Foi realizada traqueostomia e colocação de sonda de gastrostomia

Foi realizada traqueostomia e colocação de sonda de gastrostomia percutânea transendoscópica (PEG), pelo método de Ponski-Gauderer (pull method). O exame endoscópico efetuado durante o procedimento não revelou lesões na mucosa gástrica ( fig. 1). Três meses mais tarde,

o doente recorreu ao serviço de urgência por presença de conteúdo hemático na sonda de gastrostomia. Foi realizada endoscopia digestiva alta, que revelou múltiplas lesões vegetantes na parede anterior do estômago, adjacentes ao botão interno da PEG, algumas das quais ulceradas (Figura 2 and Figura 3). O exame histológico das biopsias efetuadas mostrou tratar-se de um carcinoma pouco diferenciado, sendo a análise imuno-histoquímica consistente com metastização de carcinoma da laringe, com elevada expressão

de citoqueratina CK34B12 e baixa GSK1120212 manufacturer expressão de citoqueratinas CK8/18. Em neoplasias do trato aerodigestivo superior, a gastrostomia percutânea endoscópica é frequentemente utilizada para suporte nutricional. O método de Ponski-Gauderer (pull method) foi inicialmente descrito para a colocação da PEG e é o mais amplamente utilizado. Neste método, a sonda de gastrostomia passa através da boca, faringe e esófago antes de atingir a parede abdominal. A disseminação tumoral ou metástases no local da PEG é uma complicação rara com o pull method (0,7 a 2%) 1. Existe uma grande variedade de teorias acerca do mecanismo de propagação, sendo o mais provável a sementeira direta 17-AAG order durante a passagem do dispositivo, pelo cisalhamento de células tumorais 2 and 3. Em 2007, uma revisão dos casos publicados tentou identificar Tangeritin os fatores de risco associados à disseminação tumoral e desenvolver estratégias para minimizá-lo4. Os fatores patológicos identificados incluíram: localização

faringoesofágica da neoplasia primitiva, fatores relacionados com a histologia da lesão (tipo pavimento-celular e pouco ou moderadamente diferenciado), estadio patológico avançado e lesão primária de grandes dimensões ao diagnóstico. No que diz respeito a fatores de risco relacionados com a terapêutica, estes incluíram: colocação de PEG por via endoscópica, utilização do pull method, tumor primário não tratado e intervalo superior a 3 meses após colocação inserção da PEG. Embora o risco metastização pelo trato de PEG seja pequeno, devem ser tomadas precauções especiais durante o procedimento. A opção por métodos de inserção do tubo de gastrostomia que não necessitem da sua passagem através da faringe, minimizando o contacto direto com as células tumorais, deverá ser tomada em consideração. Os métodos alternativos de colocação de PEG incluem opções com apoio endoscópico, radiológico (guiado por ecografia ou fluoroscopia) ou cirúrgico (mini-laparotomia ou laparoscopia).

Hybridization of single-cell WGA products to DNA microarrays or S

Hybridization of single-cell WGA products to DNA microarrays or SNP arrays allows uncovering copy number changes in the cell. SNP arrays provide

a distinct advantage as copy number calls can be integrated with B allele fractions of SNPs and with genotype calls [31], thus also allowing the discovery of copy neutral LOH changes in a cell [32 and 33], or even to haplotype its entire genome [34 and 35]. Despite the use of ultra-high resolution array platforms and the development of state-of-the-art computational and statistical Androgen Receptor Antagonist order methods, the majority of array-based methods can only reliably detect copy number changes encompassing millions of bases in a solitary cell [36, 37, 38• and 39]. The main difficulty is to distinguish a genuine copy number change from a local allelic WGA artefact due to %GC-bias, ADO or VX-809 in vitro PA events [28]. In addition, the cell-cycle stage of the isolated cell can complicate the analysis as cells in S phase can have 2, 3 or 4 copies for a diploid locus, leading to false

structural DNA-imbalance discoveries [40]. Remarkably, a recent study reported the detection of copy number alterations as small as 56 kb in single-cell PCR WGA products hybridized to 180 K oligo-arrays [41]. Array profiling of single cells has been applied to study the biology of CTCs [42••] and DTCs [38• and 39]. Heitzer et al. used the technology to profile genetic relationships between primary colorectal

