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Amyloid fibril related diseases include dementia, Alzheimer’s disease and Parkinsons disease and pose an increasingly large burden to global healthcare, due to the presence of an ageing population. Despite many healthcare advances, amyloid fibril diseases remain largely untreatable, with only symptom managements available rather than any disease-modifying treatments. With hundreds of potential drug candidates failing clinical trials, this suggests that something is lacking in current approaches. One such gap is the thermodynamics of amyloid fibrils and how clinical agents modify the stability of fibrils, either positively or negatively. Thus far there has been a focus on the kinetic stability of amyloid fibrils due to the development and availability of kinetic assays. Specifically, the use of Thioflavin-T (ThT) fluorescence monitored growth curves to quantify the kinetics of amyloid growth in a robust, high-throughput manner. The equivalent thermodynamic assays are largely underdeveloped and as such remain underutilised. This thesis aims to fill this gap by developing a thermodynamic assay which can be used to quantify the Gibbs Free Energy (ΔG), enthalpy (ΔH), entropy (ΔS) and heat capacity (ΔCp) of amyloid fibril elongation. The development of this assay is detailed in Chapter 3, with the accompanying fitting script developed in Chapter 4. The assay was developed to be highly accessible in order to promote its uptake and use, with a low resource burden and a high throughput. The application of this assay to amyloid fibril systems is then detailed in chapter 5. Finally, development of a drug screening platform for use in identifying molecules which could modify the thermodynamic stability of amyloid fibrils is investigated in chapter 6. Through this thesis the development of an assay to quantify the thermodynamic stability of amyloid fibrils is described, with the stability of lysozyme, α-synuclein, insulin, tau, silk and amyloid-β fibrils investigated.

Increasing demand for clean, globally available energy, provokes the development of alternative or nonconventional energy storage sources with higher energy density and power delivery. Therefore, supercapacitors have received great attention in both academic and industrial research. In addition, supercapacitors are promising new sources of energy in the future energy technology. Hence, rapid progress has been made to understand their fundamentals and applicable aspects. Supercapacitors, also known as ultracapacitors, bridge the gap between batteries and con- ventional capacitors, which means that supercapacitors can accept and deliver charge much faster than batteries, and can store 10 to 100 times more energy per unit volume than fuel cells. Su- percapacitors are well known not only because of their huge energy density, but also due to their long shelf and good cyclic ability. The particular properties of supercapacitors are due to utiliza- tion of electrode materials with very high porosity, and also the specific mechanism of charge storage. In general, there are two fundamental chemical and physical mechanisms for energy storage. In chemical mechanism the charges are released through oxidation-reduction reaction. However, in the physical mechanism the electrical energy is stored physically with electrostatic interaction, while no chemical and phase changes occur. Hence, according to theses charge storage mechanisms supercapacitors are divided into three main groups: electric double layer capacitors (EDLCs), pseudocapacitors and hybrid capacitors. Each of these supercapacitors has its own ad- vantages and disadvantages. These three different kind of supercacaitors are distinguished by their charge storage mechanism and also their electrode materials. Electrical double layer capacitors store the charge based on physical mechanism, and also various types of carbon are used as electrode material. Pseudocapacitors save energy via electro- chemical redox reactions. Besides, these capacitors utilize metal oxides and conducting polymers as electrode material. Hybrid capacitors are another class of supercapacitors, which are constructed of two different types of electrode materials. Therefore, the mechanism of energy storage is a com- bination of both chemical and physical mechanisms. The most used electrode materials in these supercapacitors are a composition of carbon-based materials with either conducting polymers or metal oxide materials. In this work electrical double layer capacitors have captured our attention because of both their interesting energy storage mechanism and also their electrode materials. Electrode material is one of the most important factors in the performance of an electro- chemical energy storage device. Therefore, innovation of new electrode materials is one of the most attractive topics in recent investigations. Especially carbon based electrodes such as carbon nanofibers, activated carbon, carbon nanotubes (CNTs) etc. with their porous structure can pro- vide very huge surface area, consequently immense capacity. Among the examined carbon based materials carbon nanotubes are one of the most interesting because of their unique physical and chemical properties. In fact, special properties of carbon nanotubes such as individual tubular structure, very high chemical stability, low resistivity, high thermal and electrical conductivity and enormous surface area make them good candidates for electrode material in electrical double layer capacitors. Carbon nanotubes are divided into three main groups such as zigzag, armchair and chi- ral tubes. Based on their electronic structure, carbon nanotubes can have metallic or semimetallic characteristic. As mentioned above the huge capacity of carbon