Caregiver experiences of hospice dementia care: a systematic review and meta-ethnography.

OBJECTIVES: Hospices are regarded as gold standard providers of end-of-life care. The term hospice, however, is broadly used, and can describe a type of care offered in a variety of health care services (e.g. nursing homes). It thus becomes complex for families to decide between services. We aimed to review the evidence around the experience of family carers of people with dementia accessing in-patient hospice settings for end-of-life care. METHOD: We registered the review protocol on PROSPERO. We used PerSPE(C)TiF to systematically organise our search strategy. The evidence was reviewed across six databases: PubMed, EMBASE, PsycINFO, ASSIA, ISI Web, and CINAHL. We used meta-ethnography as per the eMERGe guidance for data interpretation. RESULTS: Four studies were included. Two third-order constructs were generated through meta-ethnography: expectations of care and barriers to quality of care. We found that carers had expectations of care, and these could change over time. If discussion was not held with hospice staff early on, the carers could experience reduced care quality due to unmatched expectations. Unmatched expectations acted as barriers to care and these were found in terms of carers not feeling adequately supported, and/or having the person discharged from hospice, which would entail increased care responsibility for carers. CONCLUSION: In view of an increase in new dementia cases over time and with hospice services being under pressure, integrating palliative care services within community-based models of care is key to reducing the risk of having inadequate and under resourced services for people with dementia.

From compost to culver: genome sequence and annotation of a cluster CQ1 Gordonia phage.

Phage Culver, with a siphovirus morphology, was isolated using Gordonia terrae CAG3. Culver is assigned to phage cluster CQ1 based on gene content similarity to actinobacteriophages. Notably, Culver is predicted to encode eight tRNAs, lysin A by two adjacent genes, and, unlike other CQ1 phages, two putative integrase genes.

The association and reliability of the frontal plane projection angle during the lateral step down test on knee function in patients with patellofemoral pain.

BACKGROUND: The lateral step-down test is used by physical therapists (PT) to identify movement faults in patients with patellofemoral pain (PFP). The FPPA is a measure of knee valgus and PTs have access to open source video analysis software and high quality smart phones and video cameras to implement 2D video analysis into practice. The purpose of our study was to determine the reliability of PTs measuring the frontal plane projection angle (FPPA) during the lateral step-down test, and to determine if the FPPA was associated with pain, self-reported knee function and fear of movement. METHODS: Twenty-two subjects (mean age[SD] = 27.8 [6.6] years, females n = 14, males n = 8) with PFP were analyzed by six PTs using 2D video analysis software. The FPPA was measured during the lateral step down test. Numeric Pain Rating Scale (NPRS), Anterior Knee Pain Scale (AKPS) and the Tampa Scale of Kinesiophobia (TSK) were collected. Intraclass correlation (ICC) was used to assess for PT measurement reliability. Correlations between outcomes were calculated using Spearman correlation coefficient and standard error of measurement (SEM) and minimal detectable change (MDC) were reported. RESULTS: Reliability amongst PTs measuring the FPPA was good (ICC [95 %CI] = 0.85 [0.72-0.93]; SEM = 3.33°, MDC = 9.20°). There were no significant correlations (p > 0.05) between FPPA and NPRS(ρ = -0.046), AKPS(ρ = 0.066), or TSK(ρ = -0.204). CONCLUSIONS: Although reliability measuring FPPA was good, the large SEM and MDC associated with this measurement may limit its clinical utility in those with PFP.

Prevalence, geographic distribution, and impact on lifespan of a dilated cardiomyopathy-associated RNA-binding motif protein 20 variant in genotyped dogs.