carcinomas, metastases and CTCs derived from the same patients [ 42••]. Although CTCs shared a number of gains and losses with the primary tumour and/or the metastasis, interestingly, they also observed private copy number changes in CTCs as well as heterogeneity between CTCs. Such results are paving the way for using CTCs as a liquid biopsy to guide clinical decision-making. Decitabine Sequencing of single-cell WGA-products recently improved the resolution of a cell’s DNA-copy number profile by algorithmic focal sequence-read depth analyses [16, 17••, 27•• and 43] (Figure 3b). Ni et al. [ 44••] demonstrated that copy number aberration patterns of CTCs in different patients with the same lung cancer subtype can be extraordinarily similar, but dissimilar when compared to copy number landscapes of CTCs in patients with different lung cancer subtypes, and thus be of diagnostic significance. Furthermore, driven to understand intra-tumour cell population structure and genome evolution in breast cancer, Navin and colleagues [ 16 and 17••] developed single-nucleus sequencing for copy number profiling of single cancer cells able to detect alterations with a resolution of 54 kb on average. By phylogenetic analyses, they could infer common ancestors, clonal expansions and divergence of subpopulations. Genome-wide profiling of structural variation in a single cell is still in its infancy.

To more accurately assess the uPA-associated alterations in the i

To more accurately assess the uPA-associated alterations in the inflammatory response after DSS-induced colonic mucosa injury, we examined the colon Ibrutinib mw of mice at an early time point after DSS treatments, i.e., 1 week

after the last DSS cycle. We found that DSS-treated mice presented foci of colonic dysplastic glands, which in the long term have been reported to evolve to neoplasia through a well-characterized sequence of events [33], [45] and [46]. We hypothesized that preneoplastic lesions in the colon of uPA−/− + DSS mice may have thrived and evolved into well-sized polyps due to a particular tumor-promoting inflammatory milieu. At 1 week after DSS treatment, we found that uPA−/− + DSS and WT + DSS mice had numerous dysplastic lesions in comparable numbers. However, uPA deficiency Trichostatin A purchase significantly correlated with a more advanced grade of the dysplastic lesions. This finding co-existed with a more robust infiltration of neutrophils and macrophages and an inflammatory response characterized by significantly elevated levels of pro-inflammatory cytokines, such as TNF-α, IL-17, and especially IL-6. The concomitant elevation of the anti-inflammatory cytokine IL-10 was evidently unable

to downregulate these inflammatory cells and cytokines, which have been shown to promote carcinogenesis in the colon and other sites Dapagliflozin [6], [7], [9], [53] and [64]. The uPA−/− + DSS mouse colitis was also different from the one in WT + DSS mice in that it exhibited less T-lymphocytes in the ulcerative lesions and the remaining colonic lamina propria and more in the organized lymphoid tissue of the bowel. Likewise, the Foxp3 + suppressive

subset of T-lymphocytes (Treg) followed a similar pattern. This finding suggests that T-lymphocytes and Treg accumulate in the organized lymphoid bowel tissue and MLN of uPA−/− + DSS mice, but their translocation in the damaged mucosa is retarded. This is probably due to their reduced mobility because of the altered cell–extracellular matrix interactions caused by the lack of uPA-mediated proteolysis [11] and [61]. Our findings regarding Treg are interesting, given the debated role of this immune-suppressive subset of lymphocytes in carcinogenesis [53], [65] and [66]. Indeed, the roles of Treg in cancer appear paradoxical. Studies correlating high densities of tumor-associated Treg with poor prognosis in several types of human cancers are now challenged by studies on the same types of cancer demonstrating correlation with longer survival of patients [67], [68], [69], [70], [71] and [72].

The current in the receiving coil can then be transformed into a

The current in the receiving coil can then be transformed into a power source for the implanted hardware or data signals can be extracted. Several

limiting factors in this approach complicate the design of wireless stimulating implants of any kind, neural prostheses included. The first is that the most efficient transfer of electromagnetic energy between the selleck compound primary and secondary coils occurs when the coils directly appose each other; physical separation and misalignment therefore impose an efficiency penalty due to the “uncoupling” of the transmitting and receiving coils (Rasouli and Phee, 2010). In particular, rapid reductions in power transfer efficiency are seen with relative angles >20° between the transmitting and receiving coils (Ng et al., 2011). This is particularly find more problematic for retinal implants, in which eye movement may require the use of additional coil pairs to ensure consistent coupling (Ng et al., 2011). In a cortical prosthesis the implanted electrode arrays may be self-contained, including inductive coils for power and data transmit/receive (Lowery, 2013 and Rush et al., 2011), or the power/data transfer electronics and coil may be separate from the arrays themselves (Coulombe et al., 2007). An advantage of the self-contained