materials is due to their massive surface area. Furthermore, in the case of carbon nanotubes both the inner and outer walls can be available for electrolyte ions. At first it was thought, that very narrow pores do not participate in the forma- tion of double layer and energy storage. However, experimental investigations proved, that very narrow pores (lower than 1nm size) not only participate in energy storage, but also exhibit an enor- mous increase of capacitance. Later, theoretical findings showed that the image charge between ion and pore wall screen the repulsion between the ions. This leads to a denser packing of ions, consequently increasing the electrode capacitance. In this work we have studied ion intercalation into carbon nanotubes with diameters lower than 1nm as electrode material by density functional theory. All the calculations have been done using the VASP package. The idea of this work is in that we have imagined carbon nanotubes as electrode materials immersed in solution. Hence, the electrolyte ions try to penetrate into the carbon nanotubes. This work is divided into four parts, which are as follows: In the first part, we have selected truncated carbon nanotubes or carbon nanorings, whoese ends are saturated with hydrogen atoms. In particular, the truncated carbon nanotubes are include the (6,0), (8,0), (10,0) and (12,0) carbon nanotubes. As electrolyte ions alkali (Li, Na and Cs) and halogen (Cl, Br and I) atoms have been tried. Meanwhile, we have neglected the presence of solvent or any counterpart. After simulation it was realized that all the alkali atoms have lost one electron, and also the halogen atoms have obtained one more electron, and also the stable position of all the ions is in the center of the tubes. The results have shown that the surrounding tubes screen the ionic charge very effectively, thereby the ion-ion interactions are strongly reduced, which explains, why narrow tubes store charge more effectively than wider one. We have calculated the insertion energies of the atoms into the tubes and understood that for each atom the diameter of the tube has to be optimized. In the second part of the work, we extended the model of short nanotubes to infinite ones. In particular, we have chosen the (6,2)CNT, the (6,3)CNT, the (8,0)CNT and the (5,5)CNT as electrode material. Among the presented carbon nanotubes the (6,2)CNT and the (8,0)CNT are semimetallic, while the (5,5)CNT and the (6,3)CNT are metallic. Like in the previous work we have inserted alkali (Li, Na and Cs) and halogen (F, Cl, Br and I) atoms into the carbon nanotubes. The results have shown that the atoms were fully ionized. The charge exchange with the CNTs affects the band structure, and turns those tubes that were originally semiconductors into conductors. None of the ions is adsorbed chemically, their position inside the tube and their energies of adsorption are determined by a competition between electrostatic image interactions, which favor a position at the wall, and Pauli repulsion. In models for charge storage it is often assumed that in small tubes the ions are at the center, but we have found several cases where small alkali ions are positioned near the wall. We have also investigated the screening of the Coulomb potential along the axis of the tubes. In particular we wanted to see if there is a difference between semiconducting and conducting CNTs. Within the accuracy of our calculations we found no difference in the screening, because the charge transfer has made the non-chiral tubes conducting. In the third part of this work, we have investigated insertion of alkali and halogen atoms into nitrogen doped (N-doped) carbon nanotubes. Here, the (8,0)CNT and the (5,5)CNT have been chosen as electrode material. The results have shown that N-doped carbon nanotubes are less stable than the pure ones, and also the atoms were fully ionized. The position of the ions in the carbon nanotubes exhibits contradictory behavior in the (8,0)CNT than the (5,5)CNT. In fact, in the former one the ions have high repulsion from the impurity area and try to get away as far as possible. This effect is stronger in the case of small ions like Li+. However, in the (5,5)CNT the ions get closer to the nitrogen area. This behavior is caused by the difference in the spin density of carbon nanotubes. In other words, the spin density is more localized in the N-doped (8,0)CNT than the N- doped (5,5)CNT. Therefore, it causes big repulsion with the inserted ions. The nitrogen doping and charge exchange with ions affect the band structure of carbon nanotubes. Actually, substitution of nitrogen and insertion of alkali atom keep the tubes conducting. However, intercalation of halogen atoms causes both tubes to become semiconducting. We also have calculated insertion energy of ions in the N-doped carbon nanotubes. The results have shown that insertion of the ions is more favorable in the N-doped carbon nanotubes than in the pure ones. In the fourth part of the work, we have taken into account the presence of counterions. For this purpose we have tried insertion of alkali halide monomers (LiF, LiCl and NaCl), a chain of NaCl in nanotube, as well as presence of water molecules with NaCl monomer in a carbon nanotube. Therefore, the (5,5)CNT as electrode material has been chosen. In all the investigated systems, the ions and the molecules are not chemically bound to the carbon nanotube wall. In the case of alkali halide monomers there is no strong charge transfer with the nanotube. However, for the chain of NaCl this interaction is stronger, while the main charge transfer is between the alkali and halide ions in the chain. Water does not exchange charge with the nanotube. Nonetheless, it tries to hydrate the alkali and halide ions confined in the tube.

