Genetics of osteoarthritis.

Osteoarthritis genetics has been transformed in the past decade through the application of large-scale genome-wide association scans. So far, over 100 polymorphic DNA variants have been associated with this common and complex disease. These genetic risk variants account for over 20% of osteoarthritis heritability and the vast majority map to non-protein coding regions of the genome where they are presumed to act by regulating the expression of target genes. Statistical fine mapping, in silico analyses of genomics data, and laboratory-based functional studies have enabled the identification of some of these targets, which encode proteins with diverse roles, including extracellular signaling molecules, intracellular enzymes, transcription factors, and cytoskeletal proteins. A large number of the risk variants correlate with epigenetic factors, in particular cartilage DNA methylation changes in cis, implying that epigenetics may be a conduit through which genetic effects on gene expression are mediated. Some of the variants also appear to have been selected as humans adapted to bipedalism, suggesting that a proportion of osteoarthritis genetic susceptibility results from antagonistic pleiotropy, with risk variants having a positive role in joint formation but a negative role in the long-term health of the joint. Although data from an osteoarthritis genetic study has not yet directly led to a novel treatment, some of the osteoarthritis associated genes code for proteins that have available therapeutics. Genetic investigations are therefore revealing fascinating fundamental insights into osteoarthritis and can expose options for translational intervention.

Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel.

Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5:1 (Standard Rodent Chow), and measured the influence of diet on core body temperature (Tb), brown adipose tissue (BAT) mass, fatty acid profiles of BAT, white adipose tissue (WAT) and plasma as well as hypothalamic endocannabinoid and endocannabinoid-like bioactive fatty acid amides during hibernation. Results show feeding a diet high in omega 3 PUFAs, with a more balanced omega 6:3 ratio, increases AGS Tb in torpor. We found the diet-induced increase in Tb during torpor is most easily explained by an increase in the mass of BAT deposits of Balanced Diet AGS. The increase in BAT mass is associated with elevated levels of metabolites DHA and EPA in tissue and plasma suggesting that these omega 3 PUFAs may play a role in thermogenesis during torpor. While we did not observe diet-induced change in endocannabinoids, we do report altered hypothalamic levels of some endocannabinoids, and endocannabinoid-like compounds, during hibernation.

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC.

OBJECTIVE: In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. This implies that methylation links chondrocyte genotype and phenotype, thus driving the functional effect of this genetic risk signal. PLEC encodes plectin, a cytoskeletal protein that enables tissues to respond to mechanical forces. We sought to assess whether these PLEC functional effects were cartilage specific. METHOD: Cartilage, fat pad, synovium and peripheral blood were collected from patients undergoing arthroplasty. PLEC CpGs were analysed for mQTLs and allelic expression imbalance (AEI) was performed to test for eQTLs. Plectin was knocked down in a mesenchymal stem cell (MSC) line using CRISPR/Cas9 and cells phenotyped by RNA-sequencing. RESULTS: mQTLs were discovered in fat pad, synovium and blood. Their effects were however stronger in the joint tissues and of comparable effect between these tissues. We observed AEI in synovium in the same direction as for cartilage and correlations between methylation and PLEC expression. Knocking-down plectin impacted on pathways reported to have a role in OA, including Wnt signalling, glycosaminoglycan biosynthesis and immune regulation. CONCLUSIONS: Synovium is also a target of the rs11780978 OA association functionally operating on PLEC. In fat pad, mQTLs were identified but these did not correlate with PLEC expression, suggesting the functional effect is not joint-wide. Our study highlights interplay between genetic risk, DNA methylation and gene expression in OA, and reveals clear differences between tissues from the same diseased joint.

Significant cardiac disease complicating Graves' disease in previously healthy young adults.

SUMMARY: Graves' disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy - all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves' disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11-25 pmol/L), fT3: 46.9 (3.1-6.8 pmol/L), TSH <0.01 (0.27-4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves' orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy - EF 10-15%. He partially recovered after treatment - EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly - EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves' disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves' disease relapse and further cardiac decompensation. LEARNING POINTS: Cardiac complications of Graves' disease are uncommon in young adults without previous cardiac disease. These complications may however occur if Graves' disease had been poorly controlled for several weeks or months prior to presentation. Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease. Specific treatment of Graves' disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis. Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.

The impact of male factor infertility on early and late morphokinetic parameters: a retrospective analysis of 4126 time-lapse monitored embryos.

