LNMs measuring <6 mm and 22 (44%) classified as micro-metastases (≤2 mm).Conclusion: This study has demonstrated poor N-staging accuracy in the modern era of radiological staging. Eighty-two percent of LNMs measured <6 mm, making direct identification extremely challenging on medical imaging. Future research should focus on investigating and developing alternative surrogate markers to predict the likelihood of LNMs. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Infective endocarditis due to non-toxigenic Corynebacterium diphtheriae is uncommon; we report 10 cases occurring over a 14-year period in Auckland, New Zealand and review the approach for treatment. Case series: Eight of the 10 patients had known prosthetic valves or homografts in situ. Three patients required surgical intervention for infective endocarditis. Seven patients were treated with a combination of β-lactam and aminoglycoside, and one each was treated with a combination of vancomycin and an aminoglycoside, a β-lactam alone, and vancomycin alone. All patients survived and none relapsed. Review of literature: The antibiotic treatment of 46 previously reported cases was reviewed; patients treated with a β-lactam and aminoglycoside (n =25), and without the addition of an aminoglycoside (n =11) were compared. The differences in length of treatment within each group make the comparison of outcome (mortality, need for surgical intervention, disease and treatment complications) difficult. However, regardless of the length of treatment, there was no difference in mortality or need for surgical intervention between the two groups in the currently published cases. Conclusions: Current evidence suggests that endocarditis of either native or prosthetic valves, caused by penicillin-susceptible C. diphtheriae, demonstrates a favorable outcome when treated with either a β-lactam alone or in combination with an aminoglycoside. Patient-specific factors will determine which approach is more appropriate for each individual patient. [ABSTRACT FROM AUTHOR]