We study the effect of early life exposure to above average levels of rainfall on adult mental health. While we find no effect from pre-natal exposure, post-natal positive rainfall shocks decrease average Center for Epidemiological Studies Depression (CESD) mental health scores by 15 percent and increase the likelihood of depression by 5 percent, a more than 20 percent increase relative to the mean. These effects are limited to females. We rule out prenatal stress and income shocks as pathways and find evidence suggestive of increased exposure to disease. CINCH working paper series, vol. 2018, no. 5

Shoulder pain is a common problem with an estimated prevalence of 4% to 26%. About 1% of adults aged over 45 years consult their GP with a new presentation of shoulder pain every year in the UK. The aetiology of shoulder pain is diverse and includes pathology originating from the neck, glenohumeral joint, acromioclavicular joint, rotator cuff, and other soft tissues around the shoulder girdle. The most common source of shoulder pain is the rotator cuff, accounting for over two-thirds of cases.We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatment, topical drug treatment, local injections, non-drug treatment, and surgical treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, arthroscopic subacromial decompression, autologous whole blood injection, corticosteroids (oral, subacromial injection, or intra-articular injection), electrical stimulation, excision of distal clavicle, extracorporeal shock wave therapy, ice, laser treatment, manipulation under anaesthesia, suprascapular nerve block, non-steroidal anti-inflammatory drugs (oral, topical or intra-articular injection), opioid analgesics, paracetamol, physiotherapy (manual treatment, exercises), platelet-rich plasma injection, rotator cuff repair, shoulder arthroplasty, and ultrasound.

Strontium- and magnesium-doped lanthanum gallate (LSGM) perovskite-type compounds and doped ceria-based materials have recently been considered the most promising solid electrolytes for intermediate temperature solid oxide fuel cell (IT-SOFC) applications. While nickel metal is commonly used for the fabrication of cermet-type anodes, the rare earth nickelates, such as Sr-doped La2NiO4 (LSN), are recently developed high-performance cathode materials. For successful implementation in IT-SOFC, it is therefore essential to know the phase equilibria and thermodynamic properties for systems representing the solid electrolyte and electrode materials across their various combinations. This thesis aims to determine the phase equilibria and the thermodynamics of the relevant phases in the systems La-Sr-Ga-Mg-Ni-O, Ce-Gd-Sr-Ni-O, and Ce-Gd-La-Ni-O. Subsystems of these multi-component systems were thermodynamically modeled, based on the available literature and experimental data obtained from this work. The experimental studies were designed based on the calculated phase diagrams. A minimum number of compositions was chosen strategically to obtain a preliminary prediction of the phases in equilibrium in each constituent subsystem. Finally, the experimental and computational results were used to predict the compatibility/reactivity of IT-SOFC components under fabrication and/or operation conditions. Various experimental techniques were employed for determination of the phase equilibria such as Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX), X-ray Diffraction (XRD), Differential Scanning and Adiabatic Calorimetry, and Mass Spectrometry (MS). The CALPHAD-method (CALculation of PHAse Diagrams) and THERMOCALC software were used to obtain self-consistent sets of Gibbs energy functions. The following systems were investigated experimentally: La-Ni-O, La-Ga-Ni-O, La-Sr-Ni-O, La-Mg-Ni-O, La-Ga-Mg-Ni-O, La-Sr-Ga-Ni-O, La-Sr-Ga-Mg-Ni-O, Ce-Ni-O, Ce-Sr-O, Gd-Ni-O, Gd-Sr-O, Ce-Gd-Ni-O, Ce-Gd-Sr-O, Ce-Sr-Ni-O, Gd-Sr-Ni-O, Ce-Gd-Sr-Ni-O and Ce-Gd-La-Ni-O. Using results from this experimental work and data from the literature, the following systems were thermodynamically modeled: La-Ni-O, La-Ga-Ni-O, La-Sr-Ni-O, La-Mg-Ni-O, Ce-Ni-O, Ce-Sr-O, Gd-Ni-O and Gd-Sr-O. The systems, La-Ga-Mg-Ni-O, La-Sr-Ga-Ni-O, and Ce-Gd-Ni-O were extrapolated using parameters optimized from the constituent lower-order systems. In the La-Ni-O system, the enthalpy of formation, entropy and heat capacity of La3Ni2O7, La4Ni3O10, and LaNiO3, were determined experimentally for the first time using equilibration with the gas phase, adiabatic calorimetry and differential scanning calorimetry. In the La-Ga-Ni-O, La-Sr-Ni-O and La-Mg-Ni-O systems, extended solid solutions of La(Ga,Ni)O3, La2(Ni,Ga)O4, La4(Ni,Ga)3O10, (La,Sr)2NiO4, and La2(Ni,Mg)O4 were found, and the limits of their homogeneity ranges have been established for the first time. In addition, the compound LaNiGa11O19, with a magnetoplumbite-type structure was identified, which has not been reported in the literature to date. In the La-Ga-Mg-Ni-O system, the temperature dependence of the quasi-quaternary homogeneity range of La(Ga,Mg,Ni)O3 was determined. In the La-Sr-Ga-Ni-O system, a reaction was observed between LaGaO3 and LaSrNiO4 that formed a melilite-type La1-xSr1+xGa3O7+z, LaGaSrO4 and NiO phase. Similar reaction mechanisms were observed in the La-Sr-Ga-Mg-Ni-O system. Experiments in the Ce-Ni-O system were conducted in air as well as in a reducing atmosphere. It has been found that NiO does not react with CeO2. In the Ce-Sr-O system, the entropy and heat capacity of Sr2CeO4 were experimentally determined for the first time. In the Gd-Ni-O system a eutectic reaction was observed (liquid <=> B-Gd2O3 + NiO). The Gd-Sr-O system was modeled thermodynamically based on data from the literature and the experimentally determined homogeneity range on the Gd2O3-rich site. In the Ce-Sr-Ni-O system the solid solution of (Ce,Sr)2NiO4-z was determined. No reaction between NiO and SrCeO3 / Sr2CeO4 was found. Similarly, in the Ce-Gd-Ni-O system, no reaction was observed between (Ce,Gd)O2-z and NiO. In contrast, solid solutions of Sr(Ce,Gd)O3, Sr2(Ce,Gd)O4 and (Gd,Sr)2(Sr,Ce)O4 were determined in the Ce-Gd-Sr-O system. Also, an extended solid solution of (Gd,Sr)2NiO4 was found in the Gd-Sr-Ni-O system that does not exist in the quasi-binary sections, but is stable in higher-order systems only because a solid solution is formed. It has been also found that there is no NiO solubility in the Gd2SrO4 phase. It could be concluded that doped ceria-based materials are chemically compatible with NiO during conditions typical for both the fabrication and the operation of IT-SOFC’s, whereas LSGM-type electrolytes react with NiO under the fuel cell fabrication conditions. Moreover, although La2NiO4 is a high-performance cathode, it cannot be used in combination with LSGM- or CGO-type electrolytes, due to its reactivity with both of these materials under fabrication conditions. Strontium- und Magnesium- dotierte Lanthangallat Verbindungen des Perowskit-Typs und dotierte Ceroxid-basierte Materialien (DC) wurden kürzlich als hoffnungsvolle Festelektrolyte für die Festoxidbrennstoffzelle bei intermediärer Temperatur (IT-SOFC) betrachtet. Normalerweise wird metallisches Nickel zur Herstellung der Komposit-Anode verwendet, wobei neuerdings die Nickelate von Seltenerdmetallen, wie z.B. Sr-dotierte La2NiO4 (LSN), zur Hochleistungskathode entwickelt werden. Um IT-SOFC erfolgreich herzustellen und auszunutzen sind die Kenntnisse der Phasengleichgewichten und Thermodynamik für Systeme notwendig, welche die Kathoden, Festelektrolyt, Anoden und ihre mögliche