array approach is the lack of any requirement for tethering, which may reduce damage to the cortex from relative motion of the brain and arrays in the long term (see Section 6.3.1). However, a disadvantage of the self-contained coils is the variation in coupling between the individual implanted array coils and the external coil. For example, arrays implanted on the medial surface of the occipital pole may be at a greater angle to the transmitting coil than those on the more lateral surface. Furthermore, if arrays are implanted more anteriorly onto medial calcarine cortex, these would be more distant from, and orthogonal to the external coil than the more

superficial arrays, resulting in poor or zero coupling and energy transfer. Aside from tethering medial arrays to a more superficially-mounted Morin Hydrate coil, alternatives may include the aforementioned optical or ultrasonic approaches to power and/or data transfer. Another consideration in the use of wireless power and data transfer derives from the absorption of electromagnetic energy by tissue, which increases exponentially with frequency (Al-Kalbani et al., 2012); the need to transfer sufficient power while maintaining high data transfer rates therefore introduces competing constraints that complicate the design process. Moreover, the separate wire coils used for data and power transfer can interfere with each other, introducing complexity to the design of receiving hardware (Kiani and Ghovanloo, 2014 and Rush et al., 2011).

In addition to the respiratory tract tissues, the following organ

In addition to the respiratory tract tissues, the following organs were fixed, processed, and histopathologically examined to clarify whether long-term MS inhalation induced any extra-pulmonary carcinogenesis by in this PFT�� solubility dmso model: both adrenal glands, aorta abdominalis, bone (os femoris with joint), bone marrow (cervical, thoracic,

sternum, lumbar, os femoris), brain (cerebrum, cerebellum, brain stem, hippocampus, paraventricular parts), caecum, diaphragm, ductus thoracicus, both epididymes, eye with optic nerve, gall bladder, gross lesions observed, Harderian glands, heart (left and right ventricle, septum), small intestine (duodenum, jejunum, ileum), large intestine (colon, rectum), both kidneys and ureters, both lacrimal glands (infraorbitalis, extraorbitalis), liver, lymph nodes (axillary, bronchial, cervical, inguinal, mandibular, mediastinal, mesenteric, paraaortic, poplietus), mammary gland, mucosa (mouth), muscle (skeletal), nerve (sciatic), esophagus, olfactory bulb, both ovaries and the mesovarium, see more pancreas, pituitary, both preputial glands, prostate, salivary glands (submandibular, parotid), both seminal vesicles, skin, spleen, sternum, stomach and forestomach, both testes, thymus, both thyroids (including parathyroids), tissue masses or tumors, tongue (inclusive base), urethra, urinary bladder, uterus (including cervix and

both uterine horns and oviducts), and vagina. Histopathological Interleukin-2 receptor preparations of respiratory tract organs were performed at Philip Morris Research Laboratories GmbH, Cologne, Germany. The histopathological evaluation was performed by Histovia GmbH, Overath, Germany. All pulmonary proliferative lesions were classified according to international classifications and criteria (Brambilla et al., 2001 and Dungworth

et al., 2001). Histopathological preparations of non-respiratory tract organs were performed by the Laboratory of Pharmacology and Toxicology GmbH & Co KG, Hamburg, Germany. The histopathological examination was performed by Toxicologic Pathology Consultancy (Kiel, Germany). Classification of neoplastic lesions in the various organs except the lungs was performed (according to the criteria defined by Mohr, 2001). All histopathological examinations were performed without knowledge of the treatment groups. Gene expression analysis was performed on lung tumor samples from the MS-300 and sham control groups. Frozen sections (20 μm) from whole lung tissue were placed on sterilized glass slides and stained with cresyl violet. Total tissues from single lung tumors were collected from these slides using laser capture micro-dissection (Zeiss, Oberkochen, Germany) except of one slide, which was preserved for the histopathological characterization of the tumor. The tumor tissues were immediately lysed with Qiazol lysis buffer (Qiagen, Hilden, Germany).