STUDY QUESTION: Is there an effect of male factor infertility (MFI) on either early or late morphokinetic parameters obtained during embryonic culture to blastocyst stage in a time-lapse imaging (TLI) incubator? SUMMARY ANSWER: Neither mild nor severe MFI had an impact on overall time to blastocyst or duration of individual cleavage stages in the total embryo population. WHAT IS KNOWN ALREADY: Prior studies have suggested that paternal DNA and sperm quality affect embryo morphokinetic parameters, but the impact of MFI is not fully understood. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, at a major academic fertility centre, included 536 couples (women, ≤44 years of age) undergoing IVF between September 2013 and September 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 4126 embryos cultured to the blastocyst stage in a TLI-monitored incubator were retrospectively reviewed. Embryos derived from the sperm of men with MFI were compared with those derived from patients with other infertility diagnoses. Generalized fixed and random effects models, t-test and χ2 were used as appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: Couples with MFI had a higher rate of ICSI utilization and fewer usable embryos on average, and the men were older compared with couples with other diagnoses. Additionally, the women in MFI couples were younger and had higher antral follicle counts (AFCs) and higher anti-Müllerian hormone (AMH) levels compared with the other women undergoing IVF. When controlling for maternal and paternal ages, AMH and fertilization method (conventional IVF versus ICSI), neither mild nor severe MFI affected duration of individual cleavage stages or overall time to the blastocyst stage, when all or only usable embryos were examined (coefficient 0.44 hours in all embryos, P = 0.57; coefficient 0.39 hours in usable embryos, P = 0.60). Whether the sperm was surgically extracted similarly had no significant effect on embryo morphokinetic parameters. When the fertilization method was assessed independently, ICSI lengthened the overall time to blastocyst stage by 1.66 hours (P = 0.03) on average, primarily due to an increase in duration of the time from 5-cell embryo stage to early blastulation (P5SB). LIMITATIONS, REASONS FOR CAUTION: This large cohort study avoided embryo selection bias due to random assignment of embryos to the TLI incubators. However, our findings may not be generalizable to groups under-represented in our clinic population. Future studies should also evaluate the impact of male hormonal status and detailed sperm morphology, such as head versus flagellum defects, on embryo morphokinetic development. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that the fertilization method rather than MFI per se impacts time to early blastulation. The clinical implications of this effect on embryo development warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S): There were no sources of funding for this study. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Updated Summation Model: An Improved Agreement with the Daya Bay Antineutrino Fluxes.

A new summation method model of the reactor antineutrino energy spectrum is presented. It is updated with the most recent evaluated decay databases and with our total absorption gamma-ray spectroscopy measurements performed during the last decade. For the first time, the spectral measurements from the Daya Bay experiment are compared with the antineutrino energy spectrum computed with the updated summation method without any renormalization. The results exhibit a better agreement than is obtained with the Huber-Mueller model in the 2-5 MeV range, the region that dominates the detected flux. A systematic trend is found in which the antineutrino flux computed with the summation model decreases with the inclusion of more pandemonium-free data. The calculated flux obtained now lies only 1.9% above that detected in the Daya Bay experiment, a value that may be reduced with forthcoming new pandemonium-free data, leaving less room for a reactor anomaly. Eventually, the new predictions of individual antineutrino spectra for the ^{235}U, ^{239}Pu, ^{241}Pu, and ^{238}U are used to compute the dependence of the reactor antineutrino spectral shape on the fission fractions.

Improved Value for the Gamow-Teller Strength of the

A record number of ^{100}Sn nuclei was detected and new isotopic species toward the proton dripline were discovered at the RIKEN Nishina Center. Decay spectroscopy was performed with the high-efficiency detector arrays WAS3ABi and EURICA. Both the half-life and the ß-decay end point energy of ^{100}Sn were measured more precisely than the literature values. The value and the uncertainty of the resulting strength for the pure 0^{+}→1^{+} Gamow-Teller decay was improved to B_{GT}=4.4_{-0.7}^{+0.9}. A discrimination between different model calculations was possible for the first time, and the level scheme of ^{100}In is investigated further.

Discovery and analysis of methylation quantitative trait loci (mQTLs) mapping to novel osteoarthritis genetic risk signals.