INTRODUCTION: The study objectives were to determine the prevalence and geographic distribution of a dilated cardiomyopathy (DCM)-associated RNA-binding motif protein 20 (RBM20) variant in canine DNA samples submitted for testing and to evaluate the influence of the genotype on cardiac phenotype and lifespan. ANIMALS: Samples from 2136 dogs including 1834 Standard Schnauzers (SSNZ), 266 Giant Schnauzers (GSNZ), and 36 dogs of other breeds. METHODS: The University of Missouri Canine Genetics Laboratory's sample-accession spreadsheet and Orthopedic Foundation for Animals' database were retrospectively reviewed for samples submitted for RBM20 genotyping from November, 2013, through May, 2018. Data analyzed included breed, date of birth, RBM20 genotype (homozygous wild-type, heterozygous variant [HET], or homozygous variant [HOM]), geographic origin of submission, pedigree, cardiac phenotype, and date of death or current age if alive. RESULTS AND DISCUSSION: The RBM20 variant was only detected in SSNZ and GSNZ. A total of 389 SSNZ were variant-positive (prevalence = 21.2%), with 361 HET (19.7%) and 28 HOM (1.5%). Of the HOM SSNZ, DCM was confirmed in 26 of 28 (92.9%), with the remainder lost to follow-up. The median lifespan of HOM SSNZ (3.06 years) was significantly shorter than that for HET (15.11 years) and wild-type (15.18 years) SSNZ. Twenty-six GSNZ were variant-positive (prevalence = 9.8%), with 23 HET (8.6%) and three HOM (1.1%). Nine GSNZ belonged to one family, including the three HOM GSNZ that all had DCM. CONCLUSIONS: The HOM genotype is associated with DCM and premature death in SSNZ and GSNZ.

Factors influencing time to return to sport following clavicular fractures in adolescent athletes.

BACKGROUND: There is a trend toward increased surgical treatment of displaced clavicle fractures in the adolescent population presumably because of extrapolation of adult-derived best practice guidelines. The purpose of this study was to compare return to sport between nonoperative and operative treatment of clavicle fractures in high school athletes. METHODS: A retrospective review of clavicle fractures sustained in scholastic athletes participating in school-sponsored athletics in the upstate South Carolina was performed from 2015 to 2019. Injury circumstances, demographics, radiographs, treatment, and return to sport data were documented for all patients. Radiographs were evaluated for fracture location, comminution, displacement, shortening, and angulation. Patients were followed until complete return to sport, and results were compared based on sport participation, injury mechanism, fracture morphology, treatment type, and time to return to sport. RESULTS: Forty-seven patients (44 were male; average age 15.6 years) were included who all returned to sport within the original or subsequent season. Thirty-six patients (73%) were managed conservatively (30 middle third fractures, 4 medial third fractures, 2 distal third fractures), whereas 11 were managed surgically (11 middle third fractures). Eighty-one percent of fractures occured in collision athletes (55% in football). There was no difference in time loss based on participating in collision vs. noncontact sports (P = .4). Conservatively managed fractures returned to sport faster (61 ± 38 days vs. 100 ± 49 days; P = .008) compared with surgically managed patients. Fracture displacement ≥100% (100 ± 51 days vs. 54 ± 27 days; P = .001), greater comminution (128 ± 50 days vs. 59 ± 31 days; P = .001), and angulation (86 ± 52 days vs. 54 ± 22 days; P = .001) all were statistically significant for slower return to sport. Athletes presenting with clavicular shortening <2 cm returned to sport within a similar time frame as athletes with ≥2 cm (P = 0.1). CONCLUSION: Our results show that adolescent athletes with clavicular fractures predictably return to athletics, including collision sports. Athletes conservatively managed returned 40% faster than those with surgery. However, this appears to be associated with the severity and complexity of fractures treated surgically. This study provides evidence to counsel adolescent athletes following clavicular fractures on return to sport expectations.

A bright γ-ray flare interpreted as a giant magnetar flare in NGC 253.

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.

Rapid spectral variability of a giant flare from a magnetar in NGC 253.

Magnetars are neutron stars with extremely strong magnetic fields (1013 to 1015 gauss)1,2, which episodically emit X-ray bursts approximately 100 milliseconds long and with energies of 1040 to 1041 erg. Occasionally, they also produce extremely bright and energetic giant flares, which begin with a short (roughly 0.2 seconds), intense flash, followed by fainter, longer-lasting emission that is modulated by the spin period of the magnetar3,4 (typically 2 to 12 seconds). Over the past 40 years, only three such flares have been observed in our local group of galaxies3-6, and in all cases the extreme intensity of the flares caused the detectors to saturate. It has been proposed that extragalactic giant flares are probably a subset7-11 of short γ-ray bursts, given that the sensitivity of current instrumentation prevents us from detecting the pulsating tail, whereas the initial bright flash is readily observable out to distances of around 10 to 20 million parsecs. Here we report X-ray and γ-ray observations of the γ-ray burst GRB 200415A, which has a rapid onset, very fast time variability, flat spectra and substantial sub-millisecond spectral evolution. These attributes match well with those expected for a giant flare from an extragalactic magnetar12, given that GRB 200415A is directionally associated13 with the galaxy NGC 253 (roughly 3.5 million parsecs away). The detection of three-megaelectronvolt photons provides evidence for the relativistic motion of the emitting plasma. Radiation from such rapidly moving gas around a rotating magnetar may have generated the rapid spectral evolution that we observe.