Screenees: 1027 of 1032 (>99%) colonoscopy screenees who complete

Screenees: 1027 of 1032 (>99%) colonoscopy screenees who completed both knowledge and attitude items had adequate knowledge; 915 (89%) colonoscopy screenees also had a positive Erismodegib in vitro attitude; 815 of 824 (99%) CT colonography screenees who completed both items had adequate knowledge and 742 (90%) also had a positive attitude. Non-screenees: 675 of 698 (97%) colonoscopy non-screenees had adequate knowledge, 344 (49%) also had a negative attitude.

Of the 192 responding CT colonography non-screenees, 180 (94%) had adequate knowledge and 94 (49%) also had a negative attitude. Non-screenees often had adequate knowledge and a positive attitude toward screening: 47% of responding colonoscopy non-screenees (331/698) and 45% of responding CT colonography non-screenees

(86/192). Our study shows that a large majority of colonoscopy and CT colonography screenees make informed decisions about taking part in a population-based colorectal cancer screening program, compared to about half of responding non-screenees. Both in the colonoscopy and in the CT colonography almost half of the responding non-screenees had adequate knowledge and a positive attitude, suggesting the existence www.selleckchem.com/products/bmn-673.html of additional barriers to participation. Our study has several strengths. Data were collected in a large pilot colorectal cancer screening program, designed as a randomized trial. All invitations were sent in the same time period, minimizing external influences through Ponatinib purchase general public awareness. The information leaflets of both examinations were identically designed where appropriate and all screenees received a standardized consultation to inform them about the entire screening procedure.

At the time of our study, the Netherlands did not have a population-based colorectal cancer screening program. The decision to participate in a randomized trial, such as this one, differs from the decision to participate in a population-based screening program. It is very well possible that the willingness to participate in a trial does not perfectly translate into the willingness to take part in a more widely announced national screening program. As such, the proportions observed in our study do not unconditionally apply to population-based screening programs in general. We should also mention that the definition of informed decision making as defined by Marteau et al. is not perfect. In decision-making about screening there may be predictable barriers to participation, like expected burden and immobility of an invitee, and unpredictable barriers, such as an acute illness, which might result in differences between intended and actual behavior [37]. We defined adequate knowledge as correct responses to more than half of the knowledge items, an arbitrary cut-off.

The contributions of Maria Amaya, Megha Desai, Shou Zhen Wang, Sh

The contributions of Maria Amaya, Megha Desai, Shou Zhen Wang, Sheng Zu Zhu, and many past students and fellows to the work done in the author’s laboratory is gratefully acknowledged. The helpful Omipalisib mouse assistance of Amy Jones in preparation of this manuscript is most appreciated. “
“Naoaki Harada, Juan Zhao, Hiroki Kurihara, Naomi Nakagata, and Kenji Okajima Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus. Translational Research 2011;158:106–17 In the August 2011 issue of Translational Research, we found that figures 4A∼4I were incorrect. Thus, we

replaced these figures by correct ones. Authors regret this error and apologize for any confusion Depsipeptide mw and inconvenience it may have caused. Figure options Download full-size image Download high-quality image (474 K) Download as PowerPoint slide “
“We wish to acknowledge the outstanding contributions of our reviewers and Editorial Advisory Board during the past year. The quality and breadth of the Journal is only made

possible by the dedicated efforts of our reviewers. Fadi Akar Ziyad Al-Aly Conrad Alano Lori Altshuler Ana Andreazza Laura Andreoli George Asare Arif Asif Veronika Bachanova Jeehyeon Bae Bryan Becker David Beer Chris Benson Lars Berglund Sangeeta Bhorade Darell Bigner Matthew Bilodeau Philip Binkley Markus Bitzer Istvan Boldogh James Bonner Carol Bradford Camille Brasselet George Brewer Nils Brunner Steve Brunwasser Roy Calne Andrew Campbell Haris Carageorgiou Jose Cavazos Edgar Charles Lee-Young Chau Jorge Chavarro Min Chen Matthew Ciorba Paolo Colombo Gyorgy Csako Massimo Cugno Glenn Cunningham

