Lineare und nichtlineare optische Eigenschaften von asymmetrischen Nanostrukturen und Oligomeren

Im Rahmen der Arbeit wurden asymmetrische Nanostrukturen und Oligomere hergestellt und optisch charakterisiert. Diese plasmonischen Nanostrukturen fungieren als optische Antennen für sichtbares Licht und weisen wie ihre makroskopischen Pendants ein Nah- und Fernfeld auf. Der Fokus der Arbeit richtete sich auf die optische Untersuchung schräger konischer Nanostrukturen sowie von Oligomeren, die aus einzelnen radial bzw. azimutal angeordneten Nanostäbchen bestehen. Im Rahmen des Projektes wurde die Geometrie eines schrägen Nanokegels als geeignete Geometrie zur parallelen Nahfeldverstärkung vieler einzelner Nanostrukturen identifiziert und zwei Herstellungsprozesse entwickelt. Die optischen Eigenschaften der Nanostrukturen wurden mittels Transmissionsspektroskopie sowie nichtlinearer Raster-Scan-Mikroskopie charakterisiert. So konnte gezeigt werden, dass die schrägen Nanokegel das transversale Fernfeld in eine longitudinale Plasmonenschwingung umwandeln und das elektrische Nahfeld an deren Spitze verstärken. Dies ermöglicht eine kompakte Bauweise von Sensoren auf Basis der präsentierten Nanostrukturen. Des Weiteren wurde das Kopplungsverhalten von radial und azimutal angeordneten Nanostäbchen untersucht. Dazu wurden die Oligomere mittels radial und azimutal polarisierten Lasermoden angeregt und die nichtlinearen optischen Eigenschaften untersucht. Es zeigte sich, dass im Falle der radialen Oligomere die SHG-Intensität mit der Stäbchenzahl zunimmt, während für die azimutalen Oligomere mit immer kleiner werdenden Abständen zwischen den Stäbchen die SHG im Fernfeld verstummt. Dies ist auf ein Zusammenspiel der Verschiebung der Resonanzpeaks der Oligomere, der Abschwächung des Nahfeldes zwischen den einzelnen Stäbchen und der destruktiven Interfenz im Fernfeld zurückzuführen. Zum Abschluss werden erste Ergebnisse zur geometrischen Manipulation von Nanokegeln mittels eines fokussierten Heliumionenstrahls präsentiert. Darauf aufbauend ist es möglich, plasmonische Nanostrukturen auf der sub-5nm Skala zu bearbeiten und in-situ den Prozess zu kontrollieren. Dies ermöglicht eine exakte Optimierung der Geometrie auf die gewünschten Nahfeld- bzw. Fernfeldeigenschaften der optischen Antennen

Challenges and progress in the vaccination against COVID-19 in Latin America and the Caribbean

Latin American and the Caribbean (LAC) has been severely affected by the COVID-19 pandemic; vaccination joins interventions to address this serious public health crisis. To date, the health authorities of many LAC countries have issued emergency authorization to use 6 different vaccines with proven efficacy and safety, and several more vaccines are in phase 3 clinical trials. Two months into the campaigns, most of the post-vaccination reactions that have been reported have been mild or moderate. However, progress in vaccination campaigns has been very uneven among LAC countries. Among the challenges faced in the region are: insufficient global production; weaknesses in national health systems and corruption; as well as distrust of vaccines, fueled by the disinformation epidemic.La región de Latinoamérica y el Caribe (LAC) ha sido afectada severamente por la pandemia de COVID-19; la vacunación se suma a las intervenciones para hacer frente a esta grave crisis de salud pública. A la fecha, las autoridades sanitarias de numerosos países de la LAC han emitido autorización de emergencia para utilizar 6 vacunas distintas con eficacia y seguridad comprobadas, y varias vacunas más se encuentran en ensayos clínicos fase 3. Después de dos meses de iniciadas las campañas, la mayor parte de reacciones posteriores a la vacunación que se han reportado han sido leves o moderadas. No obstante, el avance en las campañas de vacunación ha sido muy desigual entre los países de LAC.  Entre los retos que se enfrentan en la región están: la insuficiente producción  global; debilidades de los sistemas de salud nacionales y la corrupción; así como la desconfianza sobre las vacunas, alimentada por la epidemia de desinformación.La región de Latinoamérica y el Caribe (LAC) ha sido afectada severamente por la pandemia de COVID-19; la vacunación se suma a las intervenciones para hacer frente a esta grave crisis de salud pública. A la fecha, las autoridades sanitarias de numerosos países de la LAC han emitido autorización de emergencia para utilizar 6 vacunas distintas con eficacia y seguridad comprobadas, y varias vacunas más se encuentran en ensayos clínicos fase 3. Después de dos meses de iniciadas las campañas, la mayor parte de reacciones posteriores a la vacunación que se han reportado han sido leves o moderadas. No obstante, el avance en las campañas de vacunación ha sido muy desigual entre los países de LAC.  Entre los retos que se enfrentan en la región están: la insuficiente producción  global; debilidades de los sistemas de salud nacionales y la corrupción; así como la desconfianza sobre las vacunas, alimentada por la epidemia de desinformación

The regulation, assessment, and management of medical devices in Mexico: How do they shape the quality of delivered healthcare?