Gamma-Ray and Radio-Frequency Radiation from Thunderstorms Observed from Space and Ground.

Terrestrial gamma ray flashes (TGFs) are a class of enigmatic electrical discharges in the Earth's atmosphere. In this study, we analyze an unprecedentedly large dataset comprised of 2188 TGFs whose signatures were simultaneously measured using space- and ground-based detectors over a five-year period. The Gamma-ray Burst Monitor (GBM) on board the Fermi spacecraft provided the energetic radiation measurements. Radio frequency (RF) measurements were obtained from the Global Lightning Dataset (GLD360). Here we show the existence of two categories of TGFs - those that were accompanied by quasi-simultaneous electromagnetic pulses (EMPs) detected by the GLD360 and those without such simultaneous EMPs. We examined, for the first time, the dependence of the TGF-associated EMP-peak-amplitude on the horizontal offset distance between the Fermi spacecraft and the TGF source. TGFs detected by the GBM with sources at farther horizontal distances are expected to be intrinsically brighter and were found to be associated with EMPs having larger median peak-amplitudes. This provides independent evidence that the EMPs and TGFs are produced by the same phenomenon, rather than the EMPs being from "regular" lightning in TGF-producing thunderstorms.

Safety of dry needling to the upper lumbar spine: a pilot cadaver study.

Objective: When inserting a dry needle laterally into the upper lumbar spine (L1-L3) there is an increased risk of piercing the kidney; therefore, the objective of this study was to determine a zone of safety for practitioners to needle in the upper lumbar spine.Methods: Ten cadavers were screened for inclusion. L1 spinous process was identified and confirmed with ultrasound imaging. A digital caliper was used to measure laterally at 1.5 cm, 2.0 cm, and 2.5 cm. Dry needles were inserted maximally at each point and a binary decision, yes or no, was made to determine if bony contact was made. Needle depth and abdominal width measurements were also recorded. Safety of the dry needling procedure was interpreted as such if bony contact was made by the needle. If bony contact was made, then it was assumed that the needle cannot advance further into pleura or kidney.Results: Forty-four percent of needles did not make bony contact at 2.5 cm lateral of the L1 spinous process, whereas 22% did not make bony contact at 1.5 cm and 2.0 cm. There was a weak to moderate negative correlation between abdominal width measurements and needle depth at 1.5 cm (-0.48) and 2.0 cm (-0.45), and at 2.5 cm (-0.39).Conclusion: A safety zone of needling less than 2.5 cm is likely safe, but needs to be confirmed with future study. Dry needling 2.5 cm lateral appears more risky due to the higher frequency of not contacting a bony backdrop.

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Peri-operative management of ophthalmic patients on anti-thrombotic agents: a literature review.

There is variability in the management of ophthalmic patients on anti-thrombotic agents (antiplatelets and anticoagulants) during the peri-operative period. A survey carried out in a UK teaching hospital on a cohort of ophthalmologists showed majority were comfortable with antiplatelet management but there was variability in managing patients on warfarin and direct oral anticoagulants (DOACs); 40% were unaware of existing guidelines. We aim to review the recommendations in the literature with regards to managing anti-thrombotic agents during the peri-operative period of ophthalmic surgery. We reviewed incidences of complications, specifically, the haemorrhagic complications associated. Pubmed search was carried out on relevant keywords from January 2007 to August 2017. All relevant UK guidelines including the Royal College of Ophthalmologists and British Society of Haematology were reviewed. Literature recommendations for routine cataract surgery under topical or sub-Tenon's anaesthesia would be to continue all anti-thrombotic agents. For sharp needle anaesthesia, avoidance of dual antiplatelet therapy was recommended and warfarin could be continued if INR within therapeutic range. Recommendations for surgeries in glaucoma, vitreo-retinal, oculoplastic and lacrimal; and strabismus are presented. No evidence was found for corneal surgery. Haemorrhagic complications are reported in all groups. Limitations of this review include the retrospective nature, lack of randomized control trials and the limited evidence regarding DOACs. It is important for ophthalmologists to be aware of and balance the risk of thromboembolic events and risks of haemorrhagic complications for ophthalmic surgery. A multi-disciplinary approach is recommended for complex cases.