Louis D’Alecy Hiranmoy Das Yvonne Datta Daniel De Backer Elfride De Baere Hiram Dokainish Nicholas Donato J. Downey Liqin Du Warwick Dunn Richard Effros Oliver Eickelberg Scott Ely Philip Factor Susan Fagan Denis Feliers Aaron Fischer Steven Fisher Aime Franco Nikolaos Frangogiannis Sophia Frangou Ken Freedland Panfeng Fu Crystal Gadegbeku Luciano Gattinoni Lois J. Geist MycoClean Mycoplasma Removal Kit Jian-Guo Geng Jon George Ioannis Georgiou William Gerthoffer Sourav Ghosh Don Gibbons Scott Gitlin Ben Glaser Harry Goldsmith Dmitry Gregoryev Thomas Gremmel David Gretch Helena Gylling Joel F. Habener Pavel Hamet Anne Hamik Jean Hartley Khaled Hassan Derek Hausenloy Charles Heilig J. F. Hejtmancik Donald Henderson Norah Henry Pedro Hernandez-Cortes Chaim Hershko Helen Heslop Jay Hess Karen Hirschi Jacqueline Ho Walter Horl Joanna-Marie Howes C. P. Hu Richard Hurwitz Allan Jaffe Edward N. Janoff Eijiro Jimi Min Joo Ravi Kalhan Mike Kapiloff Yousuf Karim Reena Kartha B. S.

The F verticillioides colonies on each plate were counted to det

The F. verticillioides colonies on each plate were counted to determine the number of CFUs per gram of root and/or stem. DsRed-labeled fungus- and mock-inoculated roots were sampled at 24, 48, 72, 96 and 144 h after inoculation (HAI), ground using a mortar and a pestle, and then mixed in 10 ml of acetonitrile/water (1:1, V/V) containing 5% formic acid. The mixture was shaken vigorously on a rocker shaker (220 r min− 1) for 3 h [32] to disrupt the fungal colonies prior to incubation. The extracts were diluted 1000-fold with acetonitrile/water (3:7, V/V) containing 1% formic acid and diluted samples were subjected to competitive ELISA using a Beacon

FB1 plate kit (Portland, OR, USA). The absorbance of samples was read at 450 nm with a fluoremeter RT-6000 (Rayto Life and Analytical Sciences Co., Ltd., Shenzhen, China). F. verticillioides is sensitive to the pH of maize roots buy Ceritinib which can affect its growth and metabolism. To determine the pH of maize roots inoculated with the DsRed-labeled fungus, roots (0.5 g) were sampled from plants at 144 h after inoculation, ground, and suspended in 5 ml of deionized water. A standard pH electrode (VWR Scientific, West Chester, PA, USA) was used to determine the pH of each sample. Analysis of total starch in root was performed by the amyloglucosidase/α-amylase method (AOAC method 996.11) with the total starch assay kit from Megazyme

(Wicklow, Ireland). Three samples were MAPK Inhibitor Library analyzed for each maize line as replicates. The experiments for parameter determination were carried out twice. Analysis of variance (ANOVA) was performed using PROC GLM procedure in SAS statistical package (version 9.1, SAS Institute, Cary, NC, USA). Treatment means were compared by Duncan’s multiple-range test (P < 0.05). Wild type of F. verticillioides was co-cultured with A. tumefaciens cells containing the target gene DsRed to generate DsRed-labeled fungal strains.

After three rounds of selection on hygromycin B-containing PDA, hygromycin B-resistant transformants were subjected to epifluorescent microscopic observation. Flucloronide Using the gene-specific primers, amplification of DNA confirmed the integration of DsRed gene in the genome of the wild type. Based on analyses of mitotic stability of DsRed protein expression, growth rates of colonies, and metabolism of extracelluar enzymes, i.e., protease, cellulase, amylase and pectase, strain FVR-12 was used in the study because it resembled the wild type for most of the characteristics examined (data not shown). The susceptible maize line B73 and resistant line Qi 319 were infected with F. verticillioides strain expressing DsRed through root inoculation. The conidia germinated on the root surfaces of both lines at 24 HAI. On line B73 the fungus formed runner hyphae ( Fig. 1-a). The quantity of hyphae colonized on B73 was greater than that on Qi 319 ( Fig. 1-b and c).