Kombinationen repräsentieren. Ziel der Arbeit ist die Phasengleichgewichten und Thermodynamik von La-Sr-Ga-Mg-Ni-O, Ce-Gd-Sr-Ni-O und Ce-Gd-La-Ni-O Systeme zu bestimmen. Die Subsysteme wurden thermodynamisch berechnet auf der Basis von Literaturdaten, während die experimentelle Untersuchungen durch berechnete Phasendiagramm entworfen wurden, wodurch weniger Aufwand benötigt wurde. Schließlich wurden die experimentellen und rechnerischen Ergebnisse verwendet, um die Kompatibilität und Reaktivität von IT-SOFC Komponenten unter Herstellung- und Arbeitsbedingungen vorauszusagen. Für die experimentelle Bestimung der Phasengleichgewichte der Systeme wurden verschiedene Untersuchungsmethoden verwendet, wie z.B. Rasterelektronmikroskopie (REM), Energiedispersive Röntgenspektroskopie (EDX), Dynamische Differenzkalorimetrie und Thermogravimetrie. Die CALPHAD-Methode (Calculation of PHAse Diagrams) mit THERMOCALC Software wurde auch verwendet, um eine selbstkonsequente Reihe von freien Enthalpie Funktionen zu bekommen. Die folgenden Systeme wurden experimentell untersucht: La-Ni-O, La-Ga-Ni-O, La-Sr-Ni-O, La-Mg-Ni-O, La-Ga-Mg-Ni-O, La-Sr-Ga-Ni-O, La-Sr-Ga-Mg-Ni-O, Ce-Ni-O, Ce-Sr-O, Gd-Ni-O, Gd-Sr-O, Ce-Gd-Ni-O, Ce-Gd-Sr-O, Ce-Sr-Ni-O, Gd-Sr-Ni-O, Ce-Gd-Sr-Ni-O, Ce-Gd-La-Ni-O. Durch erhaltenen Ergebnisse und Literaturdaten wurden thermodynamische Modelle für die folgenden Systemen gestellt: La-Ni-O, La-Ga-Ni-O, La-Sr-Ni-O, La-Mg-Ni-O, Ce-Ni-O, Ce-Sr-O, Gd-Ni-O, Gd-Sr-O. Mit optimierte Parameter von Systemen niedrigerer Ordnung wurden die Systeme La-Ga-Mg-Ni-O, La-Sr-Ga-Ni-O, und Ce-Gd-Ni-O extrapoliert. Im La-Ni-O System wurden die Bildungsenthalpie, Entropie und Wärmekapazität von La3Ni2O7, La4Ni3O10 und LaNiO3 durch Gleichgewicht mit Gasphase, adiabatische Kalorimetrie und Dynamische Differenzkalorimetrie experimentell bestimmt. In den La-Ga-Ni-O, La-Sr-Ni-O, La-Mg-Ni-O Systeme wurden erweiterten Mischkristalle La(Ga,Ni)O3, La2(Ni,Ga)O4, La4(Ni,Ga)3O10, (La,Sr)2NiO4 und La2(Ni,Mg)O4 gefunden und ihre Homogenitätsbereichen bestimmt. Zusätzlich wurden die Magnetoplumbite-Typ Verbindung LaNiGa11O19 gefunden, die bislang noch nicht in der Literaturen bekannt war. Im La-Ga-Mg-Ni-O System wurde die Temperaturabhängigkeit von La(Ga,Mg,Ni)O3 Homogenitätsbereich untersucht. Im La-Sr-Ga-Ni-O System wurde eine Reaktion zwischen LaGaO3 und LaSrNiO4 untersucht, die Melilite-Typ La1-xSr1+xGa3O7+z, LaGaSrO4 und NiO bildet. Der gleiche Reaktionsmechanismus wurde auch im La-Sr-Ga-Mg-Ni-O System beobachtet. Die Experimente für Ce-Ni-O System wurden sowohl an Luft als auch im Reduktions- Atmosphäre durchgeführt. Es wurde gefunden, dass NiO nicht mit CeO2 reagiert. Für Ce-Sr-O System wurden zuerst die Entropie und Wärmekapazität von Sr2CeO4 experimentell bestimmt. Für Gd-Ni-O System wurde eine eutektische Reaktion (Schmelze <=> B-Gd2O3 + NiO) untersucht. Für das Gd-Sr-O System wurde ein thermodynamisches Modell aus Literaturdaten aufgestellt und auf Gd2O3-reichen Seite die Homogenitätsbereiche experimentell untersucht. Im Ce-Sr-Ni-O System wurde auf SrO-reichen Seite das Mischkristall (Ce,Sr)2NiO4-z untersucht. Es wurde festgestellt, dass keine Reaktion zwischen NiO und SrCeO3 / Sr2CeO4 stattgefunden hat. Im Ce-Gd-Ni-O System wurde keine Reaktion zwischen (Ce,Gd)O2-z und NiO gefunden. Im Ce-Gd-Sr-O System wurden Mischkristalle Sr(Ce,Gd)O3, Sr2(Ce,Gd)O4 und (Gd,Sr)2(Sr,Ce)O4 untersucht. Im Gd-Sr-Ni-O System wurde ein Mischkristall (Gd,Sr)2NiO4 untersucht, der in quasi-binären Schnitten nicht existiert, aber im System höherer Ordnung stabilisiert wird. Es wurde auch gefunden, dass in die Gd2SrO4 Phase keine NiO gelöst wird. Daraus kann man schliessen, dass dotierte Ceroxide (DC) basierte Materialien mit NiO während der Herstellung und Betrieb von IT-SOFC chemisch kompatibel sind, wobei LSGM Elektrolyte unter Herstellungsbedingungen in der Zelle mit NiO reagieren. Obwohl La2NiO4 eine Hochleistungskathode ist, lässt es sich nicht in Kombination mit LSGM oder DC benutzen, weil es mit den beiden Materialien unter Herstellungsbedingungen in der Zelle miteinander reagiert.