Traumatic Brachial Plexopathy in Athletes: Current Concepts for Diagnosis and Management of Stingers.

Traumatic upper trunk brachial plexopathy, also known as a stinger or burner, is the most common upper extremity neurologic injury among athletes and most commonly involves the upper trunk. Recent studies have shown the incidence of both acute and recurrent injuries to be higher in patients with certain anatomic changes in the cervical spine. In addition, despite modern awareness, tackling techniques, and protective equipment, some think the incidence to be slowly on the rise in contact athletes. The severity of neurologic injury varies widely but usually does not result in significant loss of playing time or permanent neurologic deficits if appropriate management is undertaken. Timely diagnosis allows implementation of means to minimize the risk of recurrent injury. It is important for treating physicians to understand the pathogenesis, evaluation, and acute and long-term management of stingers to improve recovery and minimize chronic sequela.

Mesencephalic astrocyte-derived neurotropic factor is an important factor in chondrocyte ER homeostasis.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein that can be secreted due to an imperfect KDEL motif. MANF plays a cytoprotective role in several soft tissues and is upregulated in conditions resulting from intracellular retention of mutant protein, including two skeletal diseases, metaphyseal chondrodysplasia, Schmid type (MCDS) and multiple epiphyseal dysplasia (MED). The role of MANF in skeletal tissue homeostasis is currently unknown. Interestingly, cartilage-specific deletion of Manf in a mouse model of MED resulted in increased disease severity, suggesting its upregulation may be chondroprotective. Treatment of MED chondrocytes with exogenous MANF led to a decrease in the cellular levels of BiP (GRP78), confirming MANF's potential to modulate ER stress responses. However, it did not alleviate the intracellular retention of mutant matrilin-3, suggesting that it is the intracellular MANF that is of importance in the pathobiology of skeletal dysplasias. The Col2Cre-driven deletion of Manf from mouse cartilage resulted in a chondrodysplasia-like phenotype. Interestingly, ablation of MANF in cartilage did not have extracellular consequences but led to an upregulation of several ER-resident chaperones including BiP. This apparent induction of ER stress in turn led to dysregulated chondrocyte apoptosis and decreased proliferation, resulting in reduced long bone growth. We have previously shown that ER stress is an underlying disease mechanism for several skeletal dysplasias. The cartilage-specific deletion of Manf described in this study phenocopies our previously published chondrodysplasia models, further confirming that ER stress itself is sufficient to disrupt skeletal growth and thus represents a potential therapeutic target.

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

High-throughput discovery of organic cages and catenanes using computational screening fused with robotic synthesis.

Supramolecular synthesis is a powerful strategy for assembling complex molecules, but to do this by targeted design is challenging. This is because multicomponent assembly reactions have the potential to form a wide variety of products. High-throughput screening can explore a broad synthetic space, but this is inefficient and inelegant when applied blindly. Here we fuse computation with robotic synthesis to create a hybrid discovery workflow for discovering new organic cage molecules, and by extension, other supramolecular systems. A total of 78 precursor combinations were investigated by computation and experiment, leading to 33 cages that were formed cleanly in one-pot syntheses. Comparison of calculations with experimental outcomes across this broad library shows that computation has the power to focus experiments, for example by identifying linkers that are less likely to be reliable for cage formation. Screening also led to the unplanned discovery of a new cage topology-doubly bridged, triply interlocked cage catenanes.

Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre.

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.

Asymptomatic Corneal Keratopathy Secondary to Hypertyrosinaemia Following Low Dose Nitisinone and a Literature Review of Tyrosine Keratopathy in Alkaptonuria.