, 2010 and Robinson et al , 2010) and TMS to this region selectiv

, 2010 and Robinson et al., 2010) and TMS to this region selectively impairs semantic task performance when control demands are high (Whitney, Kirk, et al., 2011 and Whitney et al., 2012). The semantic control hypothesis predicts that this area should show increased activation for abstract relative to concrete words (referred to hereafter as an A > C effect) because their variable meanings require greater executive regulation.

check details A > C effects have been reported in IFG (Binder et al., 2009 and Wang et al., 2010) but they have not been linked specifically to executive control demands. Other researchers have suggested instead that IFG is involved in representing logical propositions that are key to the meaning of abstract concepts (Shallice & Cooper, 2013) or in integrating or “unifying” semantic knowledge of a word with prior context (Hagoort, 2005). Although most research has focused on the role of left IFG in semantic control, recent studies suggest that other regions, including posterior middle temporal gyrus, are also involved in this function (Noonan et al., 2010, Whitney, Jefferies, et al., 2011 and Whitney,

Kirk, et al., 2011). In contrast, the anterior temporal lobes1 (ATL) are associated with the representation of semantic knowledge. ATL involvement in multi-modal conceptual knowledge has been observed in studies using H2O-PET (Sharp et al., 2004 and Vandenberghe et al., 1996), distortion-corrected fMRI (Binney et al., 2010 and Visser and Lambon Ralph, 2011), MEG (Marinkovic et al., 2003) and rTMS (Pobric et al., 2007 and Pobric et al., 2010). It is demonstrated most strikingly in the learn more syndrome of semantic dementia, in which atrophy to this area results in selective yet progressive and eventually profound impairment to verbal and non-verbal semantic knowledge (Bozeat et al., 2000 and Patterson et al., 2007). According to the representational substrates perspective, areas of ATL specialised for representing verbal aspects of knowledge should show an A > C effect while the reverse should be true for areas specialised selleck chemicals llc for representing visual object properties. In other words, the likelihood of observing

concreteness effects in the ATL should depend on the degree to which portions of this brain region are specialised for verbal versus visual processing. Some parts of the ATL do show graded specialisation of this sort. The superior ATL shows greater activation for semantic processing of auditory and verbal stimuli, relative to pictures (Moore and Price, 1999, Visser et al., 2012 and Visser and Lambon Ralph, 2011). This specialisation may arise because this area is strongly connected to primary auditory processing regions in posterior STG (Binney, Parker, & Lambon Ralph, 2012). Consistent with the idea that abstract words are especially dependent on verbal processing regions, A > C effects have been observed in this area in previous studies (Binder et al., 2009, Noppeney and Price, 2004, Tettamanti et al.

The request by authorities to remove thiomersal caused fear among

The request by authorities to remove thiomersal caused fear amongst the general public concerning the toxicity of vaccine components, and negatively impacted overall vaccine uptake and acceptance. In the subsequent years, following authority guidance, vaccine manufacturers have removed thiomersal from most paediatric vaccines and reduced the amount of thiomersal in the few remaining vaccine formulations in a common effort to remove mercury from vaccines and re-establish public confidence in immunisation programmes. However, the WHO acknowledges that making changes to the thiomersal content of licensed

vaccines containing this preservative is a complex issue requiring careful consideration. Any change in the formulation of thiomersal-containing vaccines may

LDK378 in vivo have an important impact on the quality, safety and efficacy of the vaccine Selleckchem PCI-32765 and therefore any decision regarding the elimination or reduction of thiomersal in vaccines should be based on a demonstrated adverse effect. New-generation vaccines are subject to increased safety testing throughout the vaccine development process. The safety assessment has been enhanced throughout preclinical, clinical and post-licensure studies. All safety assessments performed have the objective of increasing the likelihood of identifying possible safety concerns and consequently of taking the necessary measures to remove or minimise them. Available data indicate that licensed vaccines have a benefit–risk profile where the benefits clearly surpass the risks. This short overview of vaccine development processes and post-licensure surveillance describes how clinical development and assessment of vaccines is constantly improving and evolving. It also illustrates else how changes to the processes over time have helped to

generate the robust data needed to enhance the benefit–risk profiles of new vaccines. There is now a large number of diseases for which licensed vaccines are available (Appendices, Supplementary Table 6), however, we are still faced with challenges in the form of diverse populations and complex pathogens; these require further novel approaches to antigen selection, manufacture, presentation and delivery. The main areas of new vaccine research are the subject of Chapter 6 – Vaccines of the future. “
“Key concepts ■ New tools are available to aid vaccine manufacturers in meeting challenges for new vaccine development □ Many technologies that are already available continue to be improved, including adjuvants and novel vaccine delivery platforms The advances made in vaccine technology since Edward Jenner vaccinated the young James Phipps against smallpox have had a spectacular impact on human health over the last two centuries (see Chapter 1 – Vaccine evolution).