OBJECTIVE: Osteoarthritis (OA) is polygenic with over 90 independent genome-wide association loci so far reported. A key next step is the identification of target genes and the molecular mechanisms through which this genetic risk operates. The majority of OA risk-conferring alleles are predicted to act by modulating gene expression. DNA methylation at CpG dinucleotides may be a functional conduit through which this occurs and is detectable by mapping methylation quantitative trait loci, or mQTLs. This approach can therefore provide functional insight into OA risk and will prioritize genes for subsequent investigation. That was our goal, with a focus on the largest set of OA loci yet to be reported. METHOD: We investigated DNA methylation, genotype and RNA sequencing data derived from the cartilage of patients who had undergone arthroplasty and combined this with in silico analyses of expression quantitative trait loci, epigenomes and chromatin interactions. RESULTS: We investigated 42 OA risk loci and in ten of these we identified 24 CpGs in which methylation correlated with genotype (false discovery rate (FDR) P-values ranging from 0.049 to 1.73x10-25). In silico analyses of these mQTLs prioritised genes and regulatory elements at the majority of the ten loci, with COLGALT2 (encoding a collagen galactosyltransferase), COL11A2 (encoding a polypeptide chain of type XI collagen) and WWP2 (encoding a ubiquitin ligase active during chondrogenesis) emerging as particularly compelling target genes. CONCLUSION: We have highlighted the pivotal role of DNA methylation as a link between genetic risk and OA and prioritized genes for further investigation.

Cryoablation and immunotherapy: an overview of evidence on its synergy.

Cancer cells can escape the immune system by different mechanisms. The evasion of cancer cells from immune surveillance is prevented by immune checkpoint inhibitors, allowing the patient's own immune system to attack their cancer. Immune checkpoint inhibitors have shown improvement in overall survival for melanoma, lung cancer and renal cell carcinoma in clinical trials. Unfortunately, not all patients respond to this therapy.In cancer management, percutaneous ablation techniques are well established for both cure and local control of many tumour types. Cryoablation of the tumour tissue results in cell destruction by freezing. Contrary to heat-based ablative modalities, cryoablation induces tumour cell death by osmosis and necrosis. It is hypothesised that with necrosis, the intracellular contents of the cancer cells stay intact allowing the immune system to induce an immune-specific reaction. This immune-specific reaction can, in theory, also affect cancer cells outside the ablated tissue, known as the abscopal effect. Unfortunately, this effect is rarely observed, but when cryoablation is combined with immunotherapy, the effect of both therapies may be enhanced. Although several preclinical studies demonstrated a synergistic effect between cryoablation and immunotherapy, prospective clinical trials are needed to prove this clinical benefit for patients. In this review, we will outline the current evidence for the combination of cryoablation with immunotherapy to treat cancer.

Towards Neutron Capture on Exotic Nuclei: Demonstrating (d,pγ) as a Surrogate Reaction for (n,γ).

The neutron-capture reaction plays a critical role in the synthesis of the elements in stars and is important for societal applications including nuclear power generation and stockpile-stewardship science. However, it is difficult-if not impossible-to directly measure neutron capture cross sections for the exotic, short-lived nuclei that participate in these processes. In this Letter we demonstrate a new technique which can be used to indirectly determine neutron-capture cross sections for exotic systems. This technique makes use of the (d,p) transfer reaction, which has long been used as a tool to study the structure of nuclei. Recent advances in reaction theory, together with data collected using this reaction, enable the determination of neutron-capture cross sections for short-lived nuclei. A benchmark study of the ^{95}Mo(d,p) reaction is presented, which illustrates the approach and provides guidance for future applications of the method with short-lived isotopes produced at rare isotope accelerators.

Cardiovascular risk assessments at occupational health services: employee experiences.

BACKGROUND: Across England in the UK, population screening for cardiovascular disease (CVD) primarily takes place within general practice in the form of the National Health Service Health Check. Additional screening sites such as occupational health are advocated to improve the population impact. AIMS: To investigate participant experiences with cardiovascular and type 2 diabetes risk assessment (RA) at occupational health and subsequent support-seeking at general practice. METHODS: Face-to-face interviews were conducted for this qualitative study. Participants were recruited at three workplaces; a steel works and two hospital sites. Using interpretive phenomenological analyses, themes were drawn from salient narratives and categorically organized. RESULTS: There were 29 participants. Themes (n = 16) were organized into two domains; factors that facilitated (n = 9) or thwarted (n = 7) participant engagement with the RA and general practice. All participants described the RA as worthwhile and strongly valued RA at occupational health. Those with obesity and high CVD risk highlighted their difficulties in making lifestyle changes. Participants reported confusion and anxiety when GP advice about medication appeared to contradict what participants had interpreted during RA at occupational health. CONCLUSIONS: This study highlights factors that facilitate or thwart engagement in cardiovascular RA at occupational health services and general practice follow-up. Stakeholders can integrate these factors into standard operating procedures to enhance participant engagement and enable safeguards that minimize potential harm to participants.