Nitisinone, although unapproved for use in alkaptonuria (AKU), is currently the only homogentisic acid lowering therapy with a potential to modify disease progression in AKU. Therefore, safe use of nitisinone off-label requires identifying and managing tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular pain and visual impairment and how to manage them. On his first and second annual follow-up visits to the National Alkaptonuria Centre (NAC), there was no corneal keratopathy on slit lamp examination. On his third follow-up annual visit to the NAC, he was found to have typical dendritiform corneal keratopathy in both eyes which was asymptomatic. Nitisinone was suspended until a repeat slit lamp examination, 2 weeks later, confirmed that the keratopathy had resolved. He recommenced nitisinone 2 mg daily with a stricter low protein diet. On his fourth annual follow-up visit to the NAC, a routine slit lamp examination showed mild corneal keratopathy in the left eye. This is despite him reporting no ocular symptoms. This case highlights the fact that corneal keratopathy can occur without symptoms and any monitoring plan with off-label use of nitisinone in AKU will need to take this possibility into account. This is also the first time that typical corneal keratopathy has been described with the use of low dose nitisinone in AKU without symptoms.

Unusual presentation of failed metal-on-metal total hip arthroplasty with features of neoplastic process.

Metal-on-metal (MoM) total hip arthroplasty (THA) is associated with increased incidence of failure from metallosis, adverse tissue reactions, and the formation of pseudotumors. This case highlights a 53-year-old female with an enlarging painful thigh mass 12 years status post MoM THA. Radiographs and advanced imaging revealed an atypical mass with cortical bone destruction and spiculation, concerning for periprosthetic malignancy. Open frozen section biopsy was performed before undergoing revision THA in a single episode of care. This case illustrates that massive pseudotumors can be locally aggressive causing significant femoral bone destruction and may mimic malignancy. It is important that orthopaedic surgeons, radiologists and pathologists understand the relative infrequency of periprosthetic malignancy in MoM THA to mitigate patient concerns, misdiagnosis, and allow for an evidence based discussion when treating massive pseudotumors.

Chirality as a tool for function in porous organic cages.

The control of solid state assembly for porous organic cages is more challenging than for extended frameworks, such as metal-organic frameworks. Chiral recognition is one approach to achieving this control. Here we investigate chiral analogues of cages that were previously studied as racemates. We show that chiral cages can be produced directly from chiral precursors or by separating racemic cages by co-crystallisation with a second chiral cage, opening up a route to producing chiral cages from achiral precursors. These chiral cages can be cocrystallized in a modular, 'isoreticular' fashion, thus modifying porosity, although some chiral pairings require a specific solvent to direct the crystal into the desired packing mode. Certain cages are shown to interconvert chirality in solution, and the steric factors governing this behavior are explored both by experiment and by computational modelling.

Applications of Mass Spectrometry Imaging to Cancer.

Pathologists play an essential role in the diagnosis and prognosis of benign and cancerous tumors. Clinicians provide tissue samples, for example, from a biopsy, which are then processed and thin sections are placed onto glass slides, followed by staining of the tissue with visible dyes. Upon processing and microscopic examination, a pathology report is provided, which relies on the pathologist's interpretation of the phenotypical presentation of the tissue. Targeted analysis of single proteins provide further insight and together with clinical data these results influence clinical decision making. Recent developments in mass spectrometry facilitate the collection of molecular information about such tissue specimens. These relatively new techniques generate label-free mass spectra across tissue sections providing nonbiased, nontargeted molecular information. At each pixel with spatial coordinates (x/y) a mass spectrum is acquired. The acquired mass spectrums can be visualized as intensity maps displaying the distribution of single m/z values of interest. Based on the sample preparation, proteins, peptides, lipids, small molecules, or glycans can be analyzed. The generated intensity maps/images allow new insights into tumor tissues. The technique has the ability to detect and characterize tumor cells and their environment in a spatial context and combined with histological staining, can be used to aid pathologists and clinicians in the diagnosis and management of cancer. Moreover, such data may help classify patients to aid therapy decisions and predict outcomes. The novel complementary mass spectrometry-based methods described in this chapter will contribute to the transformation of pathology services around the world.