The energy expenditure (24h total energy expenditure, TEE) of a healthy individual or a patient is a vital reference point for nutritional therapy to maintain body mass. TEE is usually determined by measuring resting energy expenditure (REE) by indirect calorimetry or by estimation with the help of formulae like the formula of Harris and Benedict with an accuracy of ±20%. Further components of TEE (PAL, DIT) are estimated afterwards. TEE in intensive care patients is generally only 0–7% higher than REE, due to a low PAL and lower DIT. While diseases, like particularly sepsis, trauma and burns, cause a clinically relevant increase in REE between 40–80%, in many diseases, TEE is not markedly different from REE. A standard formula should not be used in critically ill patients, since energy expenditure changes depending on the course and the severity of disease. A clinical deterioration due to shock, severe sepsis or septic shock may lead to a drop of REE to a level only slightly (20%) above the normal REE of a healthy subject. Predominantly immobile patients should receive an energy intake between 1.0–1.2 times the determined REE, while immobile malnourished patients should receive a stepwise increased intake of 1.1–1.3 times the REE over a longer period. Critically ill patients in the acute stage of disease should be supplied equal or lower to the current TEE, energy intake should be increased stepwise up to 1.2 times (or up to 1.5 times in malnourished patients) thereafter. GMS German Medical Science; 7:Doc25; ISSN 1612-3174

The invasion of multiple strains of the midge-borne bluetongue virus into southern Europe since the late 1990s provides a rare example of a clear impact of climate change on a vector-borne disease. However, the subsequent dramatic continent-wide spread and burden of this disease has depended largely on altered biotic interactions with vector and host communities in newly invaded areas. Transmission by Palearctic vectors has facilitated the establishment of the disease in cooler and wetter areas of both northern and southern Europe. This paper discusses the important biological and climatic processes involved in these invasions, and the lessons that must be drawn for effective risk management of bluetongue and other midge-borne viruses in Europe.

We are in a state of climate emergency, and this is also a health emergency. The healthcare system itself is currently a significant producer of carbon emissions, however the NHS has set an ambitious target, committing to net zero by 2045. Reaching this crucial goal will require change not only at an organisational level, but action from every single one of the 1.3 million people working for the NHS. This report recommends system-wide transformational and behavioural change in order for the NHS to reach its net zero target. We have investigated the barriers to sustainability, and have created a number of scalable tools which can be used to better understand obstacles that individuals within then NHS face in implementing sustainability changes. We have also developed guidance on how to use system-wide transformational change to achieve net zero in the NHS, focussing on four key areas: Education & Awareness; Procurement; Progress & Improvement and Communication & Knowledge Sharing. This interactive report brings together the various resources, reflections, tools and recommendations to create a blueprint to inform the development of regional NHS Green Plans and deliver net zero.