Fabricated facial rash - an unusual presentation of factitious disorder.

Patients with factitious disorder typically present with signs or symptoms suggesting a medical problem, but which transpire to be self-induced or fabricated. Repeated investigations and treatments are often carried out to no avail before this possibility is considered. In this case, a 51-year-old female presented to the oral and maxillofacial surgery unit with toothache and a facial rash. Following admission to hospital a range of investigations were performed, and a tooth was extracted. Judicious attention by nursing staff led to the discovery that the patient had been applying make-up to mimic a skin rash. This concern was raised with the patient and she admitted falsifying the rash. Although this patient may have been experiencing pain, by applying make-up in this manner she sought to exaggerate the severity of her condition and as a result underwent potentially unnecessary procedures. This case provides a reminder that the possibility of factitious disorder should be considered in cases where patients present with symptoms or signs which appear fabricated or self-inflicted, defy anatomical or physiological principles, or do not correlate with the history. Thorough history taking is essential, and access to electronic care records may be informative. Psychiatric follow-up is recommended, but not all patients are willing to engage with this process.

Enhancing social functioning in young people at Ultra High Risk (UHR) for psychosis: A pilot study of a novel strengths and mindfulness-based online social therapy.

BACKGROUND: Psychological and pharmacological treatments have been shown to reduce rates of transition to psychosis in Ultra High Risk (UHR) young people. However, social functioning deficits have been unresponsive to current treatments. AIMS: The study aims were to: i) describe the theoretical basis and therapeutic targets of a novel intervention targeting social functioning in UHR young people; and ii) examine its acceptability, safety and preliminary effect on social functioning. METHODS: An international, multidisciplinary team developed a new intervention (MOMENTUM) to improve social functioning in UHR young people. MOMENTUM blends two novel approaches to social recovery: strengths and mindfulness-based intervention embedded within a social media environment, and application of the self-determination theory of motivation. The acceptability and safety of MOMENTUM were tested through a 2-month pilot study with 14 UHR participants. RESULTS: System usage was high, with over 70% of users being actively engaged over the trial. All participants reported a positive experience using MOMENTUM, considered it safe and would recommend it to others. 93% reported it to be helpful. There were large, reliable improvements in social functioning (d = 1.83, p < 0.001) and subjective wellbeing (d = 0.75, p = 0.03) at follow-up. There were significant increases in the mechanisms targeted by the intervention including strengths usage (d = 0.70, p = 0.03), mindfulness skills (d = 0.66, p = 0.04) and components of social support. Social functioning improvement was significantly correlated with indicators of system usage. CONCLUSION: MOMENTUM is engaging and safe. MOMENTUM appeared to engage the hypothesized mechanisms and showed promise as a new avenue to improve social functioning in UHR young people.

Interventional management of hyperhidrosis in secondary care: a systematic review.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating, which occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. OBJECTIVES: To undertake a systematic review of the clinical effectiveness and safety of treatments available in secondary care for the management of primary hyperhidrosis. METHODS: Fifteen databases (including trial registers) were searched to July 2016 to identify studies of secondary-care treatments for primary hyperhidrosis. For each intervention randomized controlled trials (RCTs) were included where available; where RCT evidence was lacking, nonrandomized trials or large prospective case series were included. Outcomes of interest included disease severity, sweat rate, quality of life, patient satisfaction and adverse events. Trial quality was assessed using a modified version of the Cochrane Risk of Bias tool. Results were pooled in pairwise meta-analyses where appropriate, otherwise a narrative synthesis was presented. RESULTS: Fifty studies were included in the review: 32 RCTs, 17 nonrandomized trials and one case series. The studies varied in terms of population, intervention and methods of outcome assessment. Most studies were small, at high risk of bias and poorly reported. The interventions assessed were iontophoresis, botulinum toxin (BTX) injections, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland. CONCLUSIONS: The evidence for the effectiveness and safety of treatments for primary hyperhidrosis is limited overall, and few firm conclusions can be drawn. However, there is moderate-quality evidence to support the use of BTX for axillary hyperhidrosis. A trial comparing BTX with iontophoresis for palmar hyperhidrosis is warranted.