Background: Policies for health technologies such as medical devices are essential and contribute to improved quality of healthcare. The regulation, assessment, and management represent important functions of medical devices. Insufficiently developed interactions between these functions impact the quality of delivered healthcare. To date studies lack to analyse these functions in a broad way. The aim of this study is to analyse the regulation, assessment, and management of orthopaedic medical devices in Mexico and how they shape healthcare. Methods: This qualitative study included 42 stakeholders involved directly or indirectly in the regulation, assessment, or management for orthopaedic medical devices in Mexico. Results: The fragmentation of responsibilities for medical device functions may be a central aspect of our findings concerning challenges reported by interviewees. Strengthening technovigilance based on improved reporting across health care institutions emerged as pathway to improve medical device regulation. With regard to improving the medical device assessment, a comprehensive update of the standard list represents a relevant opportunity. Integrating advanced quality attributes into procurement processes regarding decision-making, purchasing strategy, and procurement agent is needed to fostering the management. Conclusions: This study provides a broad analysis of medical device functions within a health system and highlights in this specific context how improvements might be achieved. It addresses a broad range of interest groups represented by policy makers, health service providers, managers and administrators of healthcare facilities, and doctors with an interest in health technologies. In this paper we highlight important themes that influence outputs and outcomes of the regulation, assessment, and management and discuss strategies in fostering these areas. To date, the regulation, assessment, and management of medical devices are rarely analysed in a broad way, even though these functions importantly contribute to the successful implementation of health technology policies. The quality of delivered healthcare is influenced by the performance between and within these functions. In Mexico, little discussion has been raised on challenges of the regulation, assessment, and management of medical devices. Changes to current processes and practices can improve outputs and outcomes of these functions and positively influence the quality of delivered healthcare. Stakeholder involvement and commitment is essential to this

Antibiotics in Mexico: An analysis of problems, policies, and politics

The inappropriate use of antibiotics poses a risk to individual health, is a waste of health resources, and triggers antibiotic resistance, a global health problem. Despite strategies promoted internationally to address antibiotic misuse and resistance (AMR), few low and middle-income countries have fully incorporated them into their national health policies. There is scarce research on the factors that affect the development of AMR policies at the national level. The present study addresses this gap by applying a policy-analysis approach to understand agenda setting, policy inaction and policy change with regard to AMR, focusing on the case of Mexico. This study is designed as a longitudinal case-study, looking at events between 2001 and 2012 in Mexico, which cover two periods of government. The study used Kingdon’s multiple streams (MS) theory of agenda-setting to guide the analysis, explaining both when the issue of AMR was denied a position on the agenda (first period studied) and when the issue gained agenda status and a policy change occurred (second period studied). The methods used were semi-structured interviews with key social actors, document analysis and media analysis. The following factors hindered AMR inclusion in the health policy agenda during the 2000-2006 administration: a) low problem visibility and a narrow definition that pulled AMR away from the scope of public policies; b) lack of clarity on the policy alternatives and their feasibility; c) absence of policy entrepreneurs promoting these policies; d) within the health-reform context, improving medicine stocks was the priority. During the 2006-2012 administration, the problem of self-medication with antibiotics gained visibility when it was related to the 2009 influenza pandemic; a group of specialists acted as policy entrepreneurs supporting AMR policies. The national health crisis and a previous designation of an institutional body to control medicine sales favoured agenda placement and the development of a narrow-focused regulation, but hindered the formation of a comprehensive national policy on AMR. The usefulness of Kingdon’s theory in examining AMR agenda-setting, in the context of Mexico, is explained. The research findings are discussed in light of other studies to draw lessons for Mexico and other countries aiming to develop AMR policies

Access to cancer medicines in public hospitals in Mexico:The view of stakeholders

BACKGROUND: Access to cancer medicines is a core component of comprehensive cancer care; as such, it is included in Mexico's public health insurance: Seguro Popular de Salud (SPS). Learning about stakeholders' experiences on processes and barriers influencing access to essential cancer medicines within healthcare facilities allows identifying needed policies to improve access to cancer care. OBJECTIVE: The aim of this study was to obtain the insights of health professionals in public hospitals in Mexico on how SPS influences access to cancer medicines regarding medicine selection, financing, and procurement and supply systems. The purpose is to identify policy areas that need strengthening to improve access to cancer medicines. METHODS: Semi-structured interviews were conducted with 67 health professionals from 21 public hospitals accredited by SPS across Mexico. A framework analysis was used with categories of analysis derived from the World Health Organization's Access framework. RESULTS: Most stakeholders reported that the availability of listed cancer medicines was sufficient. However, cancer specialists reported that medicines coverage by SPS was restrictive covering only basic cancer care. Public hospitals followed SPS treatment protocols in selecting and prescribing cancer medicines but used different procurement procedures. When essential cancer medicines were unavailable (not listed or stocked-out), hospitals reported several strategies such as prescribing alternative therapies, resorting to direct purchases, and assisting patients in obtaining medicines elsewhere. Other reported barriers to access to treatment were: distance to health facilities, poor insurance coverage, and financial restrictions. CONCLUSIONS: Health professionals have encountered benefits and challenges from the implementation of SPS influencing access to cancer medicines and care in Mexico, pointing to areas in which action is necessary. Finding the right balance between expanding the range and cost of cancer treatments covered by insurance and making basic cancer care available to all is a challenge faced by Mexico and other middle-income countries

Availability, prices, and affordability of selected essential cancer medicines in a middle-income country - the case of Mexico

BACKGROUND: More alternatives have become available for the diagnosis and treatment of cancer in low- and middle-income countries. Because of increasing demands, governments are now facing a problem of limited affordability and availability of essential cancer medicines. Yet, precise information about the access to these medicines is limited, and the methodology is not very well developed. We assessed the availability and affordability of essential cancer medicines in Mexico, and compared their prices against those in other countries of the region. METHODS: We surveyed 21 public hospitals and 19 private pharmacies in 8 states of Mexico. Data were collected on the availability and prices of 49 essential cancer medicines. Prices were compared against those in Chile, Peru, Brazil, Colombia and PAHO's Strategic Fund. RESULTS: Of the various medicines, mean availability in public and private sector outlets was 61.2 and 67.5%, respectively. In the public sector, medicines covered by the public health insurance "People's Health Insurance" were more available. Only seven (public sector) and five (private sector) out of the 49 medicines were considered affordable. Public sector procurement prices were 41% lower than in other countries of the region. CONCLUSIONS: The availability of essential cancer medicines, in the public and private sector, falls below World Health Organization's 80% target. The affordability remains suboptimal as well. A national health insurance scheme could serve as a mechanism to improve access to cancer medicines in the public sector. Comprehensive pricing policies are warranted to improve the affordability of cancer medicines in the private sector

Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation

Thousands of transcriptome data sets are available, but approaches for their use in dynamic cell response modelling are few, especially for processes affected simultaneously by two orthogonal influencing variables. We approached this problem for neuroepithelial development of human pluripotent stem cells (differentiation variable), in the presence or absence of valproic acid (signaling variable). Using few basic assumptions (sequential differentiation states of cells; discrete on/off states for individual genes in these states), and time-resolved transcriptome data, a comprehensive model of spontaneous and perturbed gene expression dynamics was developed. The model made reliable predictions (average correlation of 0.85 between predicted and subsequently tested expression values). Even regulations predicted to be non-monotonic were successfully validated by PCR in new sets of experiments. Transient patterns of gene regulation were identified from model predictions. They pointed towards activation of Wnt signaling as a candidate pathway leading to a redirection of differentiation away from neuroepithelial cells towards neural crest. Intervention experiments, using a Wnt/beta-catenin antagonist, led to a phenotypic rescue of this disturbed differentiation. Thus, our broadly applicable model allows the analysis of transcriptome changes in complex time/perturbation matrices

Geometrical Defects in Josephson Junction Arrays

Dislocations and disclinations in a lattice of Josephson junctions will affect the dynamics of vortex excitations within the array. These defects effectively distort the space in which the excitations move and interact. The interaction energy between such defects and excitations are determined and vortex trajectories in twisted lattices are calculated. Finally, possible experiments observing these effects are presented.Comment: 26 pages including 5 figure

Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation.

Mutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet. Examining the muscle biopsy of our index ALS8 patient of European origin revealed globular accumulations of VAPB aggregates co-localised with autophagy markers LC3 and p62 in partially atrophic and atrophic muscle fibres. In line with this skin fibroblasts obtained from the same patient showed accumulation of P56S-VAPB aggregates together with LC3 and p62. Detailed investigations of autophagic flux in cell culture models revealed that P56S-VAPB alters both initial and late steps of the autophagy pathway. Accordingly, electron microscopy complemented with live cell imaging highlighted the impaired fusion of accumulated autophagosomes with lysosomes in cells expressing P56S-VAPB. Consistent with these observations, neuropathological studies of brain and spinal cord of P56S-VAPB transgenic mice revealed signs of neurodegeneration associated with altered protein quality control and defective autophagy. Autophagy and RBP homeostasis are interdependent, as demonstrated by the cytoplasmic mis-localisation of several RBPs including pTDP-43, FUS, Matrin 3 which often sequestered with P56S-VAPB aggregates both in cell culture and in the muscle biopsy of the ALS8 patient. Further confirming the notion that aggregation of the RBPs proceeds through the stress granule (SG) pathway, we found persistent G3BP- and TIAR1-positive SGs in P56S-VAPB expressing cells as well as in the ALS8 patient muscle biopsy. We conclude that P56S-VAPB-ALS8 involves a cohesive pathomechanism of aberrant RBP homeostasis together with dysfunctional autophagy