Mesoscopic Energy Minimization Drives Pseudomonas aeruginosa Biofilm Morphologies and Consequent Stratification of Antibiotic Activity Based on Cell Metabolism.

Segregation of bacteria based on their metabolic activities in biofilms plays an important role in the development of antibiotic resistance. Mushroom-shaped biofilm structures, which are reported for many bacteria, exhibit topographically varying levels of multiple drug resistance from the cap of the mushroom to its stalk. Understanding the dynamics behind the formation of such structures can aid in design of drug delivery systems, antibiotics, or physical systems for removal of biofilms. We explored the development of metabolically heterogeneous Pseudomonas aeruginosa biofilms using numerical models and laboratory knockout experiments on wild-type and chemotaxis-deficient mutants. We show that chemotactic processes dominate the transformation of slender and hemispherical structures into mushroom structures with a signature cap. Cellular Potts model simulation and experimental data provide evidence that accelerated movement of bacteria along the periphery of the biofilm, due to nutrient cues, results in the formation of mushroom structures and bacterial segregation. Multidrug resistance of bacteria is one of the most threatening dangers to public health. Understanding the mechanisms of the development of mushroom-shaped biofilms helps to identify the multidrug-resistant regions. We decoded the dynamics of the structural evolution of bacterial biofilms and the physics behind the formation of biofilm structures as well as the biological triggers that produce them. Combining in vitro gene knockout experiments with in silico models showed that chemotactic motility is one of the main driving forces for the formation of stalks and caps. Our results provide physicists and biologists with a new perspective on biofilm removal and eradication strategies.

Who let the dogs out? Therapy dogs in clinical practice.

OBJECTIVES: Animal-assisted therapy (AAT) is a growing field in Australia, and therapy dogs are becoming increasingly common in clinical settings. This paper aims to highlight the current issues facing AAT in Australia and to make recommendations on how to progress the field. We acknowledge that there are several ways that therapy dogs may enhance treatment outcomes for clients, such as reductions in stress and acute anxious arousal, and improvements in engagement and rapport. These psychological and physiological advantages, however, may not be sustained once interaction with the dog ceases. Clinicians require adequate training and support to develop and implement interventions that are based on sound theoretical foundations, and take advantage of the adjunctive benefits of animal presence. CONCLUSIONS: A series of recommendations are made for the professionalisation of AAT, including the development of consensus definitions, clinical governance, accreditation, research and evaluation.

How do oral and maxillofacial surgeons manage concussion?

Craniofacial trauma results in distracting injuries that are easy to see, and as oral and maxillofacial surgeons (OMFS) we gravitate towards injuries that can be seen and are treatable surgically. However, we do tend not to involve ourselves (and may potentially overlook) injuries that are not obvious either visually or radiographically, and concussion is one such. We reviewed the records of 500 consecutive patients who presented with facial fractures at the Queen Elizabeth Hospital, Birmingham, to identify whether patients had been screened for concussion, and how they had been managed. Of the 500 cases 186 (37%) had concussion, and 174 (35%) had a more severe traumatic brain injury. The maxillofacial team documented loss of consciousness in 314 (63%) and pupillary reactions in 215 (43%). Ninety-three (19%) were referred for a neurosurgical opinion, although most of these were patients who presented with a Glasgow coma scale (GCS) of ≤13. Only 37 patients (7%) were referred to the traumatic brain injury clinic. Recent reports have indicated that 15% of all patients diagnosed with concussion have symptoms that persist for longer than two weeks. These can have far-reaching effects on recovery, and have an appreciable effect on the psychosocial aspects of the patients' lives. As we have found, over one third of patients with craniofacial trauma are concussed. We think, therefore, that all patients who have been referred to OMFS with craniofacial trauma should be screened for concussion on admission, and at the OMFS follow up clinic. In addition, there should be an agreement between consultants that such patients should be referred to the traumatic brain injury clinic for follow up.

Discovery of

In this Letter, the observation of two previously unknown isotopes is presented for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive an upper limit for the ground-state half-life of 81 ns, consistent with the previous upper limit of 30 ns. For ^{72}Rb, we have measured a half-life of 103(22) ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb, with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The ^{72}Rb half-life is consistent with a 5^{+}→5/2^{-} proton decay with an energy of 800-900 keